P3.28. PLASTICITY OF LAYER 1 INTERNEURONS OF THE MOUSE VISUAL CORTEX
Adrianna Nozownik1, Faezeh Rabbani1, Mai-An Nguyen1, Giuseppe Chiantia2, Yann Zerlaut1, Alberto Bacci1, Joana Lourençop1
1 ICM - Paris Brain Institute, Hôpital de la Salpêtrière, Paris, France
2 University of Turin, Department of Neuroscience, Turin, Italy
INTRODUCTION: The brain integrates internally generated information with external sensory inputs, and this is fundamental to adapting to dynamic environments. In primary sensory cortices, the most superficial Layer 1 (L1) plays a key role in integrating contextual (top-down) signals, which are modulated by local inhibitory GABAergic interneurons (INs). My research focuses on cannabinoid receptor type 1 (CB1), which we found to be expressed in neuron-derived neurotrophic factor (NDNF)-positive L1 INs of the mouse primary visual cortex (V1). CB1 modulates synaptic transmission through retrograde endocannabinoid (eCB) signaling, potentially serving as a mechanism to gate top-down signals to pyramidal neurons (PNs) during visual processing.
AIM(S): We hypothesize that CB1-mediated plasticity of dendritic inhibition from L1 INs gates contextual signals to PNs during sensory input. We aim to reveal the role of CB1-mediated plasticity of a specific V1 circuit in visual perception.
METHOD(S): Fluorescent in situ hybridization (FISH), Immuno-histochemistry (IHC), patch-clamp electrophysiology in acute brain slices, optogenetics, in vivo 2-photon (2p) Ca imaging
RESULTS: Using FISH, we found that ~70% of NDNF L1 INs express CB1. We confirmed CB1-mediated plasticity at L1 IN-L2/3 PN synapses using optogenetics and multiple patch-clamp electrophysiological recordings in acute cortical slices. Preliminary results from 2p-Ca imaging of L1 NDNF INs of head-fixed mice suggest that NDNF INs are more strongly recruited by non-visual spontaneous activity upon genetic knock-down of CB1 in L1 NDNF INs. We are presently analyzing the role of CB1 in L1 INs during the processing of visual stimulations.
CONCLUSIONS: Our findings indicate an unexpected source of activity-dependent GABAergic plasticity modulating slow feed-forward inhibition triggered by top-down, contextual signals in V1. This mechanism can play a significant role in visual perception.
FINANCIAL SUPPORT: Sorbonne Université École doctorale 158 (ED3C) doctoral contract (A.N.); ICM - Institut du Cerveau; Agence Nationale de la Recherche (ANR) ANR-20-CE16-0011-01; ANR-22-CE37-0008-01; ANR-DecoSensoMol1; Equipes FRM – EQU201903007860 (A.B); Émergence programme l’Alliance Sorbonne Université and ANR-21-CE16-0014-01 (J.L.)