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bioRxiv · 10.1101/243022

Anterior thalamic excitation and feed-forward inhibition of presubicular neurons projecting to medial entorhinal cortex

Nassar, M.·Simonnet, J.·Huang, L.-W.·Mathon, B.·Cohen, I.·Bendels, M. H.·Beraneck, M.·Miles, R.·Fricker, D.
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Abstract

The presubiculum contains head direction cells that are crucial for spatial navigation. Here, we examined the connectivity and strengths of thalamic inputs to presubicular layer 3 neurons projecting to the medial entorhinal cortex in the mouse. We recorded pairs of projection neurons and interneurons while optogenetically stimulating afferent fibers from the anterior thalamic nuclei (ATN). Thalamic input differentially affects presubicular neurons: layer 3 pyramidal neurons and fast-spiking parvalbumin expressing (PV) interneurons are directly and monosynaptically activated, with depressing dynamics, while somatostatin (SST) expressing interneurons are indirectly excited, during repetitive ATN activity. This arrangement ensures that the thalamic excitation of layer 3 cells is often followed by disynaptic inhibition. Feed-forward inhibition is largely mediated by PV interneurons which have a high probability of connection to presubicular pyramidal cells. Our data point to a specific role of presubicular microcircuits in shaping thalamic head-direction signals transmitted to medial entorhinal cortex: Short-latency PV cell activation may enforce temporally precise head direction tuning during fast turns. However, depression at ATN-PV synapses during repeated activation tends to facilitate pyramidal cell firing when head direction is maintained. Operations performed in presubicular layer 3 circuits seem well-adapted for spatial fine-tuning of head direction signals sent to the medial entorhinal cortex.\n\nSIGNIFICANCE STATEMENTHow microcircuits participate in shaping neural inputs is crucial to understanding information processing in the brain. Here, we show how the presubiculum may process thalamic head directional information before transmitting it to the medial entorhinal cortex. Synaptic inputs from the anterior thalamic nuclei (ATN) excite layer 3 pyramidal cells (PC) and parvalbumin (PV) interneurons, which mediate disynaptic feed-forward inhibition. Somatostatin (SST) interneurons are excited indirectly. Presubicular circuits may switch between two regimes according to the angular velocity of head movements. During immobility, SST-PC interactions support maintained head directional firing with attractor-like dynamics. During rapid head turns, in contrast, PV mediated feed-forward inhibition acts to tune the head direction signal transmitted to medial entorhinal cortex.

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Nassar, M., Simonnet, J., Huang, L.-W., Mathon, B., Cohen, I., Bendels, M. H., Beraneck, M., Miles, R., Fricker, D.. 2018-01-04. Anterior thalamic excitation and feed-forward inhibition of presubicular neurons projecting to medial entorhinal cortex. https://doi.org/10.1101/243022

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