Dentate gyrus

The canonical model of the dentate gyrus (DG) of the hippocampus suggests the DG performs pattern separation, orthogonalizing similar input patterns [1, 2] aided by an approximate 5-fold expansion of the cell population relative to its entorhinal cortex inputs [3]. However, more recent experimental results challenge this standard model, suggesting the DG also supports the precise binding of objects and events to space and the integration of information across episodes [4]. Very recent studies attribute pattern separation and pattern integration to anatomically distinct parts of the DG, the sup

Memory-related computations must occur across various brain states, each characterized by distinct oscillatory patterns. Theta oscillations in the hippocampal CA1 region are prominent during movement and are thought to organize network computations during active exploration, such as the virtual spatial paths formed by the sequential activity of CA1 spatial-tuning neurons, or 'place cells,' known as theta sequences. However, it remains unclear how theta supports memory during periods of immobility, when CA1 theta oscillations dissipate. To address this, we recorded laminar neural activity using

…This talk will explore the role of the dentate gyrus (DG) anatomy in this context. The canonical DG model suggests it performs pattern separation. More recent experimental results challenge this standard model, suggesting DG function is more complex and also supports the precise binding of objects and events to space and the integration of information across episodes. Very recent studies attribute pattern separation and patte

Neuronal apoptosis is a mechanism used to clear the cells of oxidative stress or DNA damage and to refine the final number of neurons for a functional neuronal circuit. The tumour suppressor protein p53 is a key regulator of the cell cycle and serves as a checkpoint for eliminating neurons with high DNA damage, aberrant hyperproliferative signals or cellular stress. Meanwhile p53 is largely expressed in progenitors’ cells during development, in adult mice p53 expression is restricted to the neurogenic niches where it regulates cell proliferation and self-renewal. To investigate the functional

The endogenous circadian rhythm of organisms maintains fundamental physiological processes and behaviour by synchronising them to the external environment. Disturbance to this rhythm in our modern societies, caused by the use of artificial light in dark periods, electronic gadgets, shift work, and poor sleep hygiene negatively impacts physiological and cognitive health. Studies in rodent hippocampus show that neuronal membrane excitability shows a diurnal rhythm and disturbance to the circadian cycle impairs hippocampal plasticity and memory. However, it is not clear how acute circadian distur

…neurogenic niche is located in the dentate gyrus of the hippocampus, a brain area greatly involved in learning and memory. During the normal process of aging, hippocampal neurogenesis decreases substantially, and it is suggested that this decrease starts at the very first stages, if not immediately prior to, the development of mild cognitive impairment and/or dementia. Unfortunately, despite the increasin

Aging is characterized by impairments in decision-making, memory, and learning. Classical theories suggest that the cognitive decline may be caused by increased neural variability, reducing the signal-to-noise ratio of information processing in the central nervous system. To explicitly test this hypothesis, we investigate behavior and brain activity in young and old mice performing a visual decision-making task. Old animals show relatively worse performance (a shallower psychometric curve and slower reaction times). We then used extracellular neural recordings to quantify single-neuron variabi

Adult hippocampal neurogenesis (AHN) occurs in the subgranular zone (SGZ) of the dentate gyrus (DG) in mice and can be modulated by events such as hyperexcitability present in epilepsy. Evidence shows increased aberrant AHN in chronic severe epilepsy models; however, the impact of mild seizures remains to be explored. In this study, we administered intraperitoneally a low (5mg/kg) or a high dose (25 mg/kg) of kainic acid (KA) to Ascl1/Tom young mice (6-8 weeks) that allow us to target new neurons, to induce acute mild or acute severe seizures, respectively and evaluate differences in neurons b

…cells in the subventricular zone and dentate gyrus (DG). Since both regions comprise dopaminergic innervation and inputs from the nigrostriatal areas, it is plausible that dopaminergic system may exert some control over or under cytogenic brain regions.To investigate this, we used a transgenic rat (

Neuronal networks show synchronous activity or receive highly synchronous inputs during a variety of different behaviors. Deficits of synchronous activity are associated with impairment of cognition, whereas hypersynchrony can lead to epileptic seizures. Different network mechanisms for synchrony generation have been proposed and studied computationally and experimentally. One such mechanism (interneuron gamma generator, ING) relies solely on recurrent inhibitory interneuron connectivity. The number of inhibitory synapses must be sufficiently large, with the exact number depending on the other

…rats present neurogenic niches in the dentate gyrus of the hippocampus, which produce new granular neurons. Acomys cahirinusis a new mammalian regeneration model that features extraordinary regenerative abilities, including full section of injured spinal cord. Adult neurogenesis and how it potentially contributes to brain repair in A. cahirinus has not been addressed. Transgenic Cre recombinase-expr

The brainstem locus coeruleus (LC) is the sole source of noradrenaline in the neocortex, hippocampus and cerebellum. Noradrenaline (NA) is a neuromodulator involved in the regulation of excitability of brain networks. In this study, we investigated whether chemogenetic activation of the LC is able to induce hippocampal noradrenaline release and affects hippocampal excitability.Male Sprague Dawley rats (n=8) were injected with the viral vector CAV2-PRSx8-hM3Dq in the LC for expression of hM3Dq, which allows chemogenetic LC activation upon systemic injection with deschloroclozapine (DCZ). Rats w

The dentate gyrus (DG) plays a key role in the emergence of spatial and contextual map representation within the hippocampus during learning. Granule cells (GCs) of the DG receive their major spatial cortical input from the medial entorhinal cortex (MEC) via the perforant path. To determine whether inputs from the MEC (in particular layer II stellate cells) play a role in the capacity of the DG to differentiate between different environments, we aim to modulate their activity using DREADDs. Thanks to these pharmacogenetic tools, we can de- or hyper-polarize MEC-layer II stellate cells during e

During embryonic and postnatal development of the dentate gyrus (DG), neural stem cells (NSCs) proliferate, migrate and generate mature granule neurons. Unlike other brain regions, NSCs remain in the adult DG, mostly in a state of deep quiescence, with the ability to re-enter cell cycle and generate new neurons throughout life. The transitions back and forward from a proliferative state to a temporal shallow quiescence or primed state ensure the maintenance of stem cell population. However, it is unclear when and how adult NSCs acquire quiescence sub-states during development. Recently, we hav

Systemic lupus erythematosus (SLE) often impacts brain function, causing cognitive impairment and psychiatric disorders, referred to as neuropsychiatric SLE (NSLE). This research compares the neuronal morphology of SLE mouse models (NZB/W F1) and wild-type (WT) mice in the hippocampus, a brain area exhibiting significant effects from NSLE. Nissl-stained sections were processed via a deep learning method to outline individual cells, with and without Calcium Binding Proteins (CBPs). Morphological and density features were extracted at the cellular level, and cells were classified into distinct s

Early life stress (ELS) has profound and enduring effects on neurodevelopment and social functioning, contributing to the risk of neurodevelopmental disorders. The interleukin-1 receptor (IL-1R1) in the hippocampus plays a pivotal role in mediating the impact of stress on social behavior. However, the involvement of neuronal IL-1R1 (nIL-1R1) in ELS-induced social deficits remains poorly understood. This study aims to address this gap by utilizing a maternal separation (MS) paradigm and innovative cell-type-specific IL-1R1-expressing mouse lines to elucidate the role of nIL-1R1 in MS-induced lo

The Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS; OMIN#615722), is a rare neurodevelopmental disorder caused by mutations in the NR2F1 gene, a transcriptional regulator playing pleiotropic functions in brain development. Most NR2F1 pathological variants are deletions and/or mutations leading to haploinsufficiency or dominant negative effects. Although BBSOAS is characterized by a wide array of clinical features, intellectual disability (ID), visual impairment, and autism spectrum disorder (ASD) are predominant. Notably, NR2F1 is identified as a risk gene for ASD (SFARI database), sugge

…dendritic and spine remodelling of dentate gyrus granule cells after denervation. Our research aims to investigate the effect of the layer-selective denervation of the dentate gyrus on the proliferation and differentiation of neurons in the granule cell layer, as the mechanisms that drive the remodelling due to the loss of input are not yet understood. Therefore, in anaesthetised adult male C57Bl/6 mice, the transection of the perforant pathway was performed, resulting in the layer-specific denervation of dentate granule

Neurological disorders can be caused by genetic alterations in many genes; UBE3A is one such gene, as a mutation or deletion in the maternal copy of this gene has been shown to cause Angelman Syndrome (AS). AS is a developmental disorder that affects 1 in 15,000 live births, and is characterized by many symptoms, with seizures being highly penetrant and debilitating. Previous research on the pathological characterization of AS model mice showed an increased seizure susceptibility as well as abnormally high levels of perineuronal net (PNN) fluorescence. Our project aims to determine whether the

The medial (MPP) and lateral perforant path (LPP) inputs to the dentate gyrus (DG) comprise a prominent source of information for the hippocampus. Behavioral and anatomical studies have indicated that the MPP provides information about metric space and the LPP provides information about item identity to the hippocampus. This may influence how information is encoded in MPP and LPP inputs to the hippocampus.Here, we examined the frequency-dependency of synaptic plasticity in MPP-DG and LPP-DG synapses of the dorsal hippocampus of freely behaving adult male rats using patterned afferent stimulati

Schinzel-Giedion syndrome (SGS), a rare developmental disorder characterized by congenital anomalies, intellectual impairment and epilepsy, is attributed to de novo point mutations affecting SET binding protein 1 (SETBP1). These mutations lead to pathological protein accumulation, triggering a cascade of downstream effects, partially understood. Considering the significant neurological consequences of such germline mutations, it is reasonable to speculate that SETBP1 plays a crucial role during central nervous system development, although limited data are available. To dissect SGS epileptogene

The dentate gyrus (DG) serves as an information gateway to the hippocampal formation. It receives sensory information from entorhinal cortex via perforant path (PP) and can be subdivided into parts including a supra- and an infrapyramidal blade. Typically, synaptic plasticity within the DG has mostly been examined in the suprapyramidal blade, whereas little is known about the extent to which synaptic plasticity is expressed and maintained in the infrapyramidal blade.This study compared synaptic plasticity in both blades of the DG that was evoked by patterned electrophysiological stimulation of

…neuronal and glial plasticity in the dentate gyrus (DG) of the hip

Stress during adolescence is a known risk factor for neuropsychiatric disorders later in life, but how different factors alter the susceptibility to lasting cognitive or affective impairment is only partially understood. Here, we asked whether activin, a member of the TGF-β family, has a role in this process, the rationale being that activin affects the neural underpinnings of cognitive performance and affective behavior in the adult brain. We combined a mouse model of adolescent stress (corticosterone between postnatal days 30-45) with a transgenic mouse line expressing a dominant-negative mu