Regional and subpopulation rules for plasticity in the adult mouse hippocampus

The aim of my thesis was to elucidate regional and subpopulation rules for structural plasticity in the adult mouse hippocampus, which can provide insights to information processing and memory formation within the hippocampal circuitry.
Previous studies have shown that dorsal, intermediate and ventral hippocampus have distinct coding and behavioural roles, consistent with the distinct afferent and efferent connectivities along the longitudinal (dorsoventral) axis of the hippocampus. In addition, evidence for distinct hippocampal regions has been provided in the form of discrete molecular domains of gene expression across the hippocampus. However, none of these studies has investigated the anatomy and connectivity at the level of individual identified neurons. Also, it still remains unknown whether structural plasticity upon experience and learning may differ along the dorsoventral axis of the hippocampus and across distinct mossy fibre subpopulations.
To address these questions, I mapped granule cell mossy fibre anatomy and connectivity throughout the hippocampus in three “sparse” Thy1 transgenic reporter mice (Lsi1, Lsi2 and Lsi3) that express membrane-targeted GFP in a subset of principal neurons. By combining behavioural and lesion experiments, as well as high-resolution confocal microscopy and gene expression analysis, I provide evidence that distinct regions of the hippocampus (dorsal, intermediate and ventral) and distinct subpopulations of granule cells exhibit different anatomy and connectivity under baseline conditions and upon learning. Using the growth of filopodial synapses that mediate feed-forward inhibition to the network in CA3 as a specific readout for learning, I show that the dorsal hippocampus encodes spatial information and is specifically recruited for spatial learning, while the ventral hippocampus encodes goal-oriented information and is specifically recruited for goal-oriented learning. Moreover, the results reveal objective distinctions at the circuit level between hippocampal-dependent memory and hippocampal-dependent learning. In addition, I provide evidence that distinct granule cell subpopulations respond in unique ways to experience and learning, suggesting that principal neuron subpopulations may have distinct functional roles in hippocampal-dependent learning and memory.