Sanchez Bellot, Candela; (2021) Investigating dichotomous projections from ventral hippocampus to prefrontal cortex. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

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.

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