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Neural synapses with diverse synaptic functions of short- and long-term plasticity are highly desired for developing complex neuromorphic systems. A memristor with its two terminals serving as pre- and post-neurons, respectively, can emulate two neuronal-based synaptic functions. In this work, multilayer two-dimensional (2D) layered WSe2 nanosheets are synthesized by a salt-assisted chemical vapor deposition (CVD) method. Two-terminal memristors with a planar structure are fabricated based on the CVD-grown triangular WSe2 nanosheets. The fabricated devices exhibit typical bipolar nonvolatile resistive switching behaviors with a high current ON/OFF ratio of up to 6 × 103 and good retention and endurance properties, suggesting good stability and reliability of the WSe2-based memristors. Furthermore, the developed memristors demonstrate synaptic functions of short- and long-term plasticity (STP and LTP), as well as a transition from STP to LTP by applying consecutive pulse voltages. Moreover, the WSe2-based memristors exhibits biological synaptic functions of long-term potentiation and depression, and paired-pulse facilitation. Thus, our 2D WSe2 nanosheet based memristors not only exhibit stable and reliable nonvolatile resistive switching behaviors, but also show potential applications in mimicking biological synapses.

Recent innovations in information technology have encouraged extensive research into the development of future generation memory and computing technologies. Memristive devices based on resistance switching are not only attractive because of their multi-level information storage, but they also display fascinating neuromorphic behaviors. We investigated the basic human brain’s learning and memory algorithm for “memorizing” as a feature for memristive devices based on Li-implanted structures with low power consumption. A topographical and surface chemical functionality analysis of an Li:ITO substrate was conducted to observe its characterization. In addition, a switching mechanism of a memristive device was theoretically studied and associated with ion migrations into a polymeric insulating layer. Biological short-term and long-term memory properties were imitated with the memristive device using low power consumption.

Summary A large number of experiments have indicated that precise spike times, firing rates, and synapse locations crucially determine the dynamics of long-term plasticity induction in excitatory synapses. However, it remains unknown how plasticity mechanisms of synapses distributed along dendritic trees cooperate to produce the wide spectrum of outcomes for various plasticity protocols. Here, we propose a four-pathway plasticity framework that is well grounded in experimental evidence and apply it to a biophysically realistic cortical pyramidal neuron model. We show in computer simulations that several seemingly contradictory experimental landmark studies are consistent with one unifying set of mechanisms when considering the effects of signal propagation in dendritic trees with respect to synapse location. Our model identifies specific spatiotemporal contributions of dendritic and axo-somatic spikes as well as of subthreshold activation of synaptic clusters, providing a unified parsimonious explanation not only for rate and timing dependence but also for location dependence of synaptic changes., Graphical Abstract, Highlights • A phenomenological synaptic plasticity rule is applied to a pyramidal neuron model • Model reproduces rate-, timing-, and location-dependent plasticity results • Active dendrites allow plasticity via dendritic spikes and subthreshold events • Cooperative plasticity exists across the dendritic tree and within single branches, Synaptic plasticity is shaped by local dynamic processes within dendritic trees. Ebner et al. present a biologically inspired plasticity rule and study its implications in a detailed model of a pyramidal cell. They provide a unified description of rate, timing, and location dependence and predict cooperative plasticity in dendrites.

Synapses between neurons are malleable biochemical structures, strengthening and diminishing over time dependent on the type of information they receive. This phenomenon known as synaptic plasticity underlies learning and memory, and its different forms, Long-Term Potentiation (LTP) and Long-Term Depression (LTD) perform varied cognitive roles in reinforcement, relearning and associating memories. Moreover, both LTP and LTD can exist in an early transient form (early-LTP/LTD) or a late persistent form (late-LTP/LTD), which are triggered by different induction protocols, and also differ in their dependence on protein synthesis and the involvement of key molecular players. Beyond homosynaptic modifications, synapses can also interact with one another. This is encapsulated in the Synaptic Tagging and Capture hypothesis (STC), where synapses expressing early-LTP/LTD present a 'tag' that can capture the protein synthesis products generated during a temporally proximal late-LTP/LTD induction. This 'tagging' phenomenon forms the framework of synaptic interactions in various conditions, and accounts for the cellular basis of the time-dependent associativity of short-lasting and long-lasting memories. All these synaptic modifications take place under controlled neuronal conditions, regulated by subcellular elements such as epigenetic regulation, proteasomal degradation and neuromodulatory signals. Here, we review current understanding of the different forms of synaptic plasticity and its regulatory mechanisms in the hippocampus, a brain region critical for memory formation. We also discuss expression of plasticity in hippocampal CA2 area, a long-overlooked narrow hippocampal subfield, and the behavioural correlate of STC. Lastly, we put forth perspectives for an integrated view of memory representation in synapses.

Synaptic plasticity, specifically long-term potentiation (LTP) and long-term depression (LTD), are well-established correlates of memory processes. The manipulation of NMDA receptors, which are critically involved in these forms of synaptic plasticity, offer a promising and thus frequently used means to gain new insight into the mechanisms of memory. Here, I investigated if the application of the NMDA receptor coagonist d-cycloserine (DCS) during consolidation affected subsequent learning in a sleep deprivation setting. To this end I administered DCS (vs. placebo) shortly after an initial word pair association task and measured the effect on subsequent learning of a similar task after DCS had reached negligible plasma levels. Assessing the indirect DCS effect on subsequent learning, allows to infer the effect of DCS on consolidation of the initial task. I hypothesised that enhanced or reduced subsequent learning performance would result from enhanced or reduced proactive interference from the initial memory task. In the current study subsequent learning was enhanced by DCS, suggesting decreased proactive interference. Such decreased interference could be brought about if DCS enhanced LTD. A related, methodologically identical study found similarly enhanced new learning under normal sleep settings. Together, this suggests that the LTD-enhancing effect of DCS is independent of the behavioural state (sleep vs wake). By contrast, an earlier study suggests that recall performance of the initial memory task is enhanced by DCS sleep dependently. Taken together these studies show the interesting pattern of sleep dependent enhancement of consolidation and sleep independent enhancement of subsequent learning. A possible explanation is, that DCS enhanced LTD, supporting homeostatic synaptic downregulation and thereby diminishing proactive interference with the subsequent task, independent of the behavioural state. In contrast, DCS induced enhancement of LTP may rely on sleep dependent processes, such as sleep dependent synaptic reactivations during active system consolidation. This is in line with previous studies and accounts suggesting that NMDA receptor activation has the potential to induce LTP and LTD, respectively, and that the direction of long term plasticity is in part dependent on the previous activity of the respective synapses. The data presented in this work together with the data of the related sleep study have been published in: Alizadeh Asfestani, M., Braganza E., Schwidetzky, J., Santiago, J., Soekadar, S., Born, J. & Feld, G. 2018. Overnight memory consolidation facilitates rather than interferes with new learning of similar materials – a study probing NMDA receptors. Neuropsychopharmacology, 43, 2292 – 2298.

BackgroundCombining training or sensory stimulation with non-invasive brain stimulation has shown to improve performance in healthy subjects and improve brain function in patients after brain injury. However, the plasticity mechanisms and the optimal parameters to induce long-term and sustainable enhanced performance remain unknown.ObjectiveThis work was designed to identify the protocols of which combining sensory stimulation with repetitive transcranial magnetic stimulation (rTMS) will facilitate the greatest changes in fMRI activation maps in the rat’s primary somatosensory cortex (S1).MethodsSeveral protocols of combining forepaw electrical stimulation with rTMS were tested, including a single stimulation session compared to multiple, daily stimulation sessions, as well as synchronous and asynchronous delivery of both modalities. High-resolution fMRI was used to determine how pairing sensory stimulation with rTMS induced short and long-term plasticity in the rat S1.ResultsAll groups that received a single session of rTMS showed short-term increases in S1 activity, but these increases did not last three days after the session. The group that received a stimulation protocol of 10 Hz forepaw stimulation that was delivered simultaneously with 10 Hz rTMS for five consecutive days demonstrated the greatest increases in the extent of the evoked fMRI responses compared to groups that received other stimulation protocols.ConclusionsOur results provide direct indication that pairing peripheral stimulation with rTMS induces long-term plasticity, and this phenomenon appears to follow a time-dependent plasticity mechanism. These results will be important to lead the design of new training and rehabilitation paradigms and training towards achieving maximal performance in healthy subjects.HighlightsA single rTMS session induced short-term changes but they were not sustainableMulti-session delivery of rTMS paired with sensory stimulation induced long-term plasticityrTMS paired with sensory stimulation induced plasticity via time-dependent mechanismDelivery of sensory stimulation only did not induce long-term plasticity

Sleep is an ancient and fundamental animal behavior. Sleep deprivation builds up sleep need to trigger recovery sleep, a homeostatic control crucial to maintain cognitive performance. Between several suggestions to explain the indispensable nature of sleep, restoration of synapse plasticity is a prominent one, though causal relations here remained scarce. In this review, we will discuss recent advances reporting a mutual functional interplay between sleep deprivation-associated synaptic changes and sleep homeostasis.

It is unclear to what extent cerebellar networks show long-term plasticity and accompanied changes in cortical structures. Using drumming as a demanding multimodal motor training, we compared cerebellar lobular volume and white matter microstructure, as well as cortical thickness of 15 healthy non-musicians before and after learning to drum, and 16 age matched novice control participants. After 8 weeks of group drumming instruction, 3 ×30 minutes per week, we observed the cerebellum significantly changing its grey (volume increase of left VIIIa, relative decrease of VIIIb and vermis Crus I volume) and white matter microstructure in the inferior cerebellar peduncle. These plastic cerebellar changes were complemented by changes in cortical thickness (increase in left paracentral, right precuneus and right but not left superior frontal thickness), suggesting an interplay of cerebellar learning with cortical structures enabled through cerebellar pathways.

Schizophrenia patients have widespread deficits in neurocognitive functioning linked to underlying abnormalities in gamma oscillations that are readily measured by the 40 Hz auditory steady-state response (ASSR). Emerging interventions such as auditory-based targeted cognitive training (TCT) improve neurocognitive function in patients. While acute ASSR changes after 1 hour of TCT predict clinical and cognitive gains after a 30-hour course of TCT, the neural substrates of underlying short- and long-term TCT interventions are unknown. To determine the neural substrates underlying TCT-associated ASSR changes, a novel data analysis method was applied to assess the effective connectivity of gamma-band ASSR among estimated cortical sources. In this study, schizophrenia patients (N = 52) were randomized to receive either a treatment as usual (TAU; N = 22) or TAU augmented with TCT (N = 30). EEG recordings were obtained immediately before (T0) and after 1 hour of either computer games (TAU) or cognitive training (TCT; T1), and at 65 ± 15 days (mean ± SD) post-randomization (T2). Results showed increased connectivity from the left ventral middle cingulate gyrus to the left posterior cingulate gyrus, accompanied by decreased connectivity from the left Rolandic operculum (a region that includes auditory cortex) to the right ventral middle cingulate gyrus after 1 hour of TCT. After 30 hours, decreased connectivity from the frontal cortex to a region near the calcarine sulcus were detected. Auditory-based cognitive training drives short- and long-term plasticity in cortical network functioning in schizophrenia patients. These findings may help us understand the mechanisms underlying cognitive training effects in schizophrenia patients and enhance the development of pro-cognitive therapeutics.

The electronic synapse, which can vividly emulate short-term and long-term plasticity, as well as voltage sensitivity, in the bio-synapse, is the vital device foundation for brain-inspired neuromorphic computing. In this letter, we propose a Ag/GeSe/TiN memristor as an electronic synapse for brain-inspired neuromorphic applications. Due to the electromigration and diffusion of Ag cation, the volatile and non-volatile switching behaviours are coexistent in this device. Various synaptic functions, including short-term plasticity, long-term plasticity, pair-pulse facilitation, and spike timing-dependent plasticity, have been successfully eliminated in Ag/GeSe/TiN devices. Furthermore, all the synaptic functions are induced by the spiking stimuli with amplitudes of several hundred millivolts. All the results demonstrate that the Ag/GeSe/TiN device has great potential for brain-inspired computing systems in the future.

Short-term plasticity and long-term plasticity of bio-synapse are thought to underpin critical physiological functions in neural circuits. In this letter, we vividly emulated the short-term and long-term synaptic functions in a single Cu/a-Si/Pt memristor. By controlling the injection quantity of Cu cations into the a-Si layer, the device showed volatile and non-volatile resistive switching behaviors. Owing to the unique characteristics of Cu/a-Si/Pt device, the short-term synaptic functions, i.e., short-term potentiation, pair-pulse facilitation, and long-term functions, i.e., long-term potentiation/depression, spike-timing-dependent plasticity, were mimicked in the memristor successfully. Furthermore, the transition from short-term memory to long-term memory of the device was also observed under repeated stimuli. The experimental results confirm that the Cu/a-Si/Pt memristor with various synaptic behaviors has a potential application in the brain-inspired computing systems.

We have studied alterations in the properties of long-term potentiation (LTP) in hippocampal slices of juvenile rats induced by the exposure of animals to different individual stressors usually used in batteries of chronic unpredictable stress (CUS), a widely used model of depression. Social isolation for 16 h did substantially affect neither the magnitude and nor the development of LTP. The effects of stroboscopic illumination and water deprivation appeared most severe, though opposite: the first stressor had activating effect, whereas the second one inhibited the development of LTP. In addition to the effects of these factors on the LTP magnitude, they also affected the patterns of LTP development. In this study weak tetanization with different probability of maintenance was used, and most of stressors, in spite of the similar LTP magnitude, influenced significantly on the process of consolidation. In hippocampal slices from rats maintained on wet bedding for 16 h, the time course but not magnitude of LTP significantly differed from that observed in the control or socially isolated rats. The weakest effect on LTP was observed in hippocampal slices of the rats exposed to food deprivation. In these animals, only some differences were observed in the development of LTP as compared to socially isolated rats. These data allow ranging stressors used in CUS paradigms according to the severity of their potential effects on neuronal function and animal behavior.

Activated by action potentials and Ca2+ ion migration, neurotransmitters in biological synapses are released from vesicles at the presynaptic membrane to the cleft and bonded to receptors on the postsynaptic membrane. The bonded neurotransmitters modify the electrochemical properties of the postsynaptic membrane and, thereby, the synaptic plasticity, which forms the basis for learning, memory, emotion, cognition, and consciousness. Here, the oxygen vacancy transport in Au/SrTiO3 (STO)/La0.67Sr0.33MnO3 (LSMO) tunnel junctions is exploited to mimic neurotransmission processes in an artificial ionic electronic device. Using voltage pulses of varying number, amplitude, and polarity, it is demonstrated that reversible oxygen vacancy migration across the STO/LSMO interface provides stable multilevel resistance switching for octal memory devices and resembles the quantal, stochastic, and excitatory or inhibitory nature of neurotransmitter release dynamics. Moreover, fundamental synaptic behaviors including long‐term potentiation/depression and various types of spike‐timing‐dependent plasticity characteristics are emulated, opening a promising biorealistic approach to the design of neuromorphic devices.

In this study, a new experimental protocol to evaluate long-term, plasticity-controlled failure using short-term testing is validated on a high-density polyethylene (PE100) pipe grade. The protocol starts with the assessment of the strain rate dependence of the yield stress in uniaxial extension at various temperatures. Additional uniaxial compression tests are performed to characterize the influence of hydrostatic stress. The plastic flow kinetics are subsequently captured using a Ree-Eyring modification of the pressure-modified Eyring flow equation. In combination with the hypothesis that failure occurs at a critical amount of accumulated plastic strain, a versatile tool to predict time-to-failure is obtained. POLYM. ENG. SCI., 56:676–688, 2016. © 2016 Society of Plastics Engineers

Synaptic efficacy is subjected to activity-dependent changes on short- and long time scales. While short-term changes decay over minutes, long-term modifications last from hours up to a lifetime and are thought to constitute the basis of learning and memory. Both plasticity mechanisms have been studied extensively but how their interaction shapes synaptic dynamics is little known. To investigate how both short- and long-term plasticity together control the induction of synaptic depression and potentiation, we used numerical simulations and mathematical analysis of a calcium-based model, where pre- and postsynaptic activity induces calcium transients driving synaptic long-term plasticity. We found that the model implementing known synaptic short-term dynamics in the calcium transients can be successfully fitted to long-term plasticity data obtained in visual- and somatosensory cortex. Interestingly, the impact of spike-timing and firing rate changes on plasticity occurs in the prevalent firing rate range, which is different in both cortical areas considered here. Our findings suggest that short- and long-term plasticity are together tuned to adapt plasticity to area-specific activity statistics such as firing rates., Author summary Synaptic long-term plasticity, the long-lasting change in efficacy of connections between neurons, is believed to underlie learning and memory. Synapses furthermore change their efficacy reversibly in an activity-dependent manner on the subsecond time scale, referred to as short-term plasticity. It is not known how both synaptic plasticity mechanisms—long- and short-term—interact during activity epochs. To address this question, we used a biologically-inspired plasticity model in which calcium drives changes in synaptic efficacy. We applied the model to plasticity data from visual- and somatosensory cortex and found that synaptic changes occur in very different firing rate ranges, which correspond to the prevalent firing rates in both structures. Our results suggest that short- and long-term plasticity act in a well concerted fashion.

In recent years self organised critical neuronal models have provided insights regarding the origin of the experimentally observed avalanching behaviour of neuronal systems. It has been shown that dynamical synapses, as a form of short-term plasticity, can cause critical neuronal dynamics. Whereas long-term plasticity, such as hebbian or activity dependent plasticity, have a crucial role in shaping the network structure and endowing neural systems with learning abilities. In this work we provide a model which combines both plasticity mechanisms, acting on two different time-scales. The measured avalanche statistics are compatible with experimental results for both the avalanche size and duration distribution with biologically observed percentages of inhibitory neurons. The time-series of neuronal activity exhibits temporal bursts leading to 1/f decay in the power spectrum. The presence of long-term plasticity gives the system the ability to learn binary rules such as XOR, providing the foundation of future research on more complicated tasks such as pattern recognition., 8 pages, 7 figures

Research in neuroscience relies to a large extent on the use of genetically modified animals. Extensive validation of new and existing models is a requirement for the acquisition of trustworthy data and to enable generalization to human physiology and disease. This thesis includes, as one part (project I and II), validation of a transgenic mouse model with the expression of the enzyme Cre-recombinase restricted to neurons in a band in the deepest layer of the cerebral cortex. Secondly, in project III we use this mouse model to study the process of short-term plasticity in neuronal cultures. Lastly, we investigate synaptic plasticity by studying the effect that the developmental signaling factor Hedgehog (Hh) has on mature hippocampal cultures (project IV). In project I and II, we identified the transgenic mouse Neurotensin receptor 1-Cre GN220 (Ntsr1-Cre) to have Cre expression targeted to the corticothalamic (CT) pyramidal neuron population in neocortical layer 6. Further, we identified a small group of Ntsr1-Cre positive neurons present in the white matter that is distinct from the CT population. We also identified that the transcription factor Forkhead box protein 2 (FoxP2) was specifically expressed by CT neurons in neocortex. In project I, we further explored the sensitivity of CT neurons to cholinergic modulation and found that they are sensitive to even low concentrations of acetylcholine. Both nicotinic and muscarinic acetylcholine receptors depolarize the neurons. Presenting CT neurons as a potential target for cholinergic modulation in wakefulness and arousal. In project III we studied Ntsr1-Cre neurons in cortical cultures and found that cultured neurons have similar properties to CT neurons in the intact nervous system. Ntsr1-Cre neurons in culture often formed synapses with itself, i. e. autapses, with short-term synaptic plasticity that was different to ordinary synapses. By expressing the light-controlled ion channel channelrhodopsin-2 (ChR2) in Ntsr1-Cre neurons we could compare paired pulse ratios with either electrical or light stimulation. Electrical stimulation typically produced paired-pulse facilitation while light stimulation produced paired pulse depression, presumably due to unphysiological Ca2+ influx in presynaptic terminals. Thus, cultured Ntsr1- Cre neurons can be used to study facilitation, and ChR2 could be used as a practical tool to further study the dependence of Ca2+ for short-term plasticity. In project IV we investigated the role of Hedgehog (Hh) for hippocampal neuron plasticity. Non-canonical Hh-signaling negatively regulated NMDA- receptor function through an unknown mechanism resulting in changes in NMDA-receptor mediated currents and subsequent changes in AMPA- receptors in an LTP/LTD manner in mature neurons. Proposing Hh as a slow-acting factor with ability to scale down excitation for instances of excessive activity, e.g. during an epileptic seizure, as a mechanism to make the activity in the neuronal networks stable.

Existence of spontaneous population bursts is a widely studied phenomenon observed in neuronal cultures in vitro. Recent models of neuronal cultures network activity consist of a number of burst generating mechanisms such as synaptic noise and presence of pacemaker neurons in the network. In the previous simulations of bursting in neuronal cultures synaptic weights change in accordance with the rule of short-term plasticity whereas the long-term values of them, and hence the network structure, remain unchanged. In this paper we reproduce neuronal network models with static synapses, and then investigate spontaneous activity changes in neuronal networks with long-term plasticity defined by STDP rule. Our results demonstrate that introduction of long-term plasticity in the model leads to discrepancy with the experimental data.

Dopamine (DA) modulates glutamatergic synaptic transmission and its plasticity in the striatum; however it is not well known how DA modulates long-term plasticity of striatal GABAergic inhibitory synapses. This work focused on the analysis of both dopaminergic modulation of inhibitory synapses and the synaptic plasticity established between GABAergic afferents to medium spiny neurons (MSNs). Our results showed that low and high DA concentrations mainly reduced the amplitude of inhibitory synaptic response; however detailed analysis of the D1 and D2 participation in this modulation displayed a wide variability in synaptic response. Analyzing DA participation in striatal GABAergic plasticity we observed that high frequency stimulation (HFS) of GABAergic interneurons in the presence of DA at a low concentration (200 nM) favored the expression of inhibitory striatal LTD, whereas higher concentration of DA (20 μM) primarily induced LTP. Interestingly, the plasticity induced in an animal model of striatal degeneration mimicked that induced in the presence of DA at a high concentration, which was not abolished with D2 antagonist but was prevented by PKA blocker.

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are assembled of four core subunits and several additional interacting proteins. Cystine-knot AMPA receptor-modulating proteins (CKAMPs) constitute a family of four proteins that influence the trafficking, subcellular localization and function of AMPA receptors. The four CKAMP family members CKAMP39/shisa8, CKAMP44/shisa9, CKAMP52/shisa6 and CKAMP59/shisa7 differ in their expression profile and their modulatory influence on AMPA receptor function. In this review, I report about recent findings on the differential roles of CKAMP family members.

In this chapter we will consider two main types of plasticity. First, we will discuss short-term plasticity, the modulation of synaptic strength on the time scale of milliseconds to seconds. Second, we will learn about long-term plasticity, long-lasting changes to synaptic strength that form the basis of learning and memory. We will learn about the rules that govern synaptic plasticity and introduce intuitive mathematical models of plasticity. The toolboxes Neurons, Differential Equations, and Dynamical Systems provide helpful background for this chapter.

Attention is known to be crucial for learning and to regulate activity-dependent brain plasticity. Here we report the opposite scenario, with plasticity affecting the onset-driven automatic deployment of spatial attention. Specifically, we showed that attentional capture is subject to habituation, a fundamental form of plasticity consisting in a response decrement to repeated stimulations. Participants performed a visual discrimination task with focused attention, while being occasionally exposed to a distractor consisting of a high-luminance peripheral onset. With practice, short-term and long-term habituation of attentional capture emerged, making the visual-attention system fully immune to distraction. Furthermore, spontaneous recovery of attentional capture was found when the distractor was temporarily removed. Capture, however, once habituated was surprisingly resistant to spontaneous recovery, taking from several minutes to days to recover. The results suggest that the mechanisms subserving exogenous attentional orienting are subject to profound and enduring plastic changes based on previous experience, and that habituation can impact high-order cognitive functions.

The axon initial segment (AIS) is a highly specialized neuronal subregion that is the site of action potential initiation and the boundary between axonal and somatodendritic compartments. In recent years, our understanding of the molecular structure of the AIS, its maturation, and its multiple fundamental roles in neuronal function has seen major advances. We are beginning to appreciate that the AIS is dynamically regulated, both over short timescales via adaptations in ion channel function, and long timescales via activity-dependent structural reorganization. Here, we review results from this emerging field highlighting how structural and functional plasticity relate to the development of the initial segment, and to neuronal disorders linked to AIS dysfunction.

One of the biggest remaining mysteries of science is inside our heads: how does nature wire up a high-performance computer with­out having a detailed blueprint specifying the location and strength of every connection? It is assumed that local connectivity in our cor­tex is at first random, and during develop­ment undergoes refinement until only the ‘right’ connections are left over. But how can the brain tell ‘right’ from ‘wrong’ connections? The majority of excitatory connections are formed on dendritic spines, tiny excrescenc­es that cover almost the entire dendritic sur­face of most neurons. Since their discovery by Ramón y Cajal in 1896, neuroscientists have been fascinated by these structures, which ultimately determine which neurons in the brain become connected and form function­al networks. Here we review the many im­portant functions of spines and explain why electrical and biochemical processes in these tiny structures are thought to be crucial for the plasticity of the brain.

Resume Le role benefique du sommeil dans les processus d’apprentissage et de memoire est communement admis. La presente revue a pour but de clarifier ce role, en prenant comme exemple la consolidation, un des aspects les mieux etudies de la memoire. La consolidation est un processus dynamique qui protege les apprentissages recents des interferences et ameliore les performances apres une periode variable de quelques heures a plusieurs jours. Il a ete montre par plusieurs equipes que le sommeil facilitait la consolidation de la memoire declarative et procedurale. Cependant, les roles respectifs du sommeil a ondes lentes (SL) du sommeil paradoxal (SP) apparaissent bien differents. La consolidation de phenomenes mnesiques impliquant l’hippocampe (memoire declarative) est facilitee par le sommeil a ondes lentes. Le sommeil paradoxal, quant a lui, augmente les performances mnesiques pour des tâches d’apprentissage procedural ou l’hippocampe est peu ou pas implique. Des approches interdisciplinaires chez l’homme et l’animal amenent a suggerer des hypotheses quant aux mecanismes de memoire regules par le SL et SP. Le SL pourrait constituer une periode privilegiee, depourvue de changements plastiques, qui protege des interferences et permet le transfert d’informations entre hippocampe et neocortex. A l’inverse, le SP serait une phase ou les echanges entre aires corticales sont restreints mais ou des reorganisations synaptiques de longue duree a l’echelle neuronale pourraient constituer un support de la consolidation.

GABAA receptor (GABA-AR)-mediated inhibition is critical for proper operation of neuronal networks. Synaptic inhibition either shifts the membrane potential farther away from the action potential firing threshold (hyperpolarizing inhibition) or via increase in the membrane conductance shunts the excitatory currents. However, the relative importance of these different forms of inhibition on the hippocampal function is unclear. To study the functional consequences of the absence of hyperpolarizing inhibition, we have used KCC2-deficient mice (KCC2hy/null) maintaining only 15–20% of the neuron-specific K-Cl-cotransporter. Gramicidin-perforated patch-clamp recordings in hippocampal CA1 pyramidal cells revealed that the reversal potential of the GABA-AR-mediated postsynaptic currents ( EGABA-A) was ∼20 mV more positive in KCC2hy/null mice than in wild-type (WT) animals. The basic glutamatergic transmission appeared unaltered in the KCC2hy/null mice, yet they displayed lowered threshold for stimulation-induced synchronous afterdischarges in the CA1 area. Also fatigue of field excitatory postsynaptic potentials/excitatory postsynaptic currents in response to repetitious stimulation was smaller in KCC2hy/null mice, indicating altered synaptic dynamics. Interestingly, this effect was present also under blockade of GABA-ARs and was dependent on the extracellular K+ concentration. Moreover, there were no differences in the levels of either long-term potentiation or long-term depression between the genotypes. The local hippocampal CA1 network can in several aspects maintain its functional viability even in the absence of hyperpolarizing inhibition in pyramidal cells. Our results underscore the central role of shunting type of inhibition in controlling the neuronal excitation/inhibition balance. Moreover, our data demonstrate a novel, unexpected role for the KCC2, namely the modulation of properties of glutamatergic transmission during repetitious afferent activity.

S1 long-term plasticity refers to persistent modifications in the structure or functioning of the primary somatosensory cortex (S1). These modifications are proposed to underlie learning and memory of tactile information, as well as recovery of function after injury.

The purpose of this research topic is to showcase recent anatomical, physiological, and clinical studies revealing how the cerebellum is embedded within distributed neural networks recruited during both direct motor functions plus cognitive and other domains. The topic comprises a total of 15 articles that together span experimental, theoretical, methodological approaches, and reviews of the literature.

A recent flurry of time-lapse imaging studies of live neurons have tried to address the century-old question: what morphological changes in dendritic spines can be related to long-term memory? Changes that have been proposed to relate to memory include the formation of new spines, the enlargement of spine heads and the pruning of spines. These observations also relate to a more general question of how stable dendritic spines are. The objective of this review is to critically assess the new data and to propose much needed criteria that relate spines to memory, thereby allowing progress in understanding the morphological basis of memory.

Unilateral labyrinthectomy results in oculomotor and postural disturbances that regress in a few days during vestibular compensation. The long-term (after 1 mo) consequences of unilateral labyrinthectomy were investigated by characterizing the static and dynamic membrane properties of the ipsilesional vestibular neurons recorded intracellularly in guinea pig brain stem slices. We compared the responses of type A and type B medial vestibular nucleus neurons identified in vitro to current steps and ramps and to sinusoidal currents of various frequencies. All ipsilesional vestibular neurons were depolarized by 6–10 mV at rest compared with the cells recorded from control slices. Both their average membrane potential and firing threshold were more depolarized, which suggests that changes in active conductances compensated for the loss of excitatory afferents. The afterhyperpolarization and discharge regularity of type B but not type A neurons were increased. All ipsilesional vestibular cells became more sensitive to current injections over a large range of frequencies (0.2–30 Hz), but this increase in sensitivity was greater for type B than for type A neurons. This was associated with an increase of the peak frequency of linear response restricted to type B neurons, from 4–6 to 12–14 Hz. Altogether, we show that long-term vestibular compensation involves major changes in the membrane properties of vestibular neurons on the deafferented side. Many of the static and dynamic membrane properties of type B neurons became more similar to those of type A neurons than in control slices, leading to an increase in the overall homogeneity of medial vestibular nucleus neurons.