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

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

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

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

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

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

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

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

Early childhood is characterized by vast changes in behaviors supported by the hippocampus and an increased susceptibility of the hippocampus to environmental influences. Thus, it is an important time to investigate the development of the hippocampus. Existing research suggests subregions of the hippocampus (i.e., head, body, tail) have dissociable functions and that the relations between subregions

Hippocampal circuitry has been posited to be fundamental to positive symptoms in psychosis, but its contributions to other factors important for outcome remains unclear. We hypothesized that longitudinal changes in the hippocampal circuit and concomitant changes of intracortical microstructure are altered in first episode psychosis (FEP) patients and that such changes are associated with negative symptoms

Neuromodulatory regions that detect salience, such as amygdala and ventral tegmental area (VTA), have distinct effects on memory. Yet, questions remain about how these modulatory regions target subregions across the hippocampus and medial temporal lobe (MTL) cortex. Here, we sought to characterize how VTA and amygdala subregions (i.e., basolateral amygdala and central‐medial amygdala) interact with

The discovery of long‐term potentiation (LTP) provided the first, direct evidence for long‐lasting synaptic plasticity in the living brain. Consequently, LTP was proposed to serve as a mechanism for information storage among neurons, thus providing the basis for the behavioral and psychological phenomena of learning and long‐term memory formation. However, for several decades, the LTP‐memory hypothesis

The rodent hippocampus expresses a variety of neuronal network oscillations depending on the behavioral state of the animal. Locomotion and active exploration are accompanied by theta‐nested gamma oscillations while resting states and slow‐wave sleep are dominated by intermittent sharp wave‐ripple complexes. It is believed that gamma rhythms create a framework for efficient acquisition of information

Reduced inhibitory GABA function, so‐called neural disinhibition, has been implicated in cognitive disorders, including schizophrenia and age‐related cognitive decline. We previously showed in rats that hippocampal disinhibition by local microinfusion of the GABA‐A receptor antagonist picrotoxin disrupted memory and attention and enhanced hippocampal multi‐unit burst firing recorded around the infusion

The functional connectivity of the hippocampus with its primary cortical input, the entorhinal cortex, is organized topographically. In area CA1 of the hippocampus, this leads to different functional gradients along the proximodistal and septotemporal axes of spatial/sensory responsivity and spatial resolution respectively. CA1 ripples, a network phenomenon, allow us to test whether the hippocampal

Neurobiological changes that occur with aging include a reduction in function and volume of the hippocampus. These changes were associated with corresponding memory deficits in navigation tasks. However, navigation can involve different strategies that are dependent on the hippocampus and caudate nucleus. The proportion of people using hippocampus‐dependent spatial strategies decreases across the lifespan

Toll‐like receptor 4 (TLR4) is primarily responsible for initiating an immune response following pathogen recognition. However, TLR4 is also expressed on neural progenitor cells and has been reported to regulate hippocampal neurogenesis as young male TLR4 knockout mice show increases in cell proliferation and doublecortin positive cells. Whether these effects occur in both sexes and are sustained with

Autoimmune limbic encephalitis associated with antibodies to components of the voltage‐gated potassium channel complex (VGKCC‐Ab‐LE) often leads to focal hippocampal atrophy and persistent episodic memory impairment (Butler et al., 2014; Loane et al., 2019). In an interesting study of 7 VGKCC‐Ab‐LE patients with hippocampal damage, Lad, Mullally, Houston, Kelly, and Griffiths (2019) reported (a) impaired

The importance of the hippocampus in spatial learning is well established, but the precise relative contributions by the dorsal (septal) and ventral (temporal) subregions remain unresolved. One debate revolves around the extent to which the ventral hippocampus contributes to spatial navigation and learning. Here, separate small subtotal lesions of dorsal hippocampus or ventral hippocampus alone (destroying

Extensive computational modeling has focused on the hippocampal formation and associated cortical structures. This overview describes some of the factors that have motivated the strong focus on these structures, including major experimental findings and their impact on computational models. This overview provides a framework for describing the topics addressed by individual articles in this special

Nearby grid cells have been observed to express a remarkable degree of long-range order, which is often idealized as extending potentially to infinity. Yet their strict periodic firing and ensemble coherence are theoretically possible only in flat environments, much unlike the burrows which rodents usually live in. Are the symmetrical, coherent grid maps inferred in the lab relevant to chart their

The cellular and synaptic architecture of the rodent hippocampus has been described in thousands of peer-reviewed publications. However, no human- or machine-readable public catalog of synaptic electrophysiology data exists for this or any other neural system. Harnessing state-of-the-art information technology, we have developed a cloud-based toolset for identifying empirical evidence from the scientific

A theory and model of spatial coordinate transforms in the dorsal visual system through the parietal cortex that enable an interface via posterior cingulate and related retrosplenial cortex to allocentric spatial representations in the primate hippocampus is described. First, a new approach to coordinate transform learning in the brain is proposed, in which the traditional gain modulation is complemented

Phase precessing place cells encode spatial information on fine timescales via the timing of their spikes. This phase code has been extensively studied on linear tracks and for short runs in the open field. However, less is known about the phase code on unconstrained trajectories lasting tens of minutes, typical of open field foraging. In previous work (Monsalve-Mercado and Leibold, Physical Review

Grid cells in medial entorhinal cortex are notoriously variable in their responses, despite the striking hexagonal arrangement of their spatial firing fields. Indeed, when the animal moves through a firing field, grid cells often fire much more vigorously than predicted or do not fire at all. The source of this trial-to-trial variability is not completely understood. By analyzing grid-cell spike trains

Behavioral data shows that humans and animals have the capacity to learn rules of associations applied to specific examples, and generalize these rules to a broad variety of contexts. This article focuses on neural circuit mechanisms to perform a context-dependent association task that requires linking sensory stimuli to behavioral responses and generalizing to multiple other symmetrical contexts.

The hippocampal system contains neural populations that encode an animal's position and velocity as it navigates through space. Here, we show that such populations can embed two codes within their spike trains: a firing rate code ( R) conveyed by within-cell spike intervals, and a co-firing rate code ( R ˙ ) conveyed by between-cell spike intervals. These two codes behave as conjugates of one another

Grid cells provide a compelling example of a link between cellular activity and an abstract and difficult to define concept like space. Accordingly, a representational perspective on grid coding argues that neural grid coding underlies a fundamentally spatial metric. Recently, some theoretical proposals have suggested extending such a framework to nonspatial cognition as well, such as category learning

The hippocampus and dorsal striatum are both associated with temporal processing, but they are thought to play distinct roles. The hippocampus has been reported to contribute to storing temporal structure of events in memory, whereas the striatum contributes to temporal motor preparation and reward anticipation. Here, we asked whether the striatum cooperates with the hippocampus in processing the temporal

Though it has been known for over half a century that interference with the normal activity of septohippocampal neurons can abolish hippocampal theta rhythmicity, a definitive answer to the question of its function has remained elusive. To clarify the role of septal circuits and theta in location-specific activity of place cells and spatial behavior, three drugs were delivered to the medial septum

Primates use saccades to gather information about objects and their relative spatial arrangement, a process essential for visual perception and memory. It has been proposed that signals linked to saccades reset the phase of local field potential (LFP) oscillations in the hippocampus, providing a temporal window for visual signals to activate neurons in this region and influence memory formation. We

Researchers have taken a number of different approaches in their exploration of hippocampal function. One approach seeks to describe hippocampal function by probing the memory representations that the hippocampus supports. Another approach focuses on the role of the hippocampus in pattern separation and completion. Each of these approaches to understanding hippocampal function utilizes a distinct set

Hippocampal formation contains several classes of neurons thought to be involved in navigational processes, in particular place cells and grid cells. Place cells have been associated with a topological strategy for navigation, while grid cells have been suggested to support metric vector navigation. Grid cell-based vector navigation can support novel shortcuts across unexplored territory by providing

The dorsal and ventral regions of the rat longitudinal hippocampal axis are functionally distinct. That is, each region is associated with different behavioral tasks and disease susceptibilities due to underlying anatomical, and physiological differences. These differences are especially pronounced in area CA1, where significant differences in morphology, synaptic physiology, intrinsic excitability

In the adult mouse hippocampus, new neurons are produced by radial glia-like (RGL) neural stem cells in the subgranular zone, which extend their apical processes toward the molecular layer, and express the astrocyte marker glial fibrillary acidic protein, but not the astrocyte marker S100β. In rodent models of epilepsy, adult hippocampal neurogenesis was reported to be increased after acute and mild