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Among its significant reforms, the Uniform Power of Attorney Act (UPOAA) denies agents nine types of power unless “the power of attorney expressly grants” them. Those so-called “hot powers” relate to delegations of fiduciary authority and to donative transfers of the principal’s property for less than full consideration. The donative hot powers include creating, amending, or terminating a trust; making gifts; creating or changing beneficiary designations; creating or changing rights of survivorship; and waiving or disclaiming property interests. The rationale for requiring the grant of specific authority is the risk those acts pose to the principal’s property and estate plan. Although the UPOAA was approved fifteen years ago and thereafter adopted by about thirty U.S. jurisdictions, only a dozen or so judicial opinions address the donative hot powers, and some of them are “unpublished.” Consequently, while “uniformity of application and construction” is a goal of the UPOAA, the number and availability of authorities construing and applying the donative hot-powers provisions is limited. Within those judicial opinions dealing with donative hot powers, only the power to “make a gift” meaningfully has been considered. Regarding other donative hot powers, most notable is a failure of courts to recognize that transfers they have permitted agents to make required express authority that did not appear to exist. This Article analyzes fourteen donative hot-powers decisions. [ABSTRACT FROM AUTHOR]

Sole entrepreneurs overwhelmingly choose the single-member limited liability company (SMLLC) as the business entity for their operations. Consequently, simplicity of formation and operation of SMLLCs is highly desirable, both to facilitate entrepreneurship and to acknowledge that costs, lack of knowledge, bad advice, or a combination of them very often will cause sole entrepreneurs to forego professionally drafted documents and accept default SMLLC rules in the jurisdiction of formation. The death of the sole member is always an anticipated, indeed inevitable, occurrence, so one would expect that the default statutory rules and the widely available forms for SMLLCs would address this eventuality adequately. Unfortunately, that is not the case. In this Article, we address how SMLLC organizational documents should always address the death of the sole member of an SMLLC, and we conclude that a provision for the nonprobate transfer on death of the sole member's interest should be included. We also address the federal tax consequences of death-time transfers of SMLLC interests, and we uncover a thorny conflict between federal income taxes, which disregard the entity, and federal transfer taxes, which regard the entity. [ABSTRACT FROM AUTHOR]

When a transfer of real property creates a future interest in a party without expressly providing whether that party must survive all others in possession prior, the common law has traditionally refused to imply such a requirement. Recently, various reform movements have proposed reversing this rule. Where such a reversal fails to likewise negate the reversion created by the change, the transferor-possessor of the reversion faces complicated tax issues as a result. In this Article, the author provides an overview of the various attempts to reverse the rule and goes through the complicated actuarial mathematics that are required to assess the tax liability of the possessor of the reversion. [ABSTRACT FROM AUTHOR]

The amygdala is a highly connected cluster of nuclei with input from multiple sensory modalities, particularly the ventral visual stream, and vast projections to distributed cortical and subcortical regions involved in autonomic regulation and cognition. 1-4 Numerous studies have described the amygdala's capacity to facilitate the encoding of long-lasting emotional memories. 5-15 Recently, direct electrical stimulation of the basolateral complex of the amygdala (BLA) in humans revealed a more generalized ability to enhance declarative memory irrespective of the emotional valence 16 , likely by promoting synaptic plasticity-related processes underlying memory consolidation in the hippocampus and medial temporal lobe. 17-20 These effects were achieved with rhythmic theta-burst stimulation (TBS), which is known to induce long-term potentiation (LTP), a key mechanism in memory formation. 21 Emerging evidence suggests that intracranial TBS may also enhance memory specificity 22 , evoke theta-frequency oscillations 23 , and facilitate short-term plasticity in local field potential recordings. 24,25 However, how amygdalar TBS modulates activity at the single-cell level and to what extent this modulation is associated with memory performance remain poorly understood. Here, we address this knowledge gap by conducting simultaneous microelectrode recordings from prefrontal and medial temporal structures during a memory task in which intracranial TBS was applied to the BLA. We observed a subset of neurons whose firing rate was modulated by TBS and exhibited highly heterogeneous responses with respect to onset latency, duration, and direction of effect. Notably, location and baseline activity predicted which neurons were most susceptible to modulation. These findings provide direct empirical support for stimulation-evoked modulation of single-neuron activity in humans, which has implications for the development and refinement of neuromodulatory therapies., Competing Interests: Competing Interests None.

Objective. Single-pulse electrical stimulation (SPES) has been widely used to probe effective connectivity. However, analysis of the neural response is often confounded by stimulation artifacts. We developed a novel matching pursuit-based artifact reconstruction and removal method (MPARRM) capable of removing artifacts from stimulation-artifact-affected electrophysiological signals. Approach. To validate MPARRM across a wide range of potential stimulation artifact types, we performed a bench-top experiment in which we suspended electrodes in a saline solution to generate 110 types of real-world stimulation artifacts. We then added the generated stimulation artifacts to ground truth signals (stereoelectroencephalography signals from nine human subjects recorded during a receptive speech task), applied MPARRM to the combined signal, and compared the resultant denoised signal with the ground truth signal. We further applied MPARRM to artifact-affected neural signals recorded from the hippocampus while performing SPES on the ipsilateral basolateral amygdala in nine human subjects. Main results. MPARRM could remove stimulation artifacts without introducing spectral leakage or temporal spread. It accommodated variable stimulation parameters and recovered the early response to SPES within a wide range of frequency bands. Specifically, in the early response period (5-10 ms following stimulation onset), we found that the broadband gamma power (70-170 Hz) of the denoised signal was highly correlated with the ground truth signal (R=0.98±0.02, Pearson), and the broadband gamma activity of the denoised signal faithfully revealed the responses to the auditory stimuli within the ground truth signal with94%±1.47%sensitivity and99%±1.01%specificity. We further found that MPARRM could reveal the expected temporal progression of broadband gamma activity along the anterior-posterior axis of the hippocampus in response to the ipsilateral amygdala stimulation. Significance. MPARRM could faithfully remove SPES artifacts without confounding the electrophysiological signal components, especially during the early-response period. This method can facilitate the understanding of the neural response mechanisms of SPES., (Creative Commons Attribution license.)

The social behavior network (SBN) has provided a framework for understanding the neural control of social behavior. The original SBN hypothesis proposed this network modulates social behavior and should exhibit distinct patterns of neural activity across nodes, which correspond to distinct social contexts. Despite its tremendous impact on the field of social neuroscience, no study has directly tested this hypothesis. Thus, we assessed Fos responses across the SBN of male prairie voles (Microtus ochrogaster). Virgin/non-bonded and pair bonded subjects were exposed to a sibling cagemate or pair bonded partner, novel female, novel male, novel meadow vole, novel object, or no stimulus. Inconsistent with the original SBN hypothesis, we did not find profoundly different patterns of neural responses across the SBN for different contexts, but instead found that the SBN generated significantly different patterns of activity in response to social novelty in pair bonded, but not non-bonded males. These findings suggest that non-bonded male prairie voles may perceive social novelty differently from pair bonded males or that SBN functionality undergoes substantial changes after pair bonding. This study reveals novel information about bond-dependent, context-specific neural responsivity in male prairie voles and suggests that the SBN may be particularly important for processing social salience. Further, our study suggests there is a need to reconceptualize the framework of how the SBN modulates social behavior., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The amygdala and orbitofrontal cortex (OFC) are interconnected regions that serve as key nodes in brain circuits supporting social and affective behaviors. An important question that has come into focus is whether these regions also play a fundamental role in responding to novelty. One possibility is that these regions are important for discriminating novel from familiar stimuli. An alternative possibility is that these regions contribute to affective responses to stimuli in novelty-based tasks. For example, the amygdala and OFC could contribute to assessing novel stimuli as being threatening or previously selected stimuli as having reward value. The present study tested rhesus macaque monkeys with damage to the amygdala or OFC, along with sham-operated control monkeys, across six variants of novelty-based memory tasks. The results showed that monkeys with damage to the amygdala or OFC performed better overall than control monkeys across the tasks. The results indicated that neither region was essential for discriminating novel from familiar stimuli. Instead, the findings suggested that the improved performance observed in novelty-based tasks following damage to these regions was more likely attributable to influences on affect. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Tallman and colleagues (this issue) report fMRI findings in support of the classic view of memory consolidation over its main challenger, the multiple trace theory. The present commentary highlights some of the obstacles facing any fMRI study of memory consolidation and notes which challenges were tackled by Tallman and colleagues and which challenges might be insurmountable.

Objective: To assess whether diabetes alone or in association with Apolipoprotein E (APOE) ε4 genotype increases the risk of Alzheimer's Disease (AD) diagnosis. Methods: A retrospective cohort study of 33,456 participants from the National Alzheimer's Coordinating Center database. Results: Participants with one or two APOE ε4 alleles had 2.71 (CI:2.55-2.88) and 9.37 (CI:8.14-10.78) times higher odds of AD diagnosis, respectively, relative to those with zero ε4 alleles. In contrast, diabetic participants showed 1.07 (CI:0.96-1.18) times higher odds of AD relative to nondiabetics. Diabetes did not exacerbate the odds of AD in APOE ε4 carriers. APOE ε4 carriage was correlated with declines in long-term memory and verbal fluency, which were strongly correlated with conversion to AD. However, diabetes was correlated with working memory decline, which had a relatively weak correlation with AD. Conclusions: Unlike APOE ε4, there was little evidence that diabetes was a risk factor for AD.

The ability to generate new knowledge depends on integration of separate information. For example, in one episode an individual may learn that apple seeds are called pips. In a separate episode, the individual may then learn that pips contain cyanide. Integration of the related facts in memory may then support derivation of the new knowledge that apple seeds contain cyanide. Past studies show that adults form relational memories that represent the commonalities among discrete events, and that such integrated representation supports the ability to infer new knowledge. Although these integrated representations are thought to result from linking separate memories to the same neuronal ensemble, the neural mechanisms that underlie formation of such linkages are not well understood. Here we examined whether self-derivation of new, integrated knowledge was supported by oscillatory coherence, a means of linking discrete neuronal ensembles. Cortical alpha coherence was greater when adults encoded new facts that could be integrated with existing knowledge, relative to encoding unrelated facts, particularly in participants who showed better performance on the subsequent test of knowledge generation via fact integration. In high performers, posterior alpha amplitude was also modulated by delta phase, a form of cross-frequency coupling previously implicated in coordinating information stored widely throughout the cortex. Examination of the timing and topography of these respective signatures suggested that these oscillatory dynamics work in concert to encode and represent new knowledge with respect to prior knowledge that is reactivated, thus revealing fundamental mechanisms through which related memories are linked into integrated knowledge structures., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021. Published by Elsevier Inc.)

The amygdala is a collection of nuclei that support adaptive social behavior and are implicated in disorders such as autism. The basolateral complex of the amygdala (BLA), a main subdivision of the amygdala, influences fear responses, motivated behavior, and memory of emotional events via its communication with other amygdalar nuclei and with other brain regions such as the prefrontal cortex, striatum, and hippocampus. The specific role of the BLA in responses to social stimuli is less clear. The present study of female rats investigated the role of the BLA in responding to socially-relevant information by asking how inactivation of the BLA with bilateral infusions of the GABA receptor agonist muscimol would affect spontaneous exploration of wood blocks scented either with conspecific male or female urine or with nonsocial odorants. Conspecific urine samples were used because urine conveys information about sex, health, social status, and reproductive state in rodents. The results revealed that BLA inactivation reduced female rats' spontaneous preference for social odors over nonsocial odors, specifically for female urine. However, BLA inactivation did not generally impair rats' ability to distinguish two odors from the same category (e.g., urine odors from two different male rats). The results indicate that the BLA is important for responding to salience of social stimuli but not for discriminating between different individuals, a result that has important implications for amygdalar modulation of downstream attention, motivation, and memory processes for social stimuli., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The basolateral complex of the amygdala (BLA) is capable of modulating memory and is thought to do so via projections to regions such as the hippocampus. The present study used optogenetic stimulation of glutamatergic projection neurons in the BLA as rats learned object-context associations during a well-studied hippocampus-dependent memory task. Relative to a control condition, optogenetic BLA stimulation resulted in the accelerated acquisition of when stimulation was delivered following correct choices but not when it was delivered during the intertrial interval. These results extend prior examples of amygdala-mediated memory enhancement to a canonical example of hippocampus-dependent memory and provide an opportunity for future dissection of amygdalar modulation of object-context associative memory. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Several studies have shown that direct brain stimulation can enhance memory in humans and animal models. Investigating the neurophysiological changes induced by brain stimulation is an important step towards understanding the neural processes underlying memory function. Furthermore, it paves the way for developing more efficient neuromodulation approaches for memory enhancement. In this study, we utilized a combination of unsupervised and supervised machine learning approaches to investigate how amygdala stimulation modulated hippocampal network activities during the encoding phase. Using a sliding window in time, we estimated the hippocampal dynamic functional network connectivity (dFNC) after stimulation and during sham trials, based on the covariance of local field potential recordings in 4 subregions of the hippocampus. We extracted different network states by combining the dFNC samples from 5 subjects and applying k-means clustering. Next, we used the between-state transition numbers as the latent features to classify between amygdala stimulation and sham trials across all subjects. By training a logistic regression model, we could differentiate stimulated from sham trials with 67% accuracy across all subjects. Using elastic net regularization as a feature selection method, we identified specific patterns of hippocampal network state transition in response to amygdala stimulation. These results offer a new approach to better understanding of the causal relationship between hippocampal network dynamics and memory-enhancing amygdala stimulation.

The amygdala can modulate declarative memory. For example, previous research in rats and humans showed that brief electrical stimulation to the basolateral complex of the amygdala (BLA) prioritized specific objects to be consolidated into long term memory in the absence of emotional stimuli and without awareness of stimulation. The capacity of the BLA to influence memory depends on its substantial projections to many other brain regions, including the hippocampus. Nevertheless, how activation of the BLA influences ongoing neuronal activity in other regions is poorly understood. The current study used optogenetic stimulation of putative glutamatergic neurons in the BLA of freely exploring rats to determine whether brief activation of the BLA could increase in the hippocampus gamma oscillations for which the amplitude was modulated by the phase of theta oscillations, an oscillatory state previously reported to correlate with good memory. BLA neurons were stimulated in 1-s bouts with pulse frequencies that included the theta range (8 Hz), the gamma range (50 Hz), or a combination of both ranges (eight 50-Hz bursts). Local field potentials were recorded in the BLA and in the pyramidal layer of CA1 in the intermediate hippocampus. A key question was whether BLA stimulation at either theta or gamma frequencies could combine with ongoing hippocampal oscillations to result in theta-modulated gamma or whether BLA stimulation that included both theta and gamma frequencies would be necessary to increase theta-gamma comodulation in the hippocampus. All stimulation conditions elicited robust responses in BLA and CA1, but theta-modulated gamma oscillations increased in CA1 only when BLA stimulation included both theta and gamma frequencies. Longer bouts (5-s) of BLA stimulation resulted in hippocampal activity that evolved away from the initial oscillatory states and toward those characterized more by prominent low-frequency oscillations. The current results indicated that one mechanism by which the amygdala might influence declarative memory is by eliciting neuronal oscillatory states in the hippocampus that benefit memory.

Background: Awake neurosurgery requires patients to converse and respond to visual or verbal prompts to identify and protect brain tissue supporting essential functions such as language, primary sensory modalities, and motor function. These procedures can be poorly tolerated because of patient anxiety, yet acute anxiolytic medications typically cause sedation and impair cortical function., Methods: In this study, direct electrical stimulation of the left dorsal anterior cingulum bundle was discovered to reliably evoke positive affect and anxiolysis without sedation in a patient with epilepsy undergoing research testing during standard inpatient intracranial electrode monitoring. These effects were quantified using subjective and objective behavioral measures, and stimulation was found to evoke robust changes in local and distant neural activity., Results: The index patient ultimately required an awake craniotomy procedure to confirm safe resection margins in the treatment of her epilepsy. During the procedure, cingulum bundle stimulation enhanced positive affect and reduced the patient's anxiety to the point that intravenous anesthetic/anxiolytic medications were discontinued and cognitive testing was completed. Behavioral responses were subsequently replicated in 2 patients with anatomically similar electrode placements localized to an approximately 1-cm span along the anterior dorsal cingulum bundle above genu of the corpus callosum., Conclusions: The current study demonstrates a robust anxiolytic response to cingulum bundle stimulation in 3 patients with epilepsy., Trial Registration: The current study was not affiliated with any formal clinical trial., Funding: This project was supported by the American Foundation for Suicide Prevention and the NIH.

Alzheimer's disease (AD) is a neurodegenerative disease that disproportionately impacts memory and the hippocampus. However, it is unclear how AD pathology influences the activity of surviving neurons in the hippocampus to contribute to the memory symptoms in AD. One well-understood connection between spatial memory and neuronal activity in healthy brains is the activity of place cells, neurons in the hippocampus that fire preferentially in a specific location of a given environment (the place field of the place cell). In the present study, place cells were recorded from the hippocampus in a recently-developed rat model of AD (Tg-F344 AD) at an age (12-20 months) at which the AD rats showed marked spatial memory deficits. Place cells in the CA2 and CA3 pyramidal regions of the hippocampus in AD rats showed sharply reduced spatial fidelity relative to wild-type (WT) rats. In contrast, spiking activity of place cells recorded in region CA1 in AD rats showed good spatial fidelity that was similar to CA1 place cells in WT rats. Oral administration of the M 1 muscarinic acetylcholine receptor agonist VU0364572 impacted place cell firing rates in CA1 and CA2/3 hippocampal regions, but did not improve the spatial fidelity of CA2/3 hippocampal place cells in AD rats. The results indicated that, to the extent the spatial memory impairment in AD rats was attributable to hippocampal dysfunction, the memory impairment was more attributable to dysfunction in hippocampal regions CA2 and CA3 rather than CA1., (© 2018 Wiley Periodicals, Inc.)

Retrieval of autobiographical memories entails periods of search, access, and elaboration. Women's reports of their memories feature more detail and emotional content relative to men's. A key question is how these gender differences relate to unfolding changes in cortical activity during retrieval. We recorded EEG activity from 32 scalp electrodes as women and men were cued to retrieve positive, negative, and neutral autobiographical memories. Alpha (9-12Hz) oscillations were prominent at all EEG channels. Alpha coherence between channels was calculated as a measure of ms-level cortical synchrony. Across participants and memory types, a frontal cluster showed pronounced decreases in coherence with other channels during the first second of autobiographical retrieval. In the following second, a left parietal-centered cluster showed increased coherence with other channels. This effect strengthened and spread in the third second of retrieval, perhaps reflecting trace elaboration and/or evaluation of the memory. Although women and men gave similar subjective ratings of their memories, the second-by-second pattern of alpha coherence during autobiographical retrieval differed by gender and memory type. Specifically, women sustained the increased pattern of left-parietal coherence throughout the trial, whereas for men, alpha coherence in this cluster returned to baseline by second two for neutral memories and by second three for emotional memories. Examination of the temporal dynamics of cortical oscillations provides novel insight into autobiographical memory retrieval processes and to gendered retrieval in particular, suggesting that women may persist with elaboration and/or evaluation to a greater extent than men., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Emotional events are often remembered better than neutral events, a benefit that many studies have hypothesized to depend on the amygdala's interactions with memory systems. These studies have indicated that the amygdala can modulate memory-consolidation processes in other brain regions such as the hippocampus and perirhinal cortex. Indeed, rodent studies have demonstrated that direct activation of the amygdala can enhance memory consolidation even during nonemotional events. However, the premise that the amygdala causally enhances declarative memory has not been directly tested in humans. Here we tested whether brief electrical stimulation to the amygdala could enhance declarative memory for specific images of neutral objects without eliciting a subjective emotional response. Fourteen epilepsy patients undergoing monitoring of seizures via intracranial depth electrodes viewed a series of neutral object images, half of which were immediately followed by brief, low-amplitude electrical stimulation to the amygdala. Amygdala stimulation elicited no subjective emotional response but led to reliably improved memory compared with control images when patients were given a recognition-memory test the next day. Neuronal oscillations in the amygdala, hippocampus, and perirhinal cortex during this next-day memory test indicated that a neural correlate of the memory enhancement was increased theta and gamma oscillatory interactions between these regions, consistent with the idea that the amygdala prioritizes consolidation by engaging other memory regions. These results show that the amygdala can initiate endogenous memory prioritization processes in the absence of emotional input, addressing a fundamental question and opening a path to future therapies., Competing Interests: The authors declare no conflict of interest.

Neuronal oscillations in the rat hippocampus relate to both memory and locomotion, raising the question of how these cognitive and behavioral correlates interact to determine the oscillatory network state of this region. Here, rats freely locomoted while performing an object-location task designed to test hippocampus-dependent spatial associative memory. Rhythmic activity in theta, beta, slow gamma, and fast gamma frequency ranges were observed in both action potentials and local field potentials (LFPs) across four main hippocampal subregions. Several patterns of LFP oscillations corresponded to overt behavior (e.g., increased dentate gyrus-CA3 beta coherence during stationary moments and CA1-subiculum theta coherence during locomotion). In comparison, slow gamma (∼40 Hz) oscillations throughout the hippocampus related most specifically to object-location associative memory encoding rather than overt behavior. The results help to untangle how hippocampal oscillations relate to both memory and motion and single out slow gamma oscillations as a distinguishing correlate of spatial associative memory., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

The muscarinic M 1 acetylcholine receptor is a key target for drugs aimed at treating cognitive dysfunction, including the memory impairment in Alzheimer's disease. The overall question of the current study was to ask how systemic administration of the bitopic M 1 agonist VU0364572, the M 1 positive allosteric modulator BQCA, and the acetylcholinesterase inhibitor donepezil (current standard of care for Alzheimer's disease), would impact spatial memory-related hippocampal function in rats. Hippocampal pyramidal neuron spiking and local field potentials were recorded from regions CA1 and CA3 as rats freely foraged in a recording enclosure. To assess the relative stability versus flexibility of the rats' spatial representations, the walls of the recording enclosure were reshaped in 15-m intervals. As compared to the control condition, systemic administration of VU0364572 increased spatial correlations of CA1 and CA3 pyramidal neuron spiking across all enclosure shape comparisons, whereas BQCA and donepezil appeared to decrease these spatial correlations. Further, both VU0364572 and BQCA increased intrahippocampal synchrony as measured by CA3-CA1 field-field coherence in frequency ranges that tended to align with the prominence of those oscillations for the behavioral state (i.e., theta during locomotion and slow gamma during stationary moments). The results indicated that VU0364572 and BQCA influenced hippocampal function differently but in ways that might both be beneficial for treating memory dysfunction.

The present review highlights results from recent studies that delivered brief electrical stimulation to the basolateral complex of the amygdala in rats to reveal its capacity to prioritize declarative memories on a moment-to-moment basis even after the moment has passed. The results indicate that this memory enhancement depends on the hippocampus and elicits intrahippocampal gamma synchrony that possibly corresponds with sharpened hippocampal spike-timing dependent plasticity. These recent findings are discussed in relation to past studies of emotional memory in rodents and humans.

Recent research in humans has used formal models of temporal context, broadly defined as a lingering representation of recent experience, to explain a wide array of recall and recognition memory phenomena. One difficulty in extending this work to studies of experimental animals has been the challenge of developing a task to test temporal context effects on performance in rodents. The current study presents results from a novel object recognition memory paradigm that was adapted from a task used in humans and demonstrates a temporal context repetition effect in rats. Specifically, the findings indicate that repeating the first two objects from a once-encountered sequence of three objects incidentally cues memory for the third object, even in its absence. These results reveal that temporal context influences item memory in rats similar to the manner in which it influences memory in humans and also highlight a new task for future studies of temporal context in experimental animals.

Activation of the amygdala either during emotional arousal or by direct stimulation is thought to enhance memory in part by modulating plasticity in the hippocampus. However, precisely how the amygdala influences hippocampal activity to improve memory remains unclear. In the present study, brief electrical stimulation delivered to the basolateral complex of the amygdala (BLA) following encounters with some novel objects led to better memory for those objects 1 day later. Stimulation also elicited field-field and spike-field CA3-CA1 synchrony in the hippocampus in the low gamma frequency range (30-55 Hz), a range previously associated with spike timing and good memory. In addition, the hippocampal spiking patterns observed during BLA stimulation reflected recent patterns of activity in the hippocampus. Thus, the results indicate that amygdala activation can prioritize memory consolidation of specific object encounters by coordinating the precise timing of CA1 membrane depolarization with incoming CA3 spikes to initiate long-lasting spike-timing dependent plasticity at putative synapses between recently active neurons., ((c) 2015 APA, all rights reserved).)

Neuronal oscillations and cross-frequency interactions in the rat hippocampus relate in important ways to memory processes and serve as a model for studying oscillatory activity in cognition more broadly. We report here that hippocampal synchrony (CA3-CA1 coherence) increased markedly in the low gamma range as rats were exploring novel objects, particularly those for which the rat subsequently showed good memory. The gamma synchrony varied across phases of the theta rhythm such that coherence was highest at the falling slope and trough of the theta wave. Further, the shape of the theta wave was more asymmetric and elongated at the falling slope during exploration of objects for which the rat subsequently showed good memory as compared with objects for which the rat subsequently showed poor memory. The results showed a strong association between event-related gamma synchrony in rat hippocampus and memory encoding for novel objects. In addition, a novel potential mechanism of cross-frequency interactions was observed whereby dynamic alterations in the shape of theta wave related to memory in correspondence with the strength of gamma synchrony. These findings add to our understanding of how theta and gamma oscillations interact in the hippocampus in the service of memory., (Copyright © 2013 Wiley Periodicals, Inc.)

Acetylcholine signaling through muscarinic receptors has been shown to benefit memory performance in some conditions, but pan-muscarinic activation also frequently leads to peripheral side effects. Drug therapies that selectively target M1 or M4 muscarinic receptors could potentially improve memory while minimizing side effects mediated by the other muscarinic receptor subtypes. The ability of three recently developed drugs that selectively activate M1 or M4 receptors to improve recognition memory was tested by giving Long-Evans rats subcutaneous injections of three different doses of the M1 agonist VU0364572, the M1 positive allosteric modulator BQCA or the M4 positive allosteric modulator VU0152100 before performing an object recognition memory task. VU0364572 at 0.1 mg/kg, BQCA at 1.0 mg/kg and VU0152100 at 3.0 and 30.0 mg/kg improved the memory performance of rats that performed poorly at baseline, yet the improvements in memory performance were the most statistically robust for VU0152100 at 3.0 mg/kg. The results suggested that selective M1 and M4 receptor activation each improved memory but that the likelihood of obtaining behavioral efficacy at a given dose might vary between subjects even in healthy groups depending on baseline performance. These results also highlighted the potential of drug therapies that selectively target M1 or M4 receptors to improve memory performance in individuals with impaired memory.

Emotional events are often remembered better than neutral events, a type of memory prioritization by affective salience that depends on the amygdala. Studies with rats have indicated that direct activation of the basolateral complex of the amygdala (BLA) can enhance memory for neutral events, and if the activation is brief and temporally targeted, can do so in a way that benefits memories for specific events. The essential targets of BLA activation in the case of event-specific memory enhancement were unknown, but the hippocampus was known to receive direct projections from the BLA and to support memory for events. In the present study, rats received counterbalanced infusions of either muscimol, a GABAA receptor agonist, or saline into the hippocampus prior to performing a novel object recognition memory task during which initial encounters with some of the objects were immediately followed by brief electrical stimulation to the BLA. When memory was tested 1day later in the saline condition, rats remembered these objects well but showed no memory for objects for which the initial encounter had not been followed by BLA stimulation. In contrast, no benefit to memory of BLA stimulation was observed in the muscimol condition. The results indicated that brief activation of the BLA can prioritize memories for events by enhancing memory for some object encounters but not others and that this benefit to memory depends on interactions between the amygdala and the hippocampus., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Wireless power, when coupled with miniaturized implantable electronics, has the potential to provide a solution to several challenges facing neuroscientists during basic and preclinical studies with freely behaving animals. The EnerCage system is one such solution as it allows for uninterrupted electrophysiology experiments over extended periods of time and vast experimental arenas, while eliminating the need for bulky battery payloads or tethering. It has a scalable array of overlapping planar spiral coils (PSCs) and three-axis magnetic sensors for focused wireless power transmission to devices on freely moving subjects. In this paper, we present the first fully functional EnerCage system, in which the number of PSC drivers and magnetic sensors was reduced to one-third of the number used in our previous design via multicoil coupling. The power transfer efficiency (PTE) has been improved to 5.6% at a 120 mm coupling distance and a 48.5 mm lateral misalignment (worst case) between the transmitter (Tx) array and receiver (Rx) coils. The new EnerCage system is equipped with an Ethernet backbone, further supporting its modular/scalable architecture, which, in turn, allows experimental arenas with arbitrary shapes and dimensions. A set of experiments on a freely behaving rat were conducted by continuously delivering 20 mW to the electronics in the animal headstage for more than one hour in a powered 3538 cm(2) experimental area.

A low-noise wideband receiver (Rx) is presented for a multichannel wireless implantable neural recording (WINeR) system that utilizes time-division multiplexing of pulse width modulated (PWM) samples. The WINeR-6 Rx consists of four parts: 1) RF front end; 2) signal conditioning; 3) analog output (AO); and 4) field-programmable gate array (FPGA) back end. The RF front end receives RF-modulated neural signals in the 403-490 MHz band with a wide bandwidth of 18 MHz. The frequency-shift keying (FSK) PWM demodulator in the FPGA is a time-to-digital converter with 304 ps resolution, which converts the analog pulse width information to 16-bit digital samples. Automated frequency tracking has been implemented in the Rx to lock onto the free-running voltage-controlled oscillator in the transmitter (Tx). Two antennas and two parallel RF paths are used to increase the wireless coverage area. BCI-2000 graphical user interface has been adopted and modified to acquire, visualize, and record the recovered neural signals in real time. The AO module picks three demultiplexed channels and converts them into analog signals for direct observation on an oscilloscope. One of these signals is further amplified to generate an audio output, offering users the ability to listen to ongoing neural activity. Bench-top testing of the Rx performance with a 32-channel WINeR-6 Tx showed that the input referred noise of the entire system at a Tx-Rx distance of 1.5 m was 4.58 μV rms with 8-bit resolution at 640 kSps. In an in vivo experiment, location-specific receptive fields of hippocampal place cells were mapped during a behavioral experiment in which a rat completed 40 laps in a large circular track. Results were compared against those acquired from the same animal and the same set of electrodes by a commercial hardwired recording system to validate the wirelessly recorded signals.

The basolateral complex of the amygdala (BLA) modulates memory for emotional events, and direct activation of the BLA following a learning session can enhance subsequent memory. Yet optimal enhancement of episodic memory during emotional events would likely require that BLA activation occur close in time to the event and to be brief enough to target specific memories if some events are to be remembered better than others. In the present study, rats were given a novel object recognition memory task in which initial encounters with some of the objects were immediately followed by brief electrical stimulation of the BLA, and these objects were remembered better one day later as compared to objects for which the initial encounter was not followed by stimulation. The results indicated that BLA stimulation can enhance memory for individual events, a necessary ability for the BLA to modulate episodic memory effectively.

This paper reports scientifically meaningful in vivo experiments using a 32-channel wireless neural recording system (WINeR). The WINeR system is divided into transmitter (Tx) and receiver (Rx) parts. On the Tx side, we had WINeR-6, a system-on-a-chip (SoC) that operated based on time division multiplexing (TDM) of pulse width modulated (PWM) samples. The chip was fabricated in a 0.5-µm CMOS process, occupying 4.9 × 3.3 mm(2) and consuming 15 mW from ±1.5V supplies. The Rx used two antennas with separate pathways to down-convert the RF signal from a large area. A time-to-digital converter (TDC) in an FPGA converted the PWM pulses into digitized samples. In order to further increase the wireless coverage area and eliminate blind spots within a large experimental arena, two receivers were synchronized. The WINeR system was used to record epileptic activities from a rat that was injected with tetanus toxin (TT) in the dorsal hippocampus. In a different in vivo experiment, place-specific firing fields of place cells, which are parts of the hippocampal-dependent memory, were mapped from a series of behavioral experiments from a rat running in a circular track. Results from the same animal were compared against a commercial hard-wired recording system to evaluate the quality of the wireless recordings.

Voltage-gated sodium channels (VGSCs) are responsible for the initiation and propagation of transient depolarizing currents and play a critical role in the electrical signaling between neurons. A null mutation in the VGSC gene SCN8A, which encodes the transmembrane protein Na(v)1.6, was identified previously in a human family. Heterozygous mutation carriers displayed a range of phenotypes, including ataxia, cognitive deficits, and emotional instability. A possible role for SCN8A was also proposed in studies examining the genetic basis of attempted suicide and bipolar disorder. In addition, mice with a Scn8a loss-of-function mutation (Scn8a(med-Tg/+)) show altered anxiety and depression-like phenotypes. Because psychiatric abnormalities are often associated with altered sleep and hormonal patterns, we evaluated heterozygous Scn8a(med-jo/+) mutants for alterations in sleep-wake architecture, diurnal corticosterone levels, and behavior. Compared with their wild-type littermates, Scn8a(med-jo/+) mutants experience more non-rapid eye movement (non-REM) sleep, a chronic impairment of REM sleep generation and quantity, and a lowered and flattened diurnal rhythm of corticosterone levels. No robust differences were observed between mutants and wild-type littermates in locomotor activity or in behavioral paradigms that evaluate anxiety or depression-like phenotypes; however, Scn8a(med-jo/+) mutants did show enhanced spatial memory. This study extends the spectrum of phenotypes associated with mutations in Scn8a and suggests a novel role for altered sodium channel function in human sleep disorders.

Phase-amplitude cross-frequency coupling (CFC) between theta (4-12 Hz) and gamma (30-100 Hz) oscillations occurs frequently in the hippocampus. However, it still remains unclear whether theta-gamma coupling has any functional significance. To address this issue, we studied CFC in local field potential oscillations recorded from the CA3 region of the dorsal hippocampus of rats as they learned to associate items with their spatial context. During the course of learning, the amplitude of the low gamma subband (30-60 Hz) became more strongly modulated by theta phase in CA3, and higher levels of theta-gamma modulation were maintained throughout overtraining sessions. Furthermore, the strength of theta-gamma coupling was directly correlated with the increase in performance accuracy during learning sessions. These findings suggest a role for hippocampal theta-gamma coupling in memory recall.

The hippocampus has been proposed to support a cognitive map, a mental representation of the spatial layout of an environment as well as the nonspatial items encountered in that environment. In the present study, we recorded simultaneously from 43 to 61 hippocampal pyramidal cells as rats performed an object recognition memory task in which novel and repeated objects were encountered in different locations on a circular track. Multivariate analyses of the neural data indicated that information about object identity was represented secondarily to the primary information dimension of object location. In addition, the neural data related to performance on the recognition memory task. The results suggested that objects were represented as points of interest on the hippocampal cognitive map and that this map was useful in remembering encounters with particular objects in specific locations.

Previous research indicates a critical role of the hippocampus in memory for events in the context in which they occur. However, studies to date have not provided compelling evidence that hippocampal neurons encode event-context conjunctions directly associated with this kind of learning. Here we report that, as animals learn different meanings for items in distinct contexts, individual hippocampal neurons develop responses to specific stimuli in the places where they have differential significance. Furthermore, this conjunctive coding evolves in the form of enhanced item-specific responses within a subset of the preexisting spatial representation. These findings support the view that conjunctive representations in the hippocampus underlie the acquisition of context-specific memories.

The hippocampus is thought to contribute to episodic memory in part by binding stimuli to their spatiotemporal context. The present study examined how hippocampal neuronal populations encode spatial and temporal context as rats performed a task in which they were required to remember the order of trial-unique sequences of odors. The results suggest that a gradual change in the pattern of hippocampal activity served as a temporal context for odor-sampling events and was important for successful subsequent memory of the order of those odors.

The hippocampal theta rhythm is a prominent oscillation in the field potential observed throughout the hippocampus as a rat investigates stimuli in the environment. A recent computational model [Hasselmo, M. E., Bodelon, C., & Wyble, B. P. (2002a). A proposed function for hippocampal theta rhythm: separate phases of encoding and retrieval enhance reversal of prior learning. Neural Computation, 14, 793-817. Neuromodulation, theta rhythm and rat spatial navigation. Neural Networks, 15, 689-707] suggested that the theta rhythm allows the hippocampal formation to alternate rapidly between conditions that promote memory encoding (strong synaptic input from entorhinal cortex to areas CA3 and CA1) and conditions that promote memory retrieval (strong synaptic input from CA3 to CA1). That model predicted that the preferred theta phase of CA1 spiking should differ for information being encoded versus information being retrieved. In the present study, the spiking activity of CA1 pyramidal cells was recorded while rats performed either an odor-cued delayed nonmatch-to-sample recognition memory test or an object recognition memory task based on the animal's spontaneous preference for novelty. In the test period of both tasks, the preferred theta phase exhibited by CA1 pyramidal cells differed between moments when the rat inspected repeated (match) and non-repeated (nonmatch) items. Also in the present study, additional modeling work extended the previous model to address the mean phase of CA1 spiking associated with stimuli inducing varying levels of retrieval relative to encoding, ranging from novel nonmatch stimuli with no retrieval to highly familiar repeated stimuli with extensive retrieval. The modeling results obtained here demonstrated that the experimentally observed phase differences are consistent with different levels of CA3 synaptic input to CA1 during recognition of repeated items.

The present review considers research on the hippocampus and related areas from humans and experimental animals and makes three main points. First, many of the anatomical details of the hippocampus and adjacent cortical areas in the parahippocampal region are conserved across mammals. Second, the functional role of these areas in declarative memory is also conserved across species. Third, an evolutionary approach will be key to understanding exactly how the local circuitry of the hippocampus and parahippocampal region supports declarative memory. To highlight the utility of this approach, a schematic model is described in which separate streams of spatial and nonspatial information converge on the hippocampus. By this view, a fundamental function of the mammalian hippocampus is to combine incoming information about spatial context from the postrhinal (parahippocampal in primates) cortex and medial entorhinal area with incoming information about nonspatial items from the perirhinal cortex and lateral entorhinal area. The underlying neurobiological computations that arise from local circuitry enable item-in-context memory and are proposed to be fundamental to many examples of declarative memory, including episodic memory in humans and spatial memory in experimental animals., (Copyright (c) 2006 Wiley-Liss, Inc.)

Early descriptions of the hippocampal formation emphasized the serial nature of its circuitry, a description that suggests even a focal lesion would break a chain of processing and leave the entire region inoperative. Nevertheless, R. P. Kesner, M. R. Hunsaker, and P. E. Gilbert (2005) show that rats with CA1 lesions, but not rats with CA3 lesions, were impaired on a task in which animals were required to make associations between an object and an odor that were separated by a brief (10-s) delay. The present commentary makes 2 points relevant to their findings. First, several lines of evidence suggest that CA1 can operate somewhat independently of CA3 in some instances. Second, it is unclear whether the delay interval acted directly (by requiring a memory for a timeline of events) or indirectly (by outlasting the associative abilities of areas other than CA1) in causing performance to depend on the integrity of CA1., ((c) 2005 APA)

There has been debate about whether differential delay eyeblink conditioning can be acquired without awareness of the stimulus contingencies. In 4 experiments, the authors reexamined this question. Older participants were tested with a tone and white noise (Experiment 1) or with 2 tones (Experiment 2). In addition, younger participants were tested with 2 tones (Experiment 3) or with 2 tones plus the parameters from an earlier study that had reported a relationship between conditioning and awareness (Experiment 4). Participants who were designated aware of the stimulus contingencies and participants who were designated unaware exhibited equivalent levels of differential eyeblink conditioning. Awareness of stimulus contingencies is not required for differential delay eyeblink conditioning when simple conditioned stimuli are used., (Copyright 2005 APA.)

In a recent study, rats with hippocampal lesions performed as well as did unoperated rats on an olfactory memory span task, performing approximately 80% correct even when the span length reached 24 odors. This finding seems potentially at odds with demonstrations that memory-impaired patients typically fail tasks in which large amounts of information must be retained. Accordingly, we have assessed recognition memory span performance for line drawings of objects, designs, and odors in amnesic patients with damage thought to be limited to the hippocampal region. The patients were impaired on all three tasks. We consider possible explanations for the difference between the findings for humans and rats, including the fact that olfactory function is particularly well-developed in rodents.

It has been unclear whether the hippocampus is uniquely important for episodic memory (memory for events that are specific to time and place) or whether the hippocampus is also important for learning and remembering facts (semantic memory). In two studies, we assessed the capacity for semantic memory in patients with bilateral damage thought to be restricted primarily to the hippocampal region who developed memory impairment at a known time. Since the onset of their memory impairment, the patients have acquired less factual knowledge than controls. The patients also exhibit temporally limited retrograde amnesia for factual information from the several years preceding the onset of memory impairment. Remote memory for factual knowledge (from 11-30 years before amnesia) is intact. The results show that the hippocampal region supports semantic memory as well as episodic memory and that its role in the acquisition and storage of semantic knowledge is time limited.

The capacity for declarative memory depends on the hippocampal region and adjacent cortex within the medial temporal lobe. One of the most widely studied examples of declarative memory is the capacity to recognize recently encountered material as familiar, but uncertainty remains about whether intact recognition memory depends on the hippocampal region itself and, if so, what the nature of the hippocampal contribution might be. Seven patients with bilateral damage thought to be limited primarily to the hippocampal region were impaired on three standard tests of recognition memory. In addition, the patients were impaired to a similar extent at Remembering and Knowing, measures of the two processes thought to support recognition performance: the ability to remember the learning episode (episodic recollection) and the capacity for judging items as familiar (familiarity).

Memory is composed of several different abilities that are supported by different brain systems. The distinction between declarative (conscious) and nondeclarative (non-conscious) memory has proved useful in understanding the nature of eyeblink classical conditioning - the best understood example of classical conditioning in vertebrates. In delay conditioning, the standard procedure, conditioning depends on the cerebellum and brainstem and is intact in amnesia. Trace conditioning, a variant of the standard procedure, depends additionally on the hippocampus and neocortex and is impaired in amnesia. Recent studies have sharpened the contrast between delay and trace conditioning by exploring the importance of awareness. We discuss these new findings in relation to the brain systems supporting eyeblink conditioning and suggest why awareness is important for trace conditioning but not for delay conditioning.