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Authors & Affiliations
Genevieve Durocher, Paul Banks, Gareth Barker, Clair Booth, Clea Warburton, Zafar Bashir
Abstract
Associative recognition memory, such as finding your car in a carpark, requires the quick integration of familiarity, spatial location and temporal information that is vital for episodic experience. The medial prefrontal cortex (mPFC) is a key integration hub within the associative recognition memory circuit as it receives long range excitatory inputs from the nucleus reuniens (NRe) and intermediate hippocampus (iCA1), both pathways being critical for learning. Inhibitory interneurons play essential roles in spatial and working memory function by gating signal flow and sculpting microcircuit dynamics. However, the role mPFC interneurons have in associative recognition memory and its networks is unknown. Combining intersectional transsynaptic viral tracing, slice electrophysiology and in vivo wireless optogenetics, (PV, NDNF or SSTCre female and male mice (10 weeks old) we show that iCA1 and NRe projections have distinct laminar distribution within the prelimbic cortex, NRe predominately targets layer1 (L1) whereas iCA1 inputs are more uniformly distributed across prelimbic layers. Optogenetically activating iCA1 and NRe inputs ex vivo, differentially recruited PV interneurons compared to pyramidal neurons and had opposing short term plasticity at L1 NDNF interneurons. Wireless, in vivo optogenetic inhibition of NDNF and PV interneurons during an object in place associative recognition task is currently being undertaken and results analysed, with preliminary results showing high specificity of the inhibitory opsin and PV retrieval deficit. This work reveals that mPFC interneurons not only receive iCA1 and NRe inputs, but also differentially integrate these signals into mPFC microcircuits that could ultimately modulate distinct phases of associative recognition memory.