Functional role of parallel circuits in the hippocampus

The hippocampal formation is one of the primary structures involved in episodic and spatial memory. Although the gross anatomy of hippocampus and its role in learning has been studied extensively, little is known about the microcircuits that underlie the computations involved and most of the studies also treat hippocampus as a single unit. However, the discovery of segregated parallel pathways of principal neurons in the hippocampus (Deguchi Y et al, 2011) across the three main sub regions (Dentate gyrus to CA3, CA3 to CA3, CA3 to CA1) implies that there could be differential processing of incoming information with little or complete absence of interference. In this thesis, the main question I address is what could be the role of these parallel circuits in the hippocampus and how does selective connectivity contribute to their role. In the first part I investigated the roles of principal neuron subpopulations in various hippocampal learning paradigms using activity and plasticity markers. The data from this part suggests that different principal neuron subpopulations are recruited by different types of learning. In the second part of the thesis, I explored how the selective connectivity contributes to the hippocampal memory formation by pharmacologically altering the selective connectivity during early stages of circuit development. The structural and behavioral evidence from the mice with altered connectivity clearly show that they have impaired hippocampal learning. In summary, the results in my thesis provide insight about the role of parallel circuits in hippocampus during different forms of learning and provides strong evidence that hippocampal circuits use biased connectivity to extract and process specific types of information.