Learning-dependent modulation of inhibitory transmission in hippocampal CA1 area of adult mice

Abstract

Learning not only shapes the brain to form new memories but also affects future learning. Previous studies show that Pavlovian contextual fear conditioning (cFC) and environmental enrichment (EE) can inhibit or facilitate further learning via shifting parvalbumin (PV) interneurons network towards a high PV or low PV state in hippocampal neural circuit, respectively (Donato et al., 2013). The aim of my thesis study is to reveal the physiological relevance of learning-induced changes in PV interneuron network, and to investigate how these changes affect information processing of excitatory microcircuits. By combining transgenic mouse lines, electrophysiological and behavioural studies, we showed that cFC homogenized the firing behaviour of PV cells. More PV cells fired with no adaptation and higher firing rates; on the contrary, EE led to more diversified firing behaviour in PV cells: more cells fired with pronounced adaptation but within a wide range of firing frequency. Such learning-dependent intrinsic plasticity of PV cells further modified hippocampal CA1 inhibitory transmission. The results showed that the inhibitory transmission in CA1 area was enhanced upon cFC; similar to the modulation effect on intrinsic excitability, EE diversified its modulation on inhibitory transmission with different directions onto two sub-groups. Interestingly, when we examined the Lsi1 subpopulation of principal cells, cFC exerted equal modulation on PV cell-mediated inhibitory transmission in Lsi1 cells as in averaged group of pyramidal cells; while EE enhanced the total Inhibitory postsynaptic currents (IPSC) and slightly increased PV cell-mediated IPSCs, which is different from the averaged group of pyramidal cells in hippocampus. Overall, these results suggest that the behavioural experience can differentially modulate inhibitory transmission in hippocampal CA1 with a subpopulation specific manner. This neurophysiological knowledge will facilitate our understanding on the information processing in experience-modified neural circuits and how such modulation influence further learning. Future studies will be required to examine the molecular mechanism supporting these changes in inhibitory circuits upon learning.