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• Oscillatory markers of sleep need are atheoretical; they vary with time awake but cannot inform on the nature of sleep need. • Increasing sleep need relates to excitability in neuronal populations, as may be measured via aperiodic EEG activity. • We discuss the use of aperiodic EEG in measuring sleep need, as well as other issues in using EEG to measure sleep need. Sleep is a daily experience across humans and other species, yet our understanding of how and why we sleep is presently incomplete. This is particularly prevalent in research examining the neurophysiological measurement of sleepiness in humans, where several electroencephalogram (EEG) phenomena have been linked with prolonged wakefulness. This leaves researchers without a solid basis for the measurement of homeostatic sleep need and complicates our understanding of the nature of sleep. Recent theoretical and technical advances may allow for a greater understanding of the neurobiological basis of homeostatic sleep need: this may result from increases in neuronal excitability and shifts in excitation/inhibition balance in neuronal circuits and can potentially be directly measured via the aperiodic component of the EEG. Here, we review the literature on EEG-derived markers of sleepiness in humans and argue that changes in these electrophysiological markers may actually result from neuronal activity represented by changes in aperiodic markers. We argue for the use of aperiodic markers derived from the EEG in predicting sleepiness and suggest areas for future research based on these. [ABSTRACT FROM AUTHOR]

[Display omitted] • Focal cortical cooling altered somatosensory evoked potentials (SEPs). • SEP amplitude was negatively correlated with cortical temperatures of 27.5−38.0 °C. • GABA A R but not AMPAR nor NMDAR antagonists eliminated the negative correlation. • GABAergic signaling is involved in the temperature dependency of SEPs. Although the focal brain cooling technique is widely used to examine brain function, the effects of cortical temperature at various levels on sensory information processing and neural mechanisms remain underexplored. To elucidate the mechanisms of temperature modulation in somatosensory processing, this study aimed to examine how P1 and N1 deflections of somatosensory evoked potentials (SEPs) depend on cortical temperature and how excitatory and inhibitory inputs contribute to this temperature dependency. SEPs were generated through electrical stimulation of the contralateral forepaw in anesthetized rats. The SEPs were recorded while cortical temperatures were altered between 17–38 °C either without any antagonists, with a gamma-aminobutyric acid type A (GABA A) receptor antagonist (gabazine), with an aminomethylphosphonic acid (AMPA) receptor antagonist (NBQX), or with an N -Methyl-D-aspartic acid (NMDA) receptor antagonist ([R]-CPP). The effects of different gabazine concentrations (0, 1, and 10 µM) were examined in the 35–38 °C range. The P1/N1 amplitudes and their peak-to-peak differences plotted against cortical temperature showed an inverted U relationship with a maximum at approximately 27.5 °C when no antagonists were administered. The negative correlation between these amplitudes and temperatures of ≥ 27.5 °C plateaued after gabazine administration, which occurred progressively as the gabazine concentration increased. In contrast, the correlation remained negative after the administration of NBQX and (R)-CPP. These results suggest that GABAergic inhibitory inputs contribute to the negative correlation between SEP amplitude and cortical temperature around the physiological cortical temperature. [ABSTRACT FROM AUTHOR]

• The effect of enactment encoding on subsequent testing effect was investigated. • Enactment encoding had no significant additive effect on the testing effect. • The SPT group exhibited a parietal positivity during the restudy task. • The tested and restudied items elicited a similar positivity in the SPT group. • Enactment encoding and subsequent testing may be redundant in improving memory. Testing is more beneficial for memory retention than restudying the same content. However, the effect of the initial encoding method on the testing effect remains unclear. In this study, a classical testing effect paradigm was employed, along with event-related potentials (ERP), to investigate the electrophysiological processes underlying the effect of enactment encoding on the testing effect. Participants were randomly assigned to the Self-Performed Test (SPT) or Verbalized Test (VT) groups. Both groups underwent three stages: an initial encoding phase, an initial test phase (comprising a source memory task and a restudy task), and a final test phase. During the initial encoding phase, the SPT group encoded action phrases through enactment, while the VT group encoded information through reading. During the initial test phase, the SPT group exhibited superior recognition performance in item memory compared with the VT group. Both groups exhibited significant parietal old/new effects in the source memory task, with only the SPT group displaying parietal positivity during the restudy task. During the final test phase, the behavioral testing effect was exclusively observed in the VT group. Furthermore, the VT group displayed a more pronounced parietal positivity in the test condition compared to the restudy condition, while the parietal positivity between the two conditions was comparable in the SPT group. In summary, the absence of a final behavioral testing effect in the SPT group may be attributed to both enactment and testing primarily enhancing memory performance through recollection-based retrieval, as indicated by the parietal positivity. Consequently, the initial enactment encoding method leaves limited scope for further improvements through subsequent testing. These findings suggest that initial enactment encoding, and subsequent testing may be redundant in improving episodic memory performance. [ABSTRACT FROM AUTHOR]

• Multi-site local field potential (LFPs) was used to study the acute and chronic changes in electrophysiology, functional connectivity, and brain network characteristics with lateral habenula (LHb) as the key target during the formation of chronic constraint stress (CRS) model. • The impact of restraint stress on the LHb is not a static process but rather a dynamic one. • Spontaneous electrophysiological activity in LHb and its interaction with other potential targets can effectively distinguish the depressive state, which may provide sensitive biomarkers of depression. Closed-loop deep brain stimulation (DBS) system offers a promising approach for treatment-resistant depression, but identifying universally accepted electrophysiological biomarkers for closed-loop DBS systems targeting depression is challenging. There is growing evidence suggesting a strong association between the lateral habenula (LHb) and depression. Here, we took LHb as a key target, utilizing multi-site local field potentials (LFPs) to study the acute and chronic changes in electrophysiology, functional connectivity, and brain network characteristics during the formation of a chronic restraint stress (CRS) model. Furthermore, our model combining the electrophysiological changes of LHb and interactions between LHb and other potential targets of depression can effectively distinguish depressive states, offering a new way for developing effective closed-loop DBS strategies. [ABSTRACT FROM AUTHOR]

• The VP regulates activity of VTA DA neurons through direct and poly-synaptic effects. • The VP is critical for processing aversive stimuli and expressing adaptive behavior. • GABA, DA and endogenous opioids in the VP modulate responding to aversive stimuli. • Stimulation of GABAergic VP neurons supports reinforcement. • Stimulation of GABAergic VP neurons inhibits the LHb and activates VTA DA neurons. • Glutamatergic VP neurons promote avoidance. • Glutamatergic VP neurons are necessary for aversion-constraining of reward seeking. Responding to aversive and rewarding stimuli is essential to survival. The ventral pallidum (VP) is a critical node in the mesolimbic network, being the primary output of the nucleus accumbens and projecting to the lateral habenula (LHb) and ventral tegmental area (VTA). The VP is thus poised to modulate the habenula-tegmental circuitry and contribute to processing both rewarding and aversive stimuli. Here, we integrate human functional imaging, behavioral pharmacology in rodents, and recent optogenetic circuit dissection studies of the VP with a focus on the role of the neurochemically-distinct subpopulations in aversion processing. These recent results support a model in which glutamatergic VP neurons play a unique role in aversion processing, while canonical GABAergic VP neurons promote reinforcement and encode the hedonic value of reward. Genetic ablation of glutamatergic, but not GABAergic VP neurons abolishes devaluation of natural reward (sucrose) by pairing with an aversive stimulus (lithium chloride injection). Both of these populations modulate activity throughout the LHb and VTA, which is necessary for expression of adaptive behavior in response to rewarding or aversive stimuli. Future work will address how neuromodulators such as endogenous opioids or dopamine shape function and plasticity within these distinct populations of VP neurons, when these subpopulations are engaged during learning responses to rewarding and aversive stimuli, and how their activity is altered in models of reward-related disorders. Answering these questions will be necessary to understand the basis and ultimately develop targeted therapies for disorders of reward/aversion processing, such as affective, chronic pain and substance use disorders. [ABSTRACT FROM AUTHOR]

Highlights • Nesfatin-1 inhibits swallowing reflex. • Nesfatin-1 activates neurons located within the brainstem pattern generator of swallowing. • Oxytocin fibres adjoin brainstem nesfatin-1/NUCB2-expressing neurons. • Oxytocin inhibits swallowing reflex. • Blockade of oxytocin receptors prevents swallowing inhibition by nesfatin-1. Abstract Nesfatin-1, an 82-amino acid peptide encoded by the secreted precursor nucleobinin-2 (NUCB2), exerts potent anorexigenic action independently of leptin signaling. This propensity has propelled this peptide and its analogues as potential anti-obesity drug candidates. However, a more extensive comprehension of its biological actions is needed prior to envisaging its potential use in the treatment of metabolic diseases. Swallowing is an essential motor component of ingestive behavior, which induces the propulsion of the alimentary bolus from the mouth to the esophagus. The dorsal swallowing group (DSG) which constitutes a part of the central pattern generator of swallowing (SwCPG) is located within the solitary tract nucleus (STN), a region reported to contain nesfatin-1/NUCB2 expressing neurons. In this context, we investigate here the possible effects of nesfatin-1 on swallowing discharge. Nesfatin-1 dose-dependently inhibited swallowing reflex and activated neurons located in the DSG region. In addition, we provide evidences that strongly suggest that this nesfatin-1 inhibitory effect involved an oxytocinergic relay. Indeed, oxytocin (OT) injection at the brainstem level inhibited swallowing reflex and OT receptor antagonist prevented nesfatin-1 inhibitory action. Altogether, these data constitute the first demonstration that nesfatin-1 modulates swallowing reflex by acting at the brainstem level via an oxytocinergic relay. [ABSTRACT FROM AUTHOR]

[Display omitted] • Exercise decreases anxiety, aggressive behavior, and depression in mTBI mice. • Exercise normalizes altered synaptic plasticity and neurotransmitters levels in cortical and hippocampal regions of mTBI mice. Traumatic brain injuries (TBI) refer to multiple acquired dysfunctions arising from damage to the brain caused by an external force, including rapid acceleration/deceleration and concussion. Among them, mild TBI (mTBI) accounts for most cases (up to 90%) of injuries. It is responsible for a variety of symptoms, including anxiety, depression, and cognitive impairments that remain difficult to be treated. It has been reported that regular physical activity, as well as, improving life quality, display a neuroprotective function, suggesting a possible role in post-traumatic rehabilitation. In this study, we investigated the effects of treadmill exercise in a mice mTBI model by behavioural, electrophysiological and neurochemical analysis. Daily exercise decreased anxiety, aggressive behavior, and depression in mTBI mice. Accordingly, electrophysiological and neurochemical maladaptive rearrangement occurring in the hippocampus of mTBI mice were prevented by the exercise. [ABSTRACT FROM AUTHOR]

The S allele of serotonin transporter gene (5-HTTLPR) has been found to increase the risk of depression and other mental health problems, but some evidence suggests that S-allele carriers outperform subjects carrying the long allele in an array of cognitive tasks. Evidence linking this polymorphism with individual variation in electrophysiological properties of resting state brain networks is very limited. This study investigated the effect of 5-HTTLPR polymorphism on EEG current source density, connectivity, and topological properties of resting state networks. We collected genetic and resting state EEG data in 113 Caucasians. As compared to L-homozygotes, S-allele carriers showed lower current source density and connectivity in most frequency bands in areas overlapping with the default mode and emotion regulation regions. The analysis of graph-theoretical measures showed that S-allele carriers, as compared to L-homozygotes, have less optimal topological properties of brain networks in theta, but more optimal in alpha band. This dissociation may reflect the predisposition to emotional disorders, which is inherent to S-allele carriers, and, on the other hand, their superior functioning in some cognitive domains. [ABSTRACT FROM AUTHOR]

In contrast to the large number of studies investigating the electrophysiological properties and synaptic connectivity of hippocampal pyramidal neurons, granule cells, and GABAergic interneurons, much less is known about Cajal-Retzius cells. In this review article, we discuss the possible reasons underlying this difference, and review experimental work performed on this cell type in the hippocampus, comparing it with results obtained in the neocortex. Our main emphasis is on data obtained with in vitro electrophysiology. In particular, we address the bidirectional connectivity between Cajal-Retzius cells and GABAergic interneurons, examine their synaptic properties and propose specific functions of Cajal-Retzius cell/GABAergic interneuron microcircuits. Lastly, we discuss the potential involvement of these microcircuits in critical physiological hippocampal functions such as postnatal neurogenesis or pathological scenarios such as temporal lobe epilepsy. [ABSTRACT FROM AUTHOR]

Dural afferent neurons are implicated in primary headaches including migraine. Although a significant portion of primary afferent neurons innervating the dura are myelinated A-type neurons, previous electrophysiological studies have primarily characterized the functional properties of small-sized C-type sensory neurons. Here we show the functional characterization of dural afferent neurons identified with the fluorescent dye DiI. DiI-positive neurons were divided into three types: small-, medium-, and large-sized neurons, based on their diameter, area, and membrane capacitance. The immunoreactivity of NF200, a marker of A-type myelinated neurons, was detected in most large-sized, but it was also present in a limited number of small- and medium-sized DiI-positive neurons. Capsaicin, a transient receptor potential vanilloid 1 agonist, induced the membrane currents in most small- and medium-sized neurons, but not in large-sized DiI-positive neurons. Tetrodotoxin-resistant Na + channels were expressed in almost all types of DiI-positive neurons. Mechanosensitive currents were detected from a majority of large-sized, and to a lesser extent, small- and medium-sized DiI-positive neurons. The results suggest that most dural afferent neurons are nociceptive, e.g., polymodal C-type for small- and medium-sized neurons, and high-threshold nociceptive A-type mechanoreceptors for large-sized neurons. We also found that DiI-positive neurons differed with respect to passive and active membrane properties, and that sumatriptan, a representative drug used for the acute treatment of migraine attack, inhibited voltage-gated Ca 2+ currents in all types of DiI-positive neurons. The present results showing the nociceptive properties of dural afferent neurons would contribute to understand the pathophysiology of primary headaches. [ABSTRACT FROM AUTHOR]

The success of neuromodulation therapies, particularly in the brain, spinal cord, and peripheral nerves, has been greatly aided by computational, biophysical models. However, treating gastrointestinal disorders with electrical stimulation has been much less explored, partly because the mode of action of such treatments is unclear, and selection of stimulation parameters is often empirical. Progress in gut neuromodulation is limited by the comparative lack of biophysical models capable of simulating neuromodulation of gastrointestinal function. Here, we review the recently developed biophysical models of electrically-active cells in the gastrointestinal system that contribute to motility. Biophysical models are replacing phenomenologically-defined models due to advancements in electrophysiological characterization of key players in the gut: enteric neurons, smooth muscle fibers, and interstitial cells of Cajal. In this review, we explore existing biophysically-defined cellular and network models that contribute to gastrointestinal motility. We focus on recent models that are laying the groundwork for modeling electrical stimulation of the gastrointestinal system. Developing models of gut neuromodulation will improve our mechanistic understanding of these treatments, leading to better parameterization, selectivity, and efficacy of neuromodulation to treat gastrointestinal disorders. Such models may have direct clinical translation to current neuromodulation therapies, such as sacral nerve stimulation. [ABSTRACT FROM AUTHOR]

Gastric peristalsis is initiated and coordinated by an underlying bioelectrical activity, termed slow waves. High-resolution (HR) mapping of the slow waves has become a fundamental tool for accurately defining electrophysiological properties in gastroenterology, including dysrhythmias in gastric disorders such as gastroparesis and functional dyspepsia. Currently, HR mapping is achieved via acquisition of slow waves taken directly from the serosa of fasted subjects undergoing invasive abdominal surgery. Recently, a minimally invasive retractable catheter and electrode has been developed for HR mapping that can only be used in short-term studies in subjects undergoing laparoscopy. Noninvasive mapping has also emerged from multichannel cutaneous electrogastrography; however, it lacks sufficient resolution and is prone to artifacts. Bioelectronics that can map slow waves in conscious subjects, postprandially and long-term, are in high demand. Due to the low signal-to-noise ratio of cutaneous electrogastrography, electrodes for HR mapping of gut activity have to acquire slow waves directly from the gut; hence, development of novel device implantation methods has inevitably accompanied development of the devices themselves. Initial efforts that have paved the way toward achieving these goals have included development of miniature wireless systems with a limited number of acquisition channels using commercially available off-the-shelf electronic components, flexible HR electrodes, and endoscopic methods for minimally invasive device implantation. To further increase the spatial resolution of HR mapping, and to minimize the size and power consumption of the implant for long-term studies, application-specific integrated circuitry, wireless power transfer, and stretchable electronics technologies have had to be integrated into a single system. [ABSTRACT FROM AUTHOR]

Languages around the world use spatial terminology, like prepositions, to describe non-spatial, abstract concepts, including time (e.g., in the moment ). The Metaphoric Mapping Theory explains this pattern by positing that a universal human cognitive process underlies it, whereby abstract concepts are conceptualized via the application of concrete, three-dimensional space onto abstract domains. The alternative view is that the use of spatial propositions in abstract phrases is idiomatic, and thus does not trigger metaphoric mapping. In the current study, event-related potentials (ERPs) were used to examine the time-course of neural processing of concrete and abstract phrases consisting of the prepositions in or on followed by congruent and incongruent nouns (e.g., in the bowl/plate and in the moment/mend ). ERPs were recorded from the onset of reference nouns in 28 adult participants using a 128-channel electrode net. Results show that congruency has differential effects on neural measures, depending on whether the noun is concrete or abstract. Incongruent reference nouns in concrete phrases (e.g., on the bowl ) elicited a significant central negativity (an N400 effect), while incongruent reference nouns in abstract phrases (e.g., on the moment ) did not. These results suggest that spatially incongruent concrete nouns are semantically unexpected (N400 effect). A P600 effect, which might indicate rechecking, reanalysis and/or reconstruction, was predicted for incongruent abstract nouns, but was not observed, possibly due to the variability in abstract stimuli. Findings cast doubt on accounts claiming that abstract uses of prepositions are cognitively and metaphorically linked to their spatial sense during natural, on-line processing. [ABSTRACT FROM AUTHOR]

To evaluate the role of afferent information from the salivary gland, we analyzed the neural activity of the sensory nerve innervating the submandibular gland in anesthetized rats. The sensory nerves running through the parasympathetic nerve supply responded to mechanical pressure applied to the surface of the main duct and the body of the gland, whilst those in the sympathetic nerve supply responded only to the body of the gland. The sensory nerves in the sympathetic and parasympathetic nerve routes responded to pressure in the duct system produced by a retrograde injection of saline into the main duct. The threshold pressure for production of afferent discharges was higher than the maximum secretory pressure evoked by electrical stimulation of the parasympathetic secretory nerve. The retrograde ductal injection of drugs related to the inflammatory process (capsaicin and bradykinin) evoked intense multi-unit discharges in the sensory nerves of both routes. The sensory nerve in the sympathetic route was responsive to ligation of the artery to the gland. These results suggest that sensory nerves in the sympathetic and parasympathetic routes mainly conduct noxious information, and that those in the sympathetic route are responsive to ischemia and may control blood flow of the gland. [ABSTRACT FROM AUTHOR]

Various neurological and psychiatric diseases lead to alterations in cortical serotonergic activity as one of their underlying processes. However, the electrophysiological implication of changes in serotonergic activity remains a matter of investigation. In this study, we investigated whether brain serotonergic activity influences the excitability-related phenomenon known as cortical spreading depression (CSD). CSD parameters (propagation velocity, and amplitude and duration of the DC-shift) was evaluated in rats that received two treatments that increased cortical serotonergic activity, electrical stimulation of the raphe nuclei and subcutaneous injection of a selective serotonin reuptake inhibitor, sumatriptan. A third group of rats was tested on a low-tryptophan diet rat model of serotonin depletion. Control rats for these three groups received, respectively, sham raphe stimulation, saline injection, and a tryptophan-supplemented diet. Compared to controls, electrical stimulation of the raphe nuclei and sumatriptan administration decelerated CSD and increased the duration of the negative DC-shift of CSD, whereas the low-tryptophan diet was associated with significantly accelerated CSD propagation and shortened DC-shift of CSD (p < 0.05). We concluded that serotonergic neurons are very important for stabilizing the delicate equilibrium between excitatory and inhibitory neuronal influences that determines cortical excitability and CSD propagation. Our pharmacological, electrophysiological and dietary data suggest that cortical serotonergic activity negatively modulates CSD propagation in the rat cortex. Reduced central serotonergic activity, as can be observed in several neurological and psychiatric diseases, may constitute a pathological factor for increased sensitivity to CSD. [ABSTRACT FROM AUTHOR]

A polyglycolic acid-collagen (PGA-c) tube was used as an artificial nerve guide during facial nerve reconstruction performed in a canine model of stellate ganglion block (SGB). The model was generated using a cervical sympathetic ganglionectomy. We evaluated the effects of blood flow on nerve regeneration. First, we resected the left cervical sympathetic ganglion in beagles (n = 6). We assessed buccal mucosal blood flow and nasal skin temperatures once per week for 12 weeks and Horner’s sign 2, 4, and 6 months after resection. We compared these values to those measured prior to resection. Blood flow was increased for 6–11 weeks, but sympathetic control remained blocked after 6 months. Second, we divided beagles into 3 groups: resection models (negative control), from which 7 mm of the left facial nerve buccal branch was resected (n = 5); reconstruction models, which underwent nerve reconstruction using PGA-c tubes (n = 6); and SGB + reconstruction models, which underwent a left cervical sympathetic ganglionectomy immediately after reconstruction (n = 6). The right side of the face served as control (n = 17). Nerve regeneration was significantly greater in the SGB + reconstruction model dogs than in the reconstruction model dogs, as measured by both electrophysiological and morphological analyses at postoperative week 12. In particular, motor nerve conduction velocity was increased approximately 2-fold (p = 0.018). We were able to generate an SGB model with long-term increased blood flow facilitated by the promotion of facial nerve regeneration by PGA-c tubes. [ABSTRACT FROM AUTHOR]

TREK-2-like channels were identified on the basis of electrophysiological and pharmacological tests performed on freshly isolated and enzymatically/mechanically dispersed pyramidal neurons of the rat medial prefrontal cortex (mPFC). Single-channel currents were recorded in cell-attached configuration and the impact of adrenergic receptors (α 1 , α 2 , β) stimulation on spontaneously appearing TREK-2-like channel activity was tested. The obtained results indicate that noradrenaline decreases the mean open probability of TREK-2-like channel currents by activation of β 1 but not of α 1 - and α 2 -adrenergic receptors. Mean open time and channel conductance were not affected. The system of intracellular signaling pathways depends on the activation of protein kinase A. We also show that adrenergic control of TREK-2-like channel currents by adrenergic receptors was similar in pyramidal neurons isolated from young, adolescent, and adult rats. Immunofluorescent confocal scans of mPFC slices confirmed the presence of the TREK-2 protein, which was abundant in layer V pyramidal neurons. The role of TREK-2-like channel control by adrenergic receptors is discussed. [ABSTRACT FROM AUTHOR]

Studies of the antidepressant vortioxetine have demonstrated beneficial effects on cognitive dysfunction associated with depression. To elucidate how vortioxetine modulates neuronal activity during cognitive processing we investigated the effects of vortioxetine (3 and 10 mg/kg) in rats performing an auditory oddball (deviant target) task. We investigated neuronal activity in target vs non-target tone responses in vehicle-treated animals using electroencephalographic (EEG) recordings. Furthermore, we characterized task performance and EEG changes in target tone responses of vortioxetine vs controls. Quantification of event-related potentials (ERPs) was supplemented by analyses of spectral power and inter-trial phase-locking. The assessed brain regions included prelimbic cortex, the hippocampus, and thalamus. As compared to correct rejection of non-target tones, correct target tone responses elicited increased EEG power in all regions. Additionally, neuronal synchronization was increased in vehicle-treated rats during both early and late ERP responses to target tones. This indicates a significant consistency of local phases across trials during high attentional load. During early sensory processing, vortioxetine increased both thalamic and frontal synchronized gamma band activity and EEG power in all brain regions measured. Finally, vortioxetine increased the amplitude of late hippocampal P3-like ERPs, the rodent correlate of the human P300 ERP. These findings suggest differential effects of vortioxetine during early sensory registration and late endogenous processing of auditory discrimination. Strengthened P3-like ERP response may relate to the pro-cognitive profile of vortioxetine in rodents. Further investigations are warranted to explore the mechanism by which vortioxetine increases network synchronization during attentive and cognitive processing. [ABSTRACT FROM AUTHOR]

A rare omission of a sound that is predictable by anticipatory visual information induces an early negative omission response (oN1) in the EEG during the period of silence where the sound was expected. It was previously suggested that the oN1 was primarily driven by the identity of the anticipated sound. Here, we examined the role of temporal prediction in conjunction with identity prediction of the anticipated sound in the evocation of the auditory oN1. With incongruent audiovisual stimuli (a video of a handclap that is consistently combined with the sound of a car horn) we demonstrate in Experiment 1 that a natural match in identity between the visual and auditory stimulus is not required for inducing the oN1, and that the perceptual system can adapt predictions to unnatural stimulus events. In Experiment 2 we varied either the auditory onset (relative to the visual onset) or the identity of the sound across trials in order to hamper temporal and identity predictions. Relative to the natural stimulus with correct auditory timing and matching audiovisual identity, the oN1 was abolished when either the timing or the identity of the sound could not be predicted reliably from the video. Our study demonstrates the flexibility of the perceptual system in predictive processing (Experiment 1) and also shows that precise predictions of timing and content are both essential elements for inducing an oN1 (Experiment 2). [ABSTRACT FROM AUTHOR]

This study explored interpersonal influences on electrophysiological responses during the anticipation of tactile stimulation. It is well-known that broad, negative-going potentials are present in the event-related potential (ERP) between a forewarning cue and a tactile stimulus. It has also been shown that the alpha-range mu rhythm shows a lateralized desynchronization over central electrode sites during anticipation of tactile stimulation of the hand. The current study used a tactile discrimination task in which a visual cue signaled that an upcoming stimulus would either be delivered 1500 ms later to the participant’s hand, to a task partner’s hand, or to neither person. For the condition in which participants anticipated the tactile stimulation to their own hand, a negative potential (contingent negative variation, CNV) was observed in the ERP at central sites in the 1000 ms prior to the tactile stimulus. Significant mu rhythm desynchronization was also present in the same time window. The magnitudes of the ERPs and of the mu desynchronization were greater in the contralateral than in the ipsilateral hemisphere prior to right hand stimulation. Similar ERP and EEG changes were not present when the visual cue indicated that stimulation would be delivered to the task partner or to neither person. The absence of social influences during anticipation of tactile stimulation, and the relationship between the two brain signatures of anticipatory attention (CNV and mu rhythm) are discussed. [ABSTRACT FROM AUTHOR]

The dentate gyrus (DG) as part of the hippocampal formation is believed to serve as a gatekeeper with strong inhibitory properties against uncontrolled propagation of neuronal activity from the entorhinal cortex and neocortical structures. In temporal lobe epilepsy, the DG becomes hyperexcitable and loses its gate function, enabling propagation of ictal activity into downstream structures such as CA3 and CA1 areas. Furthermore, the DG, apart from facilitating propagation, may also be able to autonomously generate ictal activity, but this point has remained open so far. To tackle this question, we used intrinsic optical imaging in combination with electrophysiological recordings in brain slice preparations from rats in which status epilepticus had been induced electrically several weeks prior to measurements. Upon omission of Mg ++ from the artificial cerebrospinal fluid, in 15 out of 33 slices (45.4%) from 9 out of 13 epileptic animals (69.2%), spontaneous and autonomous ictal activity, mostly seizure-like events (SLE), was observed in the DG. This activity manifested independently from SLE generated in adjacent cortices and never occurred in slices from control animals. SLE generated in the DG differed from those with origin in the entorhinal or temporal cortex by longer latency to the first event after Mg ++ omission (p < 0.001), a higher SLE frequency (p < 0.05), higher amplitude (p < 0.001) and a longer SLE duration (p < 0.05). We conclude that in epilepsy, the DG, in addition to facilitated gating of activity from upstream structures, can serve as an independent generator of ictal activity. [ABSTRACT FROM AUTHOR]

Numerous studies have shown that certain types of striatal interneurons play a crucial role in selection and regulation of striatal output. Striatal Fast-Spiking Interneurons (FSIs) are parvalbumin positive, GABAergic interneurons that constitute less than 1% of the total striatal population. It is becoming increasingly evident that these sparsely distributed neurons exert a strong inhibitory effect on Medium Spiny projection Neurons (MSNs). MSNs in lateral striatum receive direct synaptic input from regions of cortex representing discrete body parts, and show phasic increases in activity during touch or movement of specific body parts. In the present study, we sought to determine whether lateral striatal FSIs identified by their electrophysiological properties, i.e., short-duration spike and fast firing rate (FR), display body part sensitivity similar to that exhibited by MSNs. During video recorded somatosensorimotor exams, each individual body part was stimulated and responses of single neurons were observed and quantified. Individual FSIs displayed patterns of activity related selectively to stimulation of a discrete body part. Most patterns of activity were similar to those exhibited by typical MSNs, but some phasic decreases were observed. These results serve as evidence that some striatal FSIs process information related to discrete body parts and participate in sensorimotor processing by striatal networks that contribute to motor output. Statement of Significance Parvalbumin positive, striatal FSIs are hypothesized to play an important role in behavior by inhibiting MSNs. We asked a fundamental question regarding information processed during behavior by FSIs: whether FSIs, which preferentially occupy the sensorimotor portion of the striatum, process activity of discrete body parts. Our finding that they do, in a selective manner similar to MSNs, begins to reveal the types of phasic signals that FSI feed forward to projection neurons during striatal processing of cortical input regarding a specific sensorimotor event. These findings suggest new avenues for testing feed-forward inhibition theory as applied to striatum in naturalistic conditions, such as whether FSI decreases facilitate excitation of MSNs related to the current movement while FSI increases silence MSNs unrelated to the current movement. [ABSTRACT FROM AUTHOR]

Partial agonists have lower efficacies than compounds considered ‘full agonists’, eliciting submaximal responses even at saturating concentrations. Taurine is a partial agonist at the glycine receptor (GlyR), a member of the cys-loop ligand-gated ion channel superfamily. The molecular mechanisms responsible for agonism are not fully understood but evidence suggests that efficacy at these receptors is determined by conformational changes that occur early in the process of receptor activation. We previously identified a residue located near the human α1 glycine binding site (aspartate-97; D97) that, when mutated to arginine (D97R), results in GlyR channels opening spontaneously with a high open probability, mimicking the effects of saturating glycine concentrations on wildtype GlyR. This D97 residue is hypothesized to form an electrostatic interaction with arginine-119 on an adjacent subunit, stabilizing the channel in a shut state. Here we demonstrate that the disruption of this putative bond increases the efficacy of partial agonists including taurine, as well as two other β-amino acid partial agonists, β-aminobutyric acid (β-ABA) and β-aminoisobutyric acid (β-AIBA). Even the subtle charge-conserving mutation of D97 to glutamate (D97E) markedly affects partial agonist efficacy. Mutation to the neutral alanine residue in the D97A mutant mimics the effects seen with D97R, indicating that charge repulsion does not significantly affect these findings. Our findings suggest that the determination of efficacy following ligand binding to the glycine receptor may involve the disruption of an intersubunit electrostatic interaction occurring near the agonist binding site. [ABSTRACT FROM AUTHOR]

A controversy in emotion research concerns the question of whether affective or cognitive primacy are evident in processing affective stimuli and the factors contributing to each alternative. Using electrophysiological recordings in an adapted visual oddball paradigm allowed tracking the dynamics of affective and cognitive effects. Stimuli consisted of face pictures displaying affective expressions with rare oddballs differing from frequent stimuli in either affective expression, structure (while frequent stimuli were shown frontally these deviants were turned sideways) or they differed on both dimensions, i.e. in affective expression and structure. Results revealed a defined sequence of differences in ERP amplitudes: For stimuli deviating in their affective expression only, P1 modulations ~100 ms were evident, while affective differences of structure deviants were not evident before the N170 time window. All three types of deviants differed in P300 amplitudes, indicating integration of affective and structural information. These results encompass evidence for both, cognitive and affective primacy depending on stimulus properties. Specifically affective primacy is only visible when the respective facial features can be extracted with ease. When structural differences make face processing harder, however, cognitive primacy is brought forward. [ABSTRACT FROM AUTHOR]

Neural circuit formation is a critical process in brain development. Axon guidance molecules, their receptors, and intracellular mediators are important to establish neural circuits. Collapsin response mediator proteins (CRMPs) are known intercellular mediators of a number of repulsive guidance molecules. Studies of mutant mice suggest roles of CRMPs in dendrite development. However, molecular mechanisms of CRMP-mediated dendritic development remain to elucidate. In this study, we show abnormal orientation of basal dendrites (extension to deeper side) of layer V pyramidal neurons in the cerebral cortex of CRMP4−/− mice. Moreover, we observed severe abnormality in orientation of the basal dendrites of these neurons in double knockout of CRMP1 and 4, suggesting redundant functions of these two genes. Redundant gene functions were also observed in proximal bifurcation phenotype in apical dendrites of hippocampal CA1 pyramidal neurons. These results indicate that CRMP1 and CRMP4 regulate proper orientation of the basal dendrites of layer V neurons in the cerebral cortex. [ABSTRACT FROM AUTHOR]

The ability to recognize faces of family members, friends, and acquaintances plays an important role in our daily interactions. The other-race effect is the reduced ability to recognize other-race faces as compared to own-race faces. Previous studies showed different patterns of event-related potentials (ERPs) associated with recollection and familiarity during memory encoding (i.e., Dm) and recognition (i.e., parietal old/new effect) for own-race and other-race faces in a subjective-recollection task (remember-know judgments). The present study investigated the same neural correlates of the other-race effect in an associative-memory task, in which Caucasian and East Asian participants learned and recognized own-race and other-race faces along with background colors. Participants made more false alarms for other-race faces indicating lower memory performance. During the study phase, subsequently recognized other-race faces (with and without correct background information) elicited more positive mean amplitudes than own-race faces, suggesting increased neural activation during encoding of other-race faces. During the test phase, recollection-related old/new effects dissociated between own-race and other-race faces. Old/new effects were significant only for own-race but not for other-race faces, indicating that recognition only of own-race faces was supported by recollection and led to more detailed memory retrieval. Most of these results replicated previous studies that used a subjective-recollection task. Our study also showed that the increased demand on memory encoding during an associative-memory task led to Dm patterns that indicated similarly deep memory encoding for own-race and other-race faces. [ABSTRACT FROM AUTHOR]

Temporal context, memory for the timing of events, can be assessed using non-temporal strategies such as relative familiarity or inference from a semantic narrative. Neuroimaging studies, which have previously encouraged such strategies, find similar patterns of brain regions involved in both temporal and non-temporal context memory. The present study aims to investigate whether previous findings are driven by the use of non-temporal strategies or whether the same pattern of brain regions is identified when relative familiarity and semantic narrative strategies are discouraged. We used abstract phrases (e.g. alone me leave) created by scrambling familiar three-word phrases. The words in the phrases were less concrete than the object image stimuli used in previous studies of temporal context memory (Jenkins and Ranganath, 2010) and were presented quickly while participants read each word aloud. This differed from previous studies in which participants were encouraged to use narrative strategies during encoding (Tubridy and Davachi, 2011) and was designed to discourage use of narrative strategies. The relative familiarity of the words within each phrase was similar and likely not diagnostic of word order during encoding, in order to minimize the use of relative familiarity strategies. Neuroimaging results indicate that temporal context retrieval was associated with the hippocampus, parahippocampal cortex, ventromedial prefrontal cortex, and retrosplenial cortex, which are regions consistent with the retrieval of non-temporal context in episodic memory, suggesting that previous findings were not driven entirely by non-temporal strategies but rather that temporal memory relies on similar brain regions to non-temporal memory. [ABSTRACT FROM AUTHOR]

• This event-related potential study is an investigation of the processing of Mandarin short passives. We used a syntactic violation paradigm to compare the processing of two auxiliary phrases (i.e., a verb-modifier di -phrase and a noun-modifier de -phrase). • ERP data showed that noun-modifier elicited a greater left anterior negativity (LAN) and P600 effect than the verb-modifier, in both the control condition and the violation condition. • We also observed that the LAN induced by the verb-modifier phrase was greater in the control condition than that in the violation condition, while the LAN induced by the noun-modifier was greater in the violation condition than that in the control condition. • The greater cortical LAN-P600 might differentiate the high-level hierarchy from the low-level hierarchy. • We tentatively hold that a constructional alternation might be activated during the processing of the target structure (i.e., long passives might be the default representational mode of short passives). This event-related potentials study explored the processing of Mandarin short passives. We used a syntactic violation paradigm to compare the processing of two auxiliary phrases (i.e., a verb-modifier di -phrase and a noun-modifier de -phrase). In the control condition, the syntactic hierarchy of the di -phrase was lower than that of the de -phrase. In the violation condition, the low-level violation was created by replacing di with de in the auxiliary phrase, while the high-level violation was created by replacing de with di in the auxiliary phrase. The ERP data showed that the noun-modifier elicited the greater left anterior negativity (LAN) and the P600 than the verb-modifier, in both the control condition and the violation condition. We also observed that the LAN induced by the verb-modifier phrase was greater in the control condition than that in the violation condition, while the LAN induced by the noun-modifier was greater in the violation condition than that in the control condition. These results suggested that the greater cortical LAN-P600 might differentiate the high-level hierarchy from the low-level hierarchy. In addition, we tentatively claimed that given the same predicate argument structure, long passives might be the default representational mode of short passives (generally, a constructional alternation might be activated during the processing of the target structure). [ABSTRACT FROM AUTHOR]

[Display omitted] • BDNF via its receptor TrkB enhances the excitability and decreases the membrane input resistance and membrane time constant of song premotor nucleus RA projection neurons in adult male zebra finches. • BDNF via TrkB increases the excitatory synaptic transmission of RA projection neurons through presynaptic mechanisms. • These findings suggest a possible cellular mechanism of BDNF regulating song behavior of songbirds. The singing of songbirds is a complex vocal behavior. It was reported that brain-derived neurotrophic factor (BDNF), a key neurotrophic factor involved in neuronal survival and activity, plays an important role in regulation of songbirds' song behavior. In all song-related nuclei, the electrophysiological activity of robust nucleus of the arcopallium (RA) in the forebrain of songbirds is directly related to birdsong output. Whether BDNF regulates the electrophysiological activity and synaptic transmission of RA causing the change of song behavior need be further explored. In this study, the effects of BDNF on the electrophysiological activity and excitatory synaptic transmission of RA projection neurons (PNs) in adult male zebra finches were investigated using whole-cell patch clamp recordings in vitro. Our results showed that BDNF increased the firing of evoked action potentials in RA PNs and decreased the membrane input resistance and membrane time constant of RA PNs, indicating that BDNF can promote RA PNs excitability by reducing membrane input resistance and membrane time constant. Meanwhile, BDNF increased the frequency rather than amplitude of miniature excitatory postsynaptic currents (mEPSCs) in RA PNs. Moreover, the effects of BDNF on the excitability, intrinsic membrane properties and mEPSCs of RA PNs were blocked by its receptor TrkB antagonist K252a. These results indicate that BDNF via TrkB enhances the excitability and excitatory synaptic transmission of RA PNs in adult male songbirds through presynaptic mechanisms, suggesting a possible cellular mechanism by which BDNF regulates song behavior. [ABSTRACT FROM AUTHOR]

The canonical Wnt signaling pathway plays an important role in embryogenesis, and the establishment of neurogenic niches. It is involved in proliferation and differentiation of neural progenitors, since elevated Wnt/β-catenin signaling promotes differentiation of neural stem/progenitor cells (NS/PCs 1 1 NS/PCs, neural stem/progenitor cells. ) towards neuroblasts. Nevertheless, it remains elusive how the differentiation program of neural progenitors is influenced by the Wnt signaling output. Using transgenic mouse models, we found that in vitro activation of Wnt signaling resulted in higher expression of β-catenin protein and Wnt/β-catenin target genes, while Wnt signaling inhibition resulted in the reverse effect. Within differentiated cells, we identified three electrophysiologically and immunocytochemically distinct cell types, whose incidence was markedly affected by the Wnt signaling output. Activation of the pathway suppressed gliogenesis, and promoted differentiation of NS/PCs towards a neuronal phenotype, while its inhibition led to suppressed neurogenesis and increased counts of cells of glial phenotype. Moreover, Wnt signaling hyperactivation resulted in an increased incidence of cells expressing outwardly rectifying K + currents, together with inwardly rectifying Na + currents, a typical current pattern of immature neurons, while blocking the pathway led to the opposite effect. Taken together, our data indicate that the Wnt signaling pathway orchestrates neonatal NS/PCs differentiation towards cells with neuronal characteristics, which might be important for nervous tissue regeneration during central nervous system disorders. Furthermore, the transgenic mouse strains used in this study may serve as a convenient tool to manipulate β-catenin-dependent signaling in neural progenitors in the neonatal brain. [ABSTRACT FROM AUTHOR]

Ventilation is peripherally controlled by afferent activity arising from the peripheral chemoreceptors. In the rat, chemosensory activity is conveyed to the central nervous system through axons of neurons located in the nodose-petrosal-jugular-complex. These neurons have distinct electrophysiological properties, including a persistent Na + current. Acute blockade of this current with phenytoin and other anti-epileptic drugs reduces normoxic chemosensory activity and responses to acute hypoxia. However, because anti-epileptic therapy is prolonged and there is no information on the effects of chronic phenytoin treatment on peripheral chemosensory activity, we studied the effects of long-lasting phenytoin treatment (~25 days) on afferent chemosensory activity, on a wide range of oxygen inspiratory fractions. Osmotic pumps containing dissolved phenytoin (166 mg/mL) or vehicle (daily flow: 60 µL) were implanted subcutaneously in male adult Sprague Dawley rats. At the end of the treatment, the animals were anesthetized and carotid sinus nerve activity was recorded in vivo. Afferent chemosensory activity in normoxia was not significantly different between control (71.2±2.2 Hz) and phenytoin treated (95.4±2.1 Hz) rats. In contrast, carotid body chemosensory responses to acute hypoxic challenges were markedly reduced in phenytoin treated rats, specifically in the lowest part of the hypoxic range (control 133.5±18.0 Hz vs phenytoin treated 50.2±29.4, at 5% F I O 2 ). Chronic phenytoin treatment severely impaired the chemosensory responses to acute hypoxia, suggesting that long-term phenytoin treatment in patients may result in a reduced peripheral respiratory drive together with a reduction in the respiratory responses to hypoxic challenges. [ABSTRACT FROM AUTHOR]

Pelvic nerve (PN) bladder primary afferent neurons were retrogradely labeled by intraparenchymal (IPar) microinjection of fluorescent tracer or intravesical (IVes) infusion of tracer into the bladder lumen. IPar and IVes techniques labeled two distinct populations of PN bladder neurons differentiated on the basis of dorsal root ganglion (DRG) soma labeling, dye distribution within the bladder, and intrinsic electrophysiological properties. IPar (Fast blue)- and IVes (DiI)-labeled neurons accounted for 91.5% (378.3±32.3) and 8% (33.0±26.0) of all labeled neurons, respectively (p<0.01), with only 2.0±1.2 neurons labeled by both techniques. When dyes were switched, IPar (DiI)- and IVes (Fast blue) labeled neurons accounted for 77.6% (103.0±25.8) and 22.4% (29.8±10.5), respectively (P<0.05), with 6.0±1.5 double-labeled neurons. Following IPar labeling, DiI was distributed throughout non-urothelial layers of the bladder. In contrast, dye was contained within the urothelium and occasionally the submucosa after IVes labeling. Electrophysiological properties of DiI-labeled IPar and IVes DRG neurons were characterized by whole-mount, in situ patch-clamp recordings. IPar- and IVes-labeled neurons differed significantly with respect to rheobase, input resistance, membrane capacitance, amplitude of inactivating and sustained K + currents, and rebound action potential firing, suggesting that the IVes population is more excitable. This study is the first to demonstrate that IVes labeling is a minimally invasive approach for retrograde labeling of PN bladder afferent neurons, to selectively identify urothelial versus non-urothelial bladder DRG neurons, and to elucidate electrophysiological properties of urothelial and non-urothelial afferents in an intact DRG soma preparation. [ABSTRACT FROM AUTHOR]

Typically, in task-switching contexts individuals are slower and less accurate when repeating a task in mixed blocks compared to single-task blocks (mixing cost) and when switching to a new task compared to repeating a previous one (switch cost). Previous research has shown that distinct electrophysiological correlates underlie these two phenomena. However, this evidence is not a consistent result. The goal of this study was to better characterize differences between the control processes involved in mixing and switch costs. To this aim, we examined event-related potentials (ERPs) evoked during a cued task-switching experiment. In order to minimize the confounding effects of cognitive demands unrelated to task-switching, we asked participants to shift between two simple tasks (a letter identity task and a letter position task). The mixing cost was defined, in terms of ERPs, by contrasting repeat and single-task trials, whereas the ERP switch cost was obtained from the comparison of switch and repeat trials. Cue-locked ERPs showed that the mixing cost was mediated by two sustained components, an early posterior positivity and a late anterior negativity. On the other hand, the switch cost was associated with two early phasic positive components, one principally distributed over centro-parietal sites and the other located over left posterior sites. In target-locked ERPs the mixing cost was expressed by a frontal positivity, whereas the switch cost was expressed by a reduced parietal P3b. Overall, the results extend previous findings by providing elucidating ERP evidence on distinct proactive and reactive control processes involved in mixing and switch costs. [ABSTRACT FROM AUTHOR]

fMRI studies have implicated the medial prefrontal cortex and medial temporal lobe, components of the default mode network (DMN), in episodic prospection. This study compared quantitative EEG localized to these DMN regions during prospection and during resting and while waiting for rewards. EEG was recorded in twenty-two adults while they were asked to (i) envision future monetary episodes; (ii) wait for rewards and (iii) rest. Activation sources were localized to core DMN regions. EEG power and phase coherence were compared across conditions. Prospection, compared to resting and waiting, was associated with reduced power in the medial prefrontal gyrus and increased power in the bilateral medial temporal gyrus across frequency bands as well as greater phase synchrony between these regions in the delta band. The current quantitative EEG analysis confirms prior fMRI research suggesting that medial prefrontal and medial temporal gyrus interactions are central to the capacity for episodic prospection. [ABSTRACT FROM AUTHOR]

Introduction Prenatal stress (PNS) and stress in adulthood are risk factors for development of major depressive disorder. The present study aimed to 1) confirm previous neuroendocrine and behavioral changes induced by PNS, and 2) to characterize the effect of early- and late life stress on the in vivo activity of monoamine systems. Methods Gestational dams were restrained thrice daily under bright illumination from gestational day (GD)11–20. Behavior and neuroendocrine responses to the forced swim test (FST) were determined in adult (50–80 days) offspring, and electrophysiological single unit recordings of dorsal raphe nucleus serotonin (5-HT), ventral tegmental area dopamine (DA) and locus coeruleus norepinephrine (NE) neurons were obtained at baseline and 24 h after the FST. Results Gestational dams did not habituate to chronic restraint stress, and PNS reduced the birth weight of offspring. In adulthood, swim stress elevated CORT levels longer in PNS animals, while it had no effect on swim behaviors. Baseline firing activity of 5-HT neurons was decreased in PNS animals, while the firing activity of NE and DA neurons was increased. Swim stress had no effect on the firing on 5-HT neurons, but normalized the firing activity of catecholamine neurons in PNS animals. Conclusion The present data confirm previously established effects on neuroendocrine and physiological measures, and demonstrate an altering effect of PNS and stress on monoamine system activities in adulthood. Since PNS did not result in a depressive-like phenotype, these central changes following PNS might play reflect adaptive changes contributing to stress resilience in adulthood. [ABSTRACT FROM AUTHOR]

The atypical antipsychotic clozapine is widely used for treatment-resistant schizophrenic patients. Clozapine and its major active metabolite, N -desmethylclozapine (NDMC), have complex pharmacological properties, and interact with various neurotransmitter receptors. There are several biochemical studies reporting that NDMC exhibits a partial agonist profile at the human recombinant M 1 muscarinic receptors. However, direct electrophysiological evidence showing the ability of NDMC to activate native M 1 receptors in intact neurons is poor. Using rat hippocampal neurons, we previously demonstrated that activation of muscarinic receptors by a muscarinic agonist, oxotremorine M (oxo-M), induces a decrease in outward K + current at −40 mV. In the present study, using this muscarinic current response we assessed agonist and antagonist activities of clozapine and NDMC at native muscarinic receptors in intact hippocampal excitatory and inhibitory neurons. Suppression of the oxo-M-induced current response by the M 1 antagonist pirenzepine was evident only in excitatory neurons, while the M 3 antagonist darifenacin was effective in both types of neurons. Muscarinic agonist activity of NDMC was higher than that of clozapine, higher in excitatory neurons than in inhibitory neurons, sensitive to pirenzepine, and partially masked when co-applied with clozapine. Muscarinic antagonist activity of clozapine as well as NDMC was not different between excitatory and inhibitory neurons, but clozapine was more effective than NDMC. These results demonstrate that NDMC has the ability to activate native M 1 receptors expressed in hippocampal excitatory neurons, but its agonist activity might be limited in clozapine-treated patients because of the presence of excessive clozapine with muscarinic antagonist activity. [ABSTRACT FROM AUTHOR]

Little is known about the mechanisms of unconsciousness induced by general anesthetics. Previous studies have shown that the primary somatosensory cortex (S1) is a sensitive region to a variety of intravenous general anesthetics. Etomidate is a widely used intravenous anesthetic that can influence synaptic transmission. Recently, there are some evidences suggesting that astrocytes, a type of glia cell, also contribute to information transmission in the brain, and modulate synaptic function by releasing neuroactive substances. However, it is unknown whether astrocytes influence the effects of etomidate on information transmission in S1 pyramidal neurons. In the present study, the role of astrocytes in etomidate-induced unconsciousness was investigated by using the whole-cell patch clamp technique. We observed etomidate at clinically relevant concentrations inhibited the spontaneous postsynaptic currents (sPSCs) of rat S1 pyramidal neurons in a concentration-dependent manner, and the EC50 value of etomidate for inhibiting sPSCs from the concentration-effect curve was 6.9 μM. Furthermore, in the presence of fluorocitrate, a glia-selective metabolism inhibitor that blocks the aconitase enzyme, both the amplitude and frequency of sPSCs in rat S1 pyramidal neurons were reduced, and the inhibitory effects of etomidate on sPSCs amplitude was strengthened without affecting the effects of etomidate on frequency. From these data, we deduce that etomidate suppresses synaptic activity via presynaptic and postsynaptic components. Furthermore, astrocytes participate in synaptic transmission and influence the effects of etomidate on postsynaptic receptors. This study provides new insight into the role of astrocytes in etomidate-induced unconsciousness. [ABSTRACT FROM AUTHOR]

Computational models of word recognition already successfully used associative spreading from orthographic to semantic levels to account for false memories. But can they also account for semantic effects on event-related potentials in a recognition memory task? To address this question, target words in the present study had either many or few semantic associates in the stimulus set. We found larger P200 amplitudes and smaller N400 amplitudes for old words in comparison to new words. Words with many semantic associates led to larger P200 amplitudes and a smaller N400 in comparison to words with a smaller number of semantic associations. We also obtained inverted response time and accuracy effects for old and new words: faster response times and fewer errors were found for old words that had many semantic associates, whereas new words with a large number of semantic associates produced slower response times and more errors. Both behavioral and electrophysiological results indicate that semantic associations between words can facilitate top-down driven lexical access and semantic integration in recognition memory. Our results support neurophysiologically plausible predictions of the Associative Read-Out Model, which suggests top-down connections from semantic to orthographic layers. [ABSTRACT FROM AUTHOR]

NG2 + glial cells are a dynamic population of non-neuronal cells that give rise to myelinating oligodendrocytes in the central nervous system. These cells express numerous ion channels and neurotransmitter receptors, which endow them with a complex electrophysiological profile that is unique among glial cells. Despite extensive analysis of the electrophysiological properties of these cells, relatively little was known about the molecular identity of the channels and receptors that they express. The generation of new RNA-Seq datasets for NG2 + cells has provided the means to explore how distinct genes contribute to the physiological properties of these progenitors. In this review, we systematically compare the results obtained through RNA-Seq transcriptional analysis of purified NG2 + cells to previous physiological and molecular studies of these cells to define the complement of ion channels and neurotransmitter receptors expressed by NG2 + cells in the mammalian brain and discuss the potential significance of the unique physiological properties of these cells. This article is part of a Special Issue entitled SI:NG2-glia(Invited only) . [ABSTRACT FROM AUTHOR]

Electrophysiological studies have strongly implicated theta-band activity in human working memory processes. Concurrently, work on spontaneous, non-task-related oscillations has revealed the presence of long-range temporal correlations (LRTCs) within sub-bands of the ongoing EEG, and has begun to demonstrate their functional significance. However, few studies have yet assessed the relation of LRTCs (also called scaling relations) to individual differences in cognitive abilities. The present study addressed the intersection of these two literatures by investigating the relation of narrow-band EEG scaling relations to individual differences in working memory ability, with a particular focus on the theta band. Fifty-four healthy adults completed standardized assessments of working memory and separate recordings of their spontaneous, non-task-related EEG. Scaling relations were quantified in each of the five classical EEG frequency bands via the estimation of the Hurst exponent obtained from detrended fluctuation analysis. A multilevel modeling framework was used to characterize the relation of working memory performance to scaling relations as a function of general scalp location in Cartesian space. Overall, results indicated an inverse relationship between both delta and theta scaling relations and working memory ability, which was most prominent at posterior sensors, and was independent of either spatial or individual variability in band-specific power. These findings add to the growing literature demonstrating the relevance of neural LRTCs for understanding brain functioning, and support a construct- and state-dependent view of their functional implications. [ABSTRACT FROM AUTHOR]

The brain hosts a primitive number sense to non-symbolically represent numerosities of objects or events. Small exact numerosities (~4 or less) can be individuated in parallel. In contrast, large numerosities (more than ~4) can only be approximated. However, whether small numerosities can be approximated without their parallel individuation remains unclear. Parallel individuation is suggested to be an attentive process and numerical approximation an automatic process. We, therefore, tested whether small numerosities can be represented preattentively. We recorded adult humans׳ event-related potentials (ERPs) and behavioral responses to 300-ms sequences of six tones (each of either 440 Hz or 660 Hz in frequency). Mostly, a sequence was of 3 tones of each frequency. Occasionally ( P =0.1), the numerosities were 4 and 2 (minor changes) or 5 and 1 (major changes). Mismatch negativity (MMN), but no later attention-related positive-polarity ERPs, was observed to the major but not to the minor changes during a visual non-numerical task. In a following attentive task, behavioral responses even to major changes resulted in a very low hit rates (0.11 for major and 0.023 for minor changes) and yet an above-zero false-alarm rate (0.052). The findings support a view that small numerosities of objects can be automatically approximated independently of their attentive individuation. [ABSTRACT FROM AUTHOR]

The specificity or generality of language-related event-related brain potentials (ERPs) has been a point of continuing debate in the cognitive neuroscience of language. The present study measured ERPs to (preferred) subject-before-object (SO) and (dispreferred) object-before-subject (OS) word orders in German while manipulating morphosyntactic and semantic cues to correct sentence interpretation. We presented sentence pairs as connected speech (context and target sentences) and examined ERPs at the position of the first argument (noun phrase) in the target sentence. At this position, word order was determinable by either (a) case marking (morphosyntactic cue); (b) animacy (semantic cue); or (c) the preceding context sentence (local ambiguity; contextual cue). Following each sentence pair, participants judged the acceptability of the second sentence in the context of the first and performed a probe word recognition task. Results showed a biphasic N400–P600 pattern at the first noun phrase in the OS conditions irrespectively of which cues (syntactic or semantic) were available to the parser for disambiguation. N400 latency varied as a function of temporal cue availability and P600 amplitude increased for unambiguous object-initial conditions even though these were rated acceptable in the judgment task. These findings support an interpretation of ERP components in terms of general cognitive mechanisms such as predictive processes (N400) and decision certainty (P600 as an instance of the P300) rather than a domain-specific view of a semantic N400 and a syntactic P600. [ABSTRACT FROM AUTHOR]

Involuntary switching of attention to distracting sounds was studied by measuring effects of these events on auditory discrimination performance and event-related brain potentials (ERPs) in 6–11-year-old boys with Attention Deficit – Hyperactivity Disorder (ADHD) and comorbid Oppositional Defiant Disorder (ODD) and in age-matched controls. The children were instructed to differentiate between two animal calls by pressing one response button, for example, to a dog bark and another button to a cat mew. These task-relevant sounds were presented from one of two loudspeakers in front of the child, and there were occasional task-irrelevant changes in the sound location, that is, the loudspeaker. In addition, novel sounds (e.g., a sound of hammer, rain, or car horn) unrelated to the task were presented from a loudspeaker behind the child. The percentage of correct responses was lower for target sounds preceded by a novel sound than for targets not preceded by such sound in the ADHD group, but not in the control group. In both groups, a biphasic positive P3a response was observed in ERPs to the novel sounds. The later part of the P3a appeared to continue longer over the frontal scalp areas in the ADHD group than in the controls presumably because a reorienting negativity (RON) ERP response following the P3a was smaller in the ADHD group than in the control group. This suggests that the children with ADHD had problems in reorienting their attention to the current task after a distracting novel sound leading to deterioration of performance in this task. The present study also indicates that children with ADHD and comorbid ODD show same kind of distractibility as found in previous studies for children with ADHD without systematic comorbid ODD. [ABSTRACT FROM AUTHOR]

Rapid advances are occurring in neural engineering, bionics and the brain–computer interface. These milestones have been underpinned by staggering advances in micro-electronics, computing, and wireless technology in the last three decades. Several cortically-based visual prosthetic devices are currently being developed, but pioneering advances with early implants were achieved by Brindley followed by Dobelle in the 1960s and 1970s. We have reviewed these discoveries within the historical context of the medical uses of electricity including attempts to cure blindness, the discovery of the visual cortex, and opportunities for cortex stimulation experiments during neurosurgery. Further advances were made possible with improvements in electrode design, greater understanding of cortical electrophysiology and miniaturisation of electronic components. Human trials of a new generation of prototype cortical visual prostheses for the blind are imminent. This article is part of a Special Issue entitled Hold Item . [ABSTRACT FROM AUTHOR]

This study investigated age-related differences in electrophysiological signatures of sequential modulations of poorer strategy effects. Sequential modulations of poorer strategy effects refer to decreased poorer strategy effects (i.e., poorer performance when the cued strategy is not the best) on current problem following poorer strategy problems compared to after better strategy problems. Analyses on electrophysiological (EEG) data revealed important age-related changes in time, frequency, and coherence of brain activities underlying sequential modulations of poorer strategy effects. More specifically, sequential modulations of poorer strategy effects were associated with earlier and later time windows (i.e., between 200- and 550 ms and between 850- and 1250 ms). Event-related potentials (ERPs) also revealed an earlier onset in older adults, together with more anterior and less lateralized activations. Furthermore, sequential modulations of poorer strategy effects were associated with theta and alpha frequencies in young adults while these modulations were found in delta frequency and theta inter-hemispheric coherence in older adults, consistent with qualitatively distinct patterns of brain activity. These findings have important implications to further our understanding of age-related differences and similarities in sequential modulations of cognitive control processes during arithmetic strategy execution. [ABSTRACT FROM AUTHOR]

Learned associations between drugs and environment play an important role in addiction and are thought to be encoded within specific patterns of sparsely distributed neurons called neuronal ensembles. This hypothesis is supported by correlational data from in vivo electrophysiology and cellular imaging studies in relapse models in rodents. In particular, cellular imaging with the immediate early gene c-fos and its protein product Fos has been used to identify sparsely distributed neurons that were strongly activated during conditioned drug behaviors such as drug self-administration and context- and cue-induced reinstatement of drug seeking. Here we review how Fos and the c-fos promoter have been employed to demonstrate causal roles for Fos-expressing neuronal ensembles in prefrontal cortex and nucleus accumbens in conditioned drug behaviors. This work has allowed identification of unique molecular and electrophysiological alterations within Fos-expressing neuronal ensembles that may contribute to the development and expression of learned associations in addiction. This article is part of a Special Issue entitled SI:Addiction circuits . [ABSTRACT FROM AUTHOR]

The addictive power of drugs of abuse such as cocaine comes from their ability to hijack natural reward and plasticity mechanisms mediated by dopamine signaling in the brain. Reward learning involves burst firing of midbrain dopamine neurons in response to rewards and cues predictive of reward. The resulting release of dopamine in terminal regions is thought to act as a teaching signaling to areas such as the prefrontal cortex and striatum. In this review, we posit that a pool of extrasynaptic dopaminergic D1-like receptors activated in response to dopamine neuron burst firing serve to enable synaptic plasticity in the prefrontal cortex in response to rewards and their cues. We propose that disruptions in these mechanisms following chronic cocaine use contribute to addiction pathology, in part due to the unique architecture of the mesocortical pathway. By blocking dopamine reuptake in the cortex, cocaine elevates dopamine signaling at these extrasynaptic receptors, prolonging D1-receptor activation and the subsequent activation of intracellular signaling cascades, and thus inducing long-lasting maladaptive plasticity. These cellular adaptations may account for many of the changes in cortical function observed in drug addicts, including an enduring vulnerability to relapse. Therefore, understanding and targeting these neuroadaptations may provide cognitive benefits and help prevent relapse in human drug addicts. This article is part of a Special Issue entitled SI:Addiction circuits . [ABSTRACT FROM AUTHOR]

• Efficient perception of auditory alarms is essential in safety-critical contexts. • Miss rate drastically increased with high mental and auditory loads. • P3b amplitude indexed mental and auditory loads variations. • P3b amplitude was anti-correlated with individual alarm miss rate. • Auditory alarm efficiency could be assessed with P3b measures. The ability to react to unexpected auditory stimuli is critical in complex settings such as aircraft cockpits or air traffic control towers, characterized by high mental load and highly complex auditory environments (i.e., many different auditory alerts). Evidence shows that both factors can negatively impact auditory attention and prevent appropriate reactions. In the present study, 60 participants performed a simulated aviation task varying in terms of mental load (no, low, high) concurrently to a tone detection paradigm in which the complexity of the auditory environment (i.e., auditory load) was manipulated (1, 2 or 3 different tones). We measured both detection performance (miss, false alarm, d') and brain activity (event-related potentials) associated with the target tone. Our results showed that both mental and auditory loads affected target tone detection performance. Importantly, their combined effects had a large impact on the percentage of missed target tones. While, in the no mental load condition, miss rate was very low with 1 (0.53%) and 2 tones (1.11%), it increased drastically with 3 tones (24.44%), and this effect was accentuated as mental load increased, yielding to the higher miss rate in the 3-tone paradigm under high mental load conditions (68.64%). Increased mental and auditory loads and miss rates were associated with disrupted brain responses to the target tone, as shown by a reduced P3b amplitude. In sum, our results highlight the importance of balancing mental and auditory loads to maintain efficient reactions to alarms in complex working environment. [ABSTRACT FROM AUTHOR]