CA3

The hippocampal formation plays a key role in learning and memory, with CA3 thought to be the substrate of pattern completion [1]. However, its underlying computational and synaptic mechanisms are not yet understood. Here we analyze the mechanisms behind sequence replay through simulations of spiking neurons and a time-discrete model of moving membrane potential distributions. First, we simulated spiking networks of excitatory leaky integrate-and-fire cells forming a sequence of assemblies. The sequence contains both recurrent and feedforward connections (within and across assemblies, respect

…neurons, which receive inputs from the CA3 and entorhinal cortex (EC). No widely accepted network-based theory for place field formation exists, but many models offer mechanisms for place-field firing. One type of hypotheses proposes that it results from summated output of spatially tuned cells, like grid cells or boundary vector cells. Another suggests CA1 place fields are replicate of CA3 place fie

Mitochondrial calcium uniporter (MCU) is a protein that facilitates calcium ion influx into mitochondria. It is well established that MCU, through mitochondrial Ca2+ overload, may promote neuronal death in different neuropathological conditions, especially those involving excitotoxicity. Surprisingly, MCU distribution in hippocampus is inversely proportional to susceptibility of individual hippocampal subregions to death – the highest MCU expression is found in CA2, the lowest - in CA1 (the most and the least resistant regions, respectively). The aim of my study was therefore to assess cell ty

Hippocampal pyramidal cells (PCs) express spatially tuned activity (i.e., ‘place cells’ exhibiting ‘place fields’, PF) to support navigation. However, the cellular mechanisms of novel PF formation are elusive. Behavioral time scale synaptic plasticity (BTSP), recently described in mouse CA1PCs, is a putative mechanism of PF formation (Bittner et al., 2015). It starts with a silent PC exhibiting a large Ca2+ plateau in dendrites accompanied by somatic bursting, which initiates the emergence of tuning near the location of induction. Consequently, activity is strongest during formation and lower

…and humans suggests that subregion CA3 represents event-specific information, while subregion CA1 encodes more generalized information.The free-energy principle entails that neural networks with more generalized representations operate closer to criticality, where external

Memories are dynamic constructs whose properties change with time and experience. The biological mechanisms underpinning these dynamics remain elusive, particularly concerning how shifts in the composition of memory-encoding neuronal ensembles influence a memory properties’ evolution over time. Here we leveraged a developmental approach to target distinct subpopulations of principal neurons (“birthdated neurons”), and used calcium imaging, optogenetics, chemogenetics, in association with multiple hippocampus-dependent learning tasks to investigate their contribution to memory engrams over time

The hippocampal CA1 region continually receives a large array of intra and extra-hippocampal inputs. Local GABA-ergic interneurons in the strata radiatum and lacunosum-moleculare are thought to play a key role in structuring this incoming information. However, little is known about the in vivo electrophysiological characteristics of these superficial interneurons during behaviour. Here, we present ongoing work describing the firing properties of interneurons recorded in the stratum radiatum and lacunosum-moleculare in relation to pyramidal neuron activity and network oscillations in freely mov

The encoding or retrieval of a contextual fear memory recruits the activity of thousands of neurons across the mammalian brain. This ensemble of cells is often identified by immediate-early genes (IEGs), which are expressed following neuronal activity, but the extent to which the expression pattern of one IEG reflects another is unclear. Here, we examined the IEGs Arc/Arg3.1 and c-Fos across several brain regions during fear memory encoding or retrieval. Mice were administered a 3-shock contextual fear conditioning (CFC) paradigm and sacrificed 1h later (encoding), 1 h after context re-exposur

Spatial navigation impairments are among the earliest clinical manifestations of Alzheimer’s Disease (AD). Pyramidal cells of the hippocampus fire selectively when the animal is in a specific location in the environment, leading to the theory that the hippocampus plays a crucial role in forming a cognitive map of the environment. The phenomenon of “remapping”, where specific cells exhibit selective firing in distinct environments, is thought to support the formation of different memories. By performing in-vivo electrophysiological recordings in freely moving mice while they navigate through di

Temporal lobe epilepsy (TLE) is characterized by spontaneous recurrent seizures poorly controlled by antiseizure medications in over 30% of patients. The current study aims to investigate the most epileptogenic areas in a TLE animal model using high-density EEG.Sprague Dawley male rats were injected intraperitoneally with pilocarpine to induce the status epilepticus (SE) terminated 30 minutes later by ketamine/diazepam. Two weeks later animals were implanted with epidural electrodes in the frontal cortex and depth electrodes in several temporal areas. Video-EEG recordings (24h, >3 days/week

The oxidative stress and inflammation provoked by hypoxia can lead to damage to neurons in the hippocampus, a structure that plays a key role in learning and memory processes. Prevention of hypoxia-related damages may be achieved through different means: pharmacologically or behaviorally. Some plants have strong antioxidants properties, such as Guiera senegalensis (GS). Alternatively, performance of free-divers, without memory loss, suggests neuroprotective effects of extended training to apnea. We developed a rat model of hypoxia under voluntary apnea. Training consists of 3 to 4 weeks of hab

…rely on the dentate gyrus (DG) and the CA3 hippocampal areas. We previously showed that the DG conditional knock-out of Vangl2 – a core Planar Cell Polarity (PCP) gen

Novelty is an attribute of a stimulus that lacks a pre-existing representation and novelty detection involves a series of interrelated processes, each playing a unique role. Different medial temporal lobe structures including the hippocampus have been highly implicated to play a major role in novelty detection. In this project, we aim to understand how CA1 of the hippocampus encodes novelty and familiarity signals induced by unimodal and multimodal sensory stimuli and what are the processes that mediate the transition between novelty and familiarity. We plan to use a multisensory cue delivery

…particularly the dentate gyrus (DG)-CA3 mossy fiber system. These functions allow for the differentiation of similar memories as well as a generalization of a memory trace in response to incomplete sensory inputs. The salience of hippocampus-dependent contextual fear memories is controlled by local somatostatin (SST)-positive interneurons that regulate the excitability of DG granule cells. In the current study we investigate if SST-positive interneurons contribute to fear memory specificity

…hippocampal subregions, namely: CA1, CA3 and DG. While many studies have proved the anticonvulsant properties of the administration of anti-epileptic drugs, such as diazepam (DZP), a GABA-A receptor agonist, and carbamazepine (CBZ), a sodium channel blocker, their role in modulating the oscillatory patterns within these three regions remains unclear. Furthermore, the role of oscillatory dynamics in the pre-ictal period in predicting the emergence of a seizure events require further investigation. In our study,

…from both ipsi- and contralateral CA3 and CA2 regions. While synaptic plasticity at the intrahippocampal Schaffer collateral synapses has been extensively described, synaptic plasticity mechanisms at interhippocampal commissural fiber synapses are less well understood. In this project, we investigate cyclic adenosine monophosphate (cAMP)-dependent plasticity at commissural synapses in the CA1 region. We performed in vivo stereotactic injections of AAVs to express ChrimsonR unilaterally in CA3/CA2 glutamatergic neurons of one hippocamp

Understanding the neural mechanisms underlying memory formation and retrieval is fundamental to unraveling the pathophysiology of Alzheimer's disease (AD). Inhibitory interneurons have fundamental roles in shaping neural circuits and synaptic plasticity within the hippocampus, a brain region critical for memory encoding and consolidation. However, the specific contribution of inhibitory interneurons to the formation and maintenance of engrams, the neural representations of memories, remains poorly understood, particularly in the context of AD.To determine neurons participating in the engram fo

…provide a strong and sparse input onto CA3 that is thought to be important for learning and memory. These synapses have a low basal release probability and display various forms of plasticity: frequency facilitation, post-tetanic potentiation (PTP), and a cAMP-dependent presynaptic form of long-term potentiation (LTP).Synapsins are the most abundant neuronal phosphoproteins. Due to their phosphorylation-dependent association with synaptic vesicles they play an important role in synaptic transmission and plasticity.Differentl

Human brain function results from continuous activity flowing through specific cells, guided by specific synaptic arrangements. Therefore, determining the architecture and properties of functioning microcircuits is fundamental to understand the brain’s action. However, our current knowledge of human microcircuits is extremely limited, and relies heavily on assumptions from rodent research. Using tissue resected from 13 temporal lobe epilepsy patients, we perform multicellular patch-clamp based microcircuit analysis (n=80 recordings) to characterize synaptic connectivity in the human hippocampa

Introduction: Major depressive disorder (MDD) is a prevalent, complex condition with an unclear pathophysiology. Studies have shown structural and cellular changes in the hippocampus and reduced synaptic density in the prefrontal cortex of depressed individuals (Kang HJ et al. Nature Medicine 2012;18(9):1413-1417). Additionally, impaired mitochondrial function has been linked to susceptibility to mental health disorders.Objectives: This study aimed to examine synaptic and mitochondrial characteristics in post-mortem hippocampal tissues, specifically in individuals with MDD.Methods: The three s

…of spatial maps in proximal CA3 while rarely evoking neural activity. Stimulation of the same neuronal cohort on subsequent days recruits CA3 neurons with increased efficacy but fails to induce further r

…specifically in the DG and CA3. Using 3D reconstruction of confocal and SBFSEM acquisitions, we sho

Memories are believed to be stored in the strengthened synaptic connectivity between distributed networks of neurons after learning. This biophysical memory trace is often referred to as an engram, provisionally defined as the cells activated during learning, reactivated during memory retrieval, and causally linked to the expression of memory. Recent work exploring the activity of these ensembles in vivo demonstrates that after learning, c-Fos tagged populations consist of highly active, correlated ensembles of hippocampal neurons. The current model for engram formation predicts that during le

…manifold, or cognitive map, in CA3, with topological correspondence to space. Supporting this idea, continuous attractor neural networks (CANNs) show place cell-like tuning for spatial locations, and can be used to simulate plausible trajec