We investigated synaptic mechanisms in the hippocampus that could explain how loss of circadian timing leads to impairments in spatial and recognition memory. Experiments were performed in hippocampal slices from Siberian hamsters (Phodopus sungorus) because, unlike mice and rats, their circadian rhythms are easily eliminated without modifications to their genome and without surgical manipulations

Adult‐born granule cells (abGCs) integrate into the hippocampus and form connections with dentate gyrus parvalbumin‐positive (PV+) interneurons, a circuit important for modulating plasticity. Many of these interneurons are surrounded by perineuronal nets (PNNs), extracellular matrix structures known to participate in plasticity. We compared abGC projections to PV+ interneurons with negative‐to‐low

Episodic memory depends on the computational process of pattern separation in order to establish distinct memory representations of similar episodes. Studies of pattern separation in humans rely on mnemonic discrimination tasks, which have been shown to tax hippocampal‐dependent pattern separation. Although previous neuroimaging research has focused on hippocampal processing, little is known about

The hippocampus and parahippocampal region are essential for representing episodic memories involving various spatial locations and objects, and for using those memories for future adaptive behavior. The “dual‐stream model” was initially formulated based on anatomical characteristics of the medial temporal lobe, dividing the parahippocampal region into two streams that separately process and relay

Long‐term potentiation (LTP) is a synaptic plasticity mechanism critical to long‐term memory. LTP induced in vivo is characterized by altered transcriptional activity, including a period of upregulation of gene expression which is followed by a later dominant downregulation. This temporal shift to downregulated gene expression is predicted to be partly mediated by epigenetic inhibitors of gene expression

Intrauterine growth restriction (IUGR) is associated with hippocampal alterations that can increase the risk of short‐term memory impairments later in life. Despite the role of hippocampal neurogenesis in learning and memory, research into the long‐lasting impact of IUGR on these processes is limited. We aimed to determine the effects of IUGR on neuronal proliferation, differentiation and morphology

Structural integrity of the human hippocampus is widely acknowledged to be necessary for the successful encoding and retrieval of autobiographical memories. However, evidence for an association between hippocampal volume and the ability to recall such memories in healthy individuals is mixed. Here we examined this issue further by combining two approaches. First, we focused on the anatomically distinct

Hippocampal volume is a marker of brain health and is reduced with aging and neurological disease. Exercise may be effective at increasing and preserving hippocampal volume, potentially serving as a treatment for conditions associated with hippocampal atrophy (e.g., dementia). This meta‐analysis aimed to identify whether exercise training has a positive effect on hippocampal volume and how population

Maximal aerobic capacity (MAC) has been associated with preserved neural tissue or brain maintenance (BM) in healthy older adults, including the hippocampus. Amnestic mild cognitive impairment (aMCI) is considered a prodromal stage of Alzheimer's disease. While aMCI is characterized by hippocampal deterioration, the MAC‐hippocampal relationship in these patients is not well understood. In contrast

A number of studies have reported the involvement of the ventral hippocampus (vHip) and the lateral septum (LS) in negative emotional responses. Besides these well‐documented functions, they are also thought to control feeding behavior. In particular, optogenetic and pharmacogenetic interventions to LS‐projecting vHip neurons have demonstrated that the vHip→LS neural circuit exerts an inhibition on

Dynamic signaling between the endocrine system (ES) and the nervous system (NS) is essential for brain and body homeostasis. In particular, reciprocal interaction occurs during pregnancy and motherhood that may involve changes in some brain plasticity processes. Prolactin (PRL), a hormone with pleiotropic effects on the NS, promotes maternal behavior and has been linked to modifications in brain circuits

We examined the role of the avian hippocampus and area parahippocampalis in serial‐order behavior and a variety of other tasks known to be sensitive to hippocampal damage in mammals. Damage to the hippocampus and area parahippocampalis caused impairments in autoshaping and performance on an analogue of a radial‐arm maze task, but had no effect on acquisition of 2‐item, 3‐item, and 4‐item serial‐order

Hippocampal theta oscillations have been implicated in spatial memory function in both rodents and humans. What is less clear is how hippocampal theta interacts with higher frequency oscillations to support long‐term memory. Here we asked 10 presurgical epilepsy patients undergoing intracranial EEG recording to perform a long‐term spatial memory task in desktop virtual reality and found that increased

Past studies find that chronic stress alters inhibitory, GABAergic circuitry of neurons in distinct hippocampal subregions. Less clear is whether these effects persist weeks after chronic stress ends, and whether these effects involve changes in the total number of hippocampal GABAergic neurons or modulates the function of specific GABAergic subtypes. A transgenic mouse line (VGAT:Cre Ai9) containing

High‐level cognitive abilities such as navigation and spatial memory are thought to rely on the activity of grid cells in the medial entorhinal cortex (MEC), which encode the animal's position in space with periodic triangular patterns. Yet the neural mechanisms that underlie grid‐cell activity are still unknown. Recent in vitro and in vivo experiments indicate that grid cells are embedded in highly

Retracted: Harvey, Eric; Blurton‐Jones, Matthew; Kennedy, Pamela J., Hippocampal BDNF regulates a shift from flexible, goal‐directed to habit memory system function following cocaine abstinence, Hippocampus 29 (11), (https://onlinelibrary.wiley.com/doi/full/10./hipo.23127). The above article, published online on June 17, 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement

Extensive computational modeling has focused on the hippocampal formation and related cortical structures. This introduction describes the topics addressed by individual articles in part two of this special issue of the journal Hippocampus on the topic of computational models of the hippocampus and related structures.

Adaptive memory requires the organism to form associations that bridge between events separated in time. Many studies show interactions between hippocampus (HPC) and prefrontal cortex (PFC) during formation of such associations. We analyze neural recording from monkey HPC and PFC during a memory task that requires the monkey to associate stimuli separated by about a second in time. After the first

Hippocampal sharp‐wave ripples (SWRs) support the reactivation of memory representations, relaying information to neocortex during “offline” and sleep‐dependent memory consolidation. While blockade of NMDA receptors (NMDAR) is known to affect both learning and subsequent consolidation, the specific contributions of NMDAR activation to SWR‐associated activity remain unclear. Here, we combine biophysical

Evidence of differential connectivity and activity patterns across the long‐axis of the hippocampus has led to many hypotheses about functional specialization of the anterior and posterior hippocampus, including a hypothesis linking the anterior hippocampus to memory encoding and the posterior hippocampus to memory retrieval. The hippocampal encoding/retrieval and network (HERNET) model of memory predicts

Childhood obesity is associated with negative physiological and cognitive health outcomes. The hippocampus is a diverse subcortical structure involved in learned feeding behaviors and energy regulation, and research has shown that the hippocampus is vulnerable to the effects of excess adiposity. Previous studies have demonstrated reduced hippocampal volume in overweight and obese children; however

Theta oscillations in the hippocampus have many behavioral correlates, with the magnitude and vigor of ongoing movement being the most salient. Many consider correlates of locomotion with hippocampal theta to be a confound in delineating theta contributions to cognitive processes. Theory and empirical experiments suggest theta‐movement relationships are important if spatial navigation is to support

The hippocampus carries out multiple functions: spatial cognition dorsally (DH) and regulation of emotionality‐driven behavior ventrally (VH). Previously, we showed that dendrites of DH and VH pyramidal neurons of female rats are still developing robustly during adolescence and are altered by the experience of food restriction and voluntary exercise on a wheel. We tested whether such anatomical changes

Obesity is a chronic condition associated with adverse memory and emotional outcomes in humans and animal models. We have recently demonstrated that post‐weaning (i.e., periadolescent) high‐fat diet (HFD)‐induced obesity has opposite effect on hippocampal and amygdala‐dependent memory in rodents: while HFD consumption impairs spatial and relational memory, it enhances cue‐dependent emotional memory

Traumatic brain injury (TBI) is associated with epileptiform activity in the hippocampus; however, the underlying mechanisms have not been fully determined. The goal was to understand what changes take place in intrinsic neuronal physiology in the hippocampus after blunt force trauma to the cortex. In this context, hyperpolarization‐activated cation current (Ih) currents may have a critical role in

The population of hippocampal neurons actively coding space continually changes across days as mice repeatedly perform tasks. Many hippocampal place cells become inactive while other previously silent neurons become active, challenging the idea that stable behaviors and memory representations are supported by stable patterns of neural activity. Active cell replacement may disambiguate unique episodes

Deliberation is thought to involve the internal simulation of the outcomes of candidate actions, the valuation of those outcomes, and the selection of the actions with the highest expected value. While it is known that deliberation involves prefrontal cortical areas, specifically the dorsomedial prefrontal cortex (dmPFC), as well as the hippocampus (HPC) and other brain regions, how these areas process

A functional gradient has been proposed across the medial temporal lobes (MTL) such that the anterior MTL is thought to support processing of individual items (e.g., item memory and complex object perception), whereas the posterior MTL is thought to support item‐context retrieval (e.g., source memory). Whereas functional imaging studies have provided evidence supporting this anatomical organization

To make optimal use of previous experiences, important neural activity sequences must be prioritized during hippocampal replay. Integrating insights about the interplay between CA3 and CA2, we propose a conceptual framework that allows the two regions to control which sequences are reactivated. We suggest that neuromodulatory‐gated plasticity and mutual inhibition enable discrete assembly sequences

The midline thalamus bidirectionally connects the medial prefrontal cortex (mPFC) and hippocampus (HC) creating a unique cortico‐thalamo‐cortical circuit fundamental to memory and executive function. While the anatomical connectivity of midline thalamus has been thoroughly investigated, little is known about its cellular organization within each nucleus. Here we used immunohistological techniques to

Differentiating between similar memories is a crucial cognitive function that enables correct episodic memory formation. The ability to separate the components of memories into distinct representations is thought to rely on a computational process known as pattern separation, by which differences are amplified to disambiguate similar events. Although pattern separation has been localized to the dentate

Mesial temporal lobe epilepsy (MTLE) is a chronic neurological disorder characterized by the occurrence of seizures, and histopathological abnormalities in the mesial temporal lobe structures, mainly hippocampal sclerosis (HS). We used a multi‐omics approach to determine the profile of transcript and protein expression in the dorsal and ventral hippocampal dentate gyrus (DG) and Cornu Ammonis 3 (CA3)

Adult neurogenesis has been implicated in learning and memory of complex spatial environments. However, new neurons also play a role in nonmnemonic behavior, including the stress response and attention shifting. Many commonly used spatial tasks are very simple, and unsuitable for detecting neurogenesis effects, or are aversively motivated, making it difficult to dissociate effects on spatial learning

In rodents, gene‐expression, neuronal tuning, connectivity and neurogenesis studies have postulated that the dorsal, the intermediate and the ventral hippocampal formation (HF) are distinct entities. These findings are underpinned by behavioral studies showing a dissociable role of dorsal and ventral HF in learning, memory, stress and emotional processing. However, up to now, the molecular basis of

Replicas of an aspect of an experienced event can serve as effective reminders, yet little is known about the neural basis of such reminding effects. Here we examined the neural activity underlying the memory‐enhancing effect of reminders 1 week after encoding of naturalistic film clip events. We used fMRI to determine differences in network activity associated with recently reactivated memories relative

Space and time are both essential features of episodic memory, for which the hippocampus is critical (Howard & Eichenbaum, 2015). Spatial tasks have been used effectively to study the behavioral relevance of place cells. However, the behavioral paradigms utilized for the study of time cells have not used time duration as a variable that animals need to be aware of to solve the task. Therefore, the

The hippocampus is known to play a critical role in a variety of complex abilities, including visual‐spatial reasoning, social functioning, and math. Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by deficits in visual‐spatial reasoning that are accompanied by impairment in social function or mathematics, as well as motor or executive function skills. Despite the

Alcohol withdrawal directly impacts the brain's stress and memory systems, which may underlie individual susceptibility to persistent drug and alcohol‐seeking behaviors. Numerous studies demonstrate that forced alcohol abstinence, which may lead to withdrawal, can impair fear‐related memory processes in rodents such as extinction learning; however, the underlying neural circuits mediating these impairments

Place and grid cells in the hippocampal formation are commonly thought to support a unified and coherent cognitive map of space. This mapping mechanism faces a challenge when a navigator is placed in a familiar environment that has been deformed from its original shape. Under such circumstances, many transformations could plausibly serve to map a navigator's familiar cognitive map to the deformed space

Hippocampal circuit alterations that differentially affect hippocampal subfields are associated with age‐related memory decline. Additionally, functional organization along the longitudinal axis of the hippocampus has revealed distinctions between anterior and posterior (A‐P) connectivity. Here, we examined the functional connectivity (FC) differences between young and older adults at high‐resolution

Analysis of long‐term potentiation (LTP) provides a powerful window into cellular mechanisms of learning and memory. Prior work shows late LTP (L‐LTP), lasting >3 hr, occurs abruptly at postnatal day 12 (P12) in the stratum radiatum of rat hippocampal area CA1. The goal here was to determine the developmental profile of synaptic plasticity leading to L‐LTP in the mouse hippocampus. Two mouse strains

Individuals can use diverse behavioral strategies to navigate their environment including hippocampal‐dependent place strategies reliant upon cognitive maps and striatal‐dependent response strategies reliant upon egocentric body turns. The existence of multiple memory systems appears to facilitate successful navigation across a wide range of environmental and physiological conditions. The mechanisms

Although the function of the hippocampus and adjacent medial temporal lobe (MTL) areas in forming associations is generally recognized, how MTL contributes to form creative associations that could result in novel and appropriate functions or meanings remains unclear. In this study, we compared highly creative combinations (HCCs) of two objects (e.g., that of “lifejacket” and “distress signal device”)

The timing between synaptic inputs has been proposed to play a role in the induction of plastic changes that enable neural circuits to store information. In the case of spike timing‐dependent plasticity (STDP), this relates to the interval between a synaptic input and a postsynaptic spike, thus providing a conceptual link to the Hebb learning rule. Experiments have documented STDP in many synapses

Hippocampal theta oscillations show prominent changes in frequency and amplitude depending on behavioral state or cognitive demands. How these dynamic changes in theta oscillations contribute to the spatial and temporal organization of hippocampal cells, and ultimately behavior, remain unclear. We used low‐theta frequency optogenetic stimulation to pace coordination of cellular and network activity

Neur1 and Neur2, mouse homologs of the Drosophila neur gene, consist of two neuralized homology repeat domains and a RING domain. Both Neur1 and Neur2 are expressed in the whole adult brain and encode E3 ubiquitin ligases, which play a crucial role in the Notch signaling pathways. A previous study reported that overexpression of Neur1 enhances hippocampus‐dependent memory, whereas the role of Neur2

We have previously shown that repetitive induction of long‐term potentiation (LTP) by glutamate (100 μM, 3 min, three times at 24‐hr intervals) provoked long‐lasting synaptic enhancement accompanied by synaptogenesis in rat hippocampal slice cultures, a phenomenon termed RISE (repetitive LTP‐induced synaptic enhancement). Here, we examined the role of Ca2+‐permeable (CP) AMPA receptors (AMPARs) in

The hippocampus has long been observed to encode a representation of an animal's position in space. Recent evidence suggests that the nature of this representation is somewhat predictive and can be modeled by learning a successor representation (SR) between distinct positions in an environment. However, this discretization of space is subjective making it difficult to formulate predictions about how

In this study, we explored the associations between the brain derived neurotrophic factor (BDNF) and the apolipoprotein E (APOE) polymorphisms and hippocampal subfields in 127 healthy participants (18–85 years). MRI datasets were collected on a 4.7 T system. Participants were administered the Wechsler Memory Scale to evaluate episodic memory function. Significant associations of both polymorphisms

Changes in the expression of HCN ion channels leading to changes in Ih function and neuronal excitability are considered to be possible mechanisms involved in epileptogenesis in kinds of human epilepsy. In previous animal studies of febrile seizures and temporal lobe epilepsy, changes in the expression of HCN1 and HCN2 channels at different time points and in different parts of the brain were not consistent

The hippocampus is a medial temporal lobe structure in the brain and is widely studied for its role in memory and learning, in particular, spacial memory and emotional responses. It was thought to be a homogenous structure but emerging evidence shows differentiation along the dorsoventral axis and even microdomains for functional and cellular markers. We have examined in two cell‐types of the hippocampal

The anatomy and physiology of monosynaptic connections in rodent hippocampal CA1 have been extensively studied in recent decades. Yet, the resulting knowledge remains disparate and difficult to reconcile. Here, we present a data‐driven approach to integrate the current state‐of‐the‐art knowledge on the synaptic anatomy and physiology of rodent hippocampal CA1, including axo‐dendritic innervation patterns