CA2: A Highly Connected Intrahippocampal Relay

Although Lorente de No’ recognized the anatomical distinction of the hippocampal Cornu Ammonis (CA) 2 region, it had, until recently, been assigned no unique function. Its location between the key players of the circuit, CA3 and CA1, which along with the entorhinal cortex and dentate gyrus compose the classic trisynaptic circuit, further distracted research interest. However, the connectivity of CA2 pyramidal cells, together with unique patterns of gene expression, hints at a much larger contribution to hippocampal information processing than has been ascribed. Here we review recent advances that have identified new roles for CA2 in hippocampal centric processing, together with specialized functions in social memory and, potentially, as a broadcaster of novelty. These new data, together with CA2's role in disease, justify a closer look at how this small region exerts its influence and how it might best be exploited to understand and treat disease-related circuit dysfunctions.

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Does a Unique Type of CA3 Pyramidal Cell in Primates Bypass the Dentate Gate?

Journal of Neurophysiology ◽

10.1152/jn.01216.2004 ◽

2005 ◽

Vol 94 (1) ◽

pp. 896-900 ◽

Cited By ~ 2

Author(s):

Paul S. Buckmaster

Keyword(s):

Dentate Gyrus ◽

Entorhinal Cortex ◽

Synaptic Input ◽

Granule Cells ◽

Molecular Layer ◽

Pyramidal Cells ◽

Dendritic Morphology ◽

Dentate Granule Cells ◽

Excitatory Synaptic Input ◽

Ca3 Pyramidal Cells

The predominant excitatory synaptic input to the hippocampus arises from entorhinal cortical axons that synapse with dentate granule cells, which in turn synapse with CA3 pyramidal cells.Thus two highly excitable brain areas—the entorhinal cortex and the CA3 field—are separated by dentate granule cells, which have been proposed to function as a gate or filter. However, unlike rats, primates have “dentate” CA3 pyramidal cells with an apical dendrite that extends into the molecular layer of the dentate gyrus, where they could receive strong, monosynaptic, excitatory synaptic input from the entorhinal cortex. To test this possibility, the dentate gyrus molecular layer was stimulated while intracellular recordings were obtained from CA3 pyramidal cells in hippocampal slices from neurologically normal macaque monkeys. Stimulus intensity of the outer molecular layer of the dentate gyrus was standardized by the threshold intensity for evoking a dentate gyrus field potential population spike. Recorded proximal CA3 pyramidal cells were labeled with biocytin, processed with diaminobenzidine for visualization, and classified according to their dendritic morphology. In response to stimulation of the dentate gyrus molecular layer, action potential thresholds were similar in proximal CA3 pyramidal cells with different dendritic morphologies. These findings do not support the hypothesis that dentate CA3 pyramidal cells receive stronger synaptic input from the entorhinal cortex than do other proximal CA3 pyramidal cells.

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Dentate Gyrus and CA3 GABAergic Interneurons Bidirectionally Modulate Signatures of Internal and External Drive to CA1

10.1101/2021.01.04.425303 ◽

2021 ◽

Author(s):

Emily A. Aery Jones ◽

Antara Rao ◽

Misha Zilberter ◽

Biljana Djukic ◽

Anna K. Gillespie ◽

...

Keyword(s):

Information Processing ◽

Dentate Gyrus ◽

Entorhinal Cortex ◽

Local Field ◽

Opposite Effect ◽

Field Potential ◽

Gabaergic Neurons ◽

Gabaergic Interneurons ◽

Flow Of Information ◽

The Brain

SUMMARYSpecific classes of GABAergic neurons are thought to play specific roles in regulating information processing in the brain. In the hippocampus, two major classes – parvalbumin-expressing (PV+) and somatostatin-expressing (SST+) neurons – differentially regulate endogenous firing patterns and target different subcellular compartments of principal cells, but how these classes regulate the flow of information throughout the hippocampus is poorly understood. We hypothesized that PV+ and SST+ interneurons in the dentate gyrus (DG) and CA3 might differentially modulate CA3 patterns of output, thereby altering the influence of CA3 on CA1. We found that while suppressing either interneuron type increased DG and CA3 output, the effects on CA1 were very different. Suppressing PV+ interneurons increased local field potential signatures of coupling from CA3 to CA1 and decreased signatures of coupling from entorhinal cortex to CA1; suppressing SST+ interneurons had the opposite effect. Thus, DG and CA3 PV+ and SST+ interneurons bidirectionally modulate the flow of information through the hippocampal circuit.

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Reduced Cognitive Performance in Aged Rats Correlates with Increased Excitation/Inhibition Ratio in the Dentate Gyrus in Response to Lateral Entorhinal Input

10.1101/637439 ◽

2019 ◽

Author(s):

Trinh Tran ◽

Michelle Bridi ◽

Ming Teng Koh ◽

Michela Gallagher ◽

Alfredo Kirkwood

Keyword(s):

Dentate Gyrus ◽

Entorhinal Cortex ◽

Medial Temporal Lobe ◽

Granule Cells ◽

Memory Performance ◽

Pyramidal Cells ◽

Excitatory Input ◽

Inhibitory Interneurons ◽

Aged Rats ◽

Anatomical Studies

ABSTRACTAging often impairs cognitive functions associated with the medial temporal lobe (MTL). Anatomical studies identified the layer II pyramidal cells of the lateral entorhinal cortex (LEC) as one of the most vulnerable elements within the MTL. These cells provide a major excitatory input to the dentate gyrus hippocampal subfield by synapsing onto granule cells and onto local inhibitory interneurons, and a fraction of these contacts are lost in aged individuals with impaired learning. Using optogenetics we evaluated the functional status of the remaining inputs in an outbred rat model of aging that distinguishes between learning impaired and learning unimpaired individuals. We found that aging affects the pre- and postsynaptic strength of the LEC inputs onto granule cells. However, the magnitude these changes was similar in impaired and un-impaired rats. In contrast, the recruitment of inhibition by LEC activation was selectively reduced in the aged impaired subjects. These findings are consistent with the notion that the preservation of an adequate balance of excitation and inhibition is crucial for maintain proficient memory performance during aging.

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Synaptic Reorganization of the Perisomatic Inhibitory Network in Hippocampi of Temporal Lobe Epileptic Patients

BioMed Research International ◽

10.1155/2017/7154295 ◽

2017 ◽

Vol 2017 ◽

pp. 1-13 ◽

Cited By ~ 6

Author(s):

Lucia Wittner ◽

Zsófia Maglóczky

Keyword(s):

Dentate Gyrus ◽

Temporal Lobe ◽

Pyramidal Cells ◽

Epileptic Seizures ◽

Epileptic Activity ◽

Principal Cell ◽

Interictal Spikes ◽

Epileptic Patients ◽

Cornu Ammonis ◽

Inhibitory Signaling

GABAergic inhibition and particularly perisomatic inhibition play a crucial role in controlling the firing properties of large principal cell populations. Furthermore, GABAergic network is a key element in the therapy attempting to reduce epileptic activity. Here, we present a review showing the synaptic changes of perisomatic inhibitory neuronal subtypes in the hippocampus of temporal lobe epileptic patients, including parvalbumin- (PV-) containing and cannabinoid Type 1 (CB1) receptor-expressing (and mainly cholecystokinin-positive) perisomatic inhibitory cells, known to control hippocampal synchronies. We have examined the synaptic input of principal cells in the dentate gyrus and Cornu Ammonis region in human control and epileptic hippocampi. Perisomatic inhibitory terminals establishing symmetric synapses were found to be sprouted in the dentate gyrus. Preservation of perisomatic input was found in the Cornu Ammonis 1 and Cornu Ammonis 2 regions, as long as pyramidal cells are present. Higher density of CB1-immunostained terminals was found in the epileptic hippocampus of sclerotic patients, especially in the dentate gyrus. We concluded that both types of (PV- and GABAergic CB1-containing) perisomatic inhibitory cells are mainly preserved or showed sprouting in epileptic samples. The enhanced perisomatic inhibitory signaling may increase principal cell synchronization and contribute to generation of epileptic seizures and interictal spikes.

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Control of impulsivity by Gi-protein signalling in layer-5 pyramidal neurons of the anterior cingulate cortex

Communications Biology ◽

10.1038/s42003-021-02188-w ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Bastiaan van der Veen ◽

Sampath K. T. Kapanaiah ◽

Kasyoka Kilonzo ◽

Peter Steele-Perkins ◽

Martin M. Jendryka ◽

...

Keyword(s):

Gene Expression ◽

Anterior Cingulate Cortex ◽

Expression Analysis ◽

Gene Expression Analysis ◽

Pyramidal Neurons ◽

Treatment Options ◽

Pyramidal Cells ◽

Cingulate Cortex ◽

Cell Types ◽

Anterior Cingulate

AbstractPathological impulsivity is a debilitating symptom of multiple psychiatric diseases with few effective treatment options. To identify druggable receptors with anti-impulsive action we developed a systematic target discovery approach combining behavioural chemogenetics and gene expression analysis. Spatially restricted inhibition of three subdivisions of the prefrontal cortex of mice revealed that the anterior cingulate cortex (ACC) regulates premature responding, a form of motor impulsivity. Probing three G-protein cascades with designer receptors, we found that the activation of Gi-signalling in layer-5 pyramidal cells (L5-PCs) of the ACC strongly, reproducibly, and selectively decreased challenge-induced impulsivity. Differential gene expression analysis across murine ACC cell-types and 402 GPCRs revealed that - among Gi-coupled receptor-encoding genes - Grm2 is the most selectively expressed in L5-PCs while alternative targets were scarce. Validating our approach, we confirmed that mGluR2 activation reduced premature responding. These results suggest Gi-coupled receptors in ACC L5-PCs as therapeutic targets for impulse control disorders.

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Homologous laminar organization of the mouse and human subiculum

Scientific Reports ◽

10.1038/s41598-021-81362-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Michael S. Bienkowski ◽

Farshid Sepehrband ◽

Nyoman D. Kurniawan ◽

Jim Stanis ◽

Laura Korobkova ◽

...

Keyword(s):

Gene Expression ◽

Hippocampal Formation ◽

Expression Patterns ◽

Pyramidal Cells ◽

Brain Structures ◽

Longitudinal Axis ◽

Brain Atlas ◽

Fiber Density ◽

Laminar Organization ◽

Hybridization Data

AbstractThe subiculum is the major output component of the hippocampal formation and one of the major brain structures most affected by Alzheimer’s disease. Our previous work revealed a hidden laminar architecture within the mouse subiculum. However, the rotation of the hippocampal longitudinal axis across species makes it unclear how the laminar organization is represented in human subiculum. Using in situ hybridization data from the Allen Human Brain Atlas, we demonstrate that the human subiculum also contains complementary laminar gene expression patterns similar to the mouse. In addition, we provide evidence that the molecular domain boundaries in human subiculum correspond to microstructural differences observed in high resolution MRI and fiber density imaging. Finally, we show both similarities and differences in the gene expression profile of subiculum pyramidal cells within homologous lamina. Overall, we present a new 3D model of the anatomical organization of human subiculum and its evolution from the mouse.

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