Investigating dichotomous projections from ventral hippocampus to prefrontal cortex

The ventral hippocampus is thought to be key in the production of exploratory, goal-directed and anxiety-like behaviour as well as in the expression and extinction of contextual fear. These roles are thought to be carried out via strong projections to structures such as the prefrontal cortex (PFC), where the hippocampus exerts tight excitatory and inhibitory control over downstream circuitry. The ventral hippocampal-prefrontal (vH-PFC) pathway is involved in the production of a range of behaviours including working memory, aversive learning and anxiety and its dys- function is linked to key aspects of several psychiatric disorders. How this pathway supports these functions is not fully understood and a mechanism for hippocampus- driven excitatory and inhibitory control of PFC, dependent on task demands, re- mains elusive. Moreover, how this hippocampal control over PFC and activity in the vH-PFC pathway is altered in disease is poorly understood. In this thesis, I found that the vH-PFC projection is composed of two distinct populations of neurons. These neurons form two layers, at the deep and superficial poles of the radial axis of the hippocampus. In line with previously established property gradients along the hippocampal radial axis, cells in the deep layer are more excitable and burst- firing, while cells in the superficial layer are regular-spiking. Additionally, cells in the two layers of the projection are differentially controlled by upstream structures. Superficial cells receive biased cortical input while deep cells preferentially receive input from subcortical structures. These two subpopulations have unique connectivity within downstream PFC, where differential recruitment of pyramidal cells and interneuron subclasses provide a mechanism for bidirectional control of PFC activity. Superficial layer cells preferentially recruit feedforward inhibition, while cells in the deep layer promote excitation. This long-range push-pull circuit provides a mechanism for regulation of exploratory behaviour in an approach-avoidance con- flict through tight hippocampal control of PFC, where activation of deep layer cells promotes avoidance and activation of superficial layer cells promotes exploration of the elevated plus maze

Prefrontal Interneurons: Populations, Pathways, and Plasticity Supporting Typical and Disordered Cognition in Rodent Models

Prefrontal cortex (PFC) inhibitory microcircuits regulate the gain and timing of pyramidal neuron firing, coordinate neural ensemble interactions, and gate local and long-range neural communication to support adaptive cognition and contextually tuned behavior. Accordingly, perturbations of PFC inhibitory microcircuits are thought to underlie dysregulated cognition and behavior in numerous psychiatric diseases and relevant animal models. This review, based on a Mini-Symposium presented at the 2022 Society for Neuroscience Meeting, highlights recent studies providing novel insights into: (1) discrete medial PFC (mPFC) interneuron populations in the mouse brain; (2) mPFC interneuron connections with, and regulation of, long-range mPFC afferents; and (3) circuit-specific plasticity of mPFC interneurons. The contributions of such populations, pathways, and plasticity to rodent cognition are discussed in the context of stress, reward, motivational conflict, and genetic mutations relevant to psychiatric disease

Aberrant survival of hippocampal Cajal-Retzius cells leads to memory deficits, gamma rhythmopathies and susceptibility to seizures in adult mice

International audienceAbstract Cajal-Retzius cells (CRs) are transient neurons, disappearing almost completely in the postnatal neocortex by programmed cell death (PCD), with a percentage surviving up to adulthood in the hippocampus. Here, we evaluate CR’s role in the establishment of adult neuronal and cognitive function using a mouse model preventing Bax-dependent PCD. CRs abnormal survival resulted in impairment of hippocampus-dependent memory, associated in vivo with attenuated theta oscillations and enhanced gamma activity in the dorsal CA1. At the cellular level, we observed transient changes in the number of NPY + cells and altered CA1 pyramidal cell spine density. At the synaptic level, these changes translated into enhanced inhibitory currents in hippocampal pyramidal cells. Finally, adult mutants displayed an increased susceptibility to lethal tonic-clonic seizures in a kainate model of epilepsy. Our data reveal that aberrant survival of a small proportion of postnatal hippocampal CRs results in cognitive deficits and epilepsy-prone phenotypes in adulthood