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BDNF controls bidirectional endocannabinoid-plasticity at corticostriatal synapses

Giuseppe Gangarossa 1 Sylvie Perez 1 Yulia Dembitskaya 1 Ilya Prokin 2, 3 Hugues Berry 2, 3, 4 Laurent Venance 1
2 BEAGLE - Artificial Evolution and Computational Biology
LIRIS - Laboratoire d'InfoRmatique en Image et Systèmes d'information, Inria Grenoble - Rhône-Alpes, LBBE - Laboratoire de Biométrie et Biologie Evolutive - UMR 5558
Abstract : The dorsal striatum exhibits bidirectional corticostriatal synaptic plasticity, NMDAR- and endocannabinoids-(eCB) mediated, necessary for the encoding of procedural learning. Therefore, characterizing factors controlling corticostriatal plasticity is of crucial importance. Brain-derived neurotrophic factor (BDNF) and its receptor, the tropomyosine receptor kinase- B (TrkB), shape striatal functions and their dysfunction deeply affects basal ganglia. BDNF/TrkB signaling controls NMDAR-plasticity in various brain structures including the striatum. However, despite cross-talk between BDNF and eCBs, the role of BDNF in eCBplasticity remains unknown. Here, we show that BDNF/TrkB signaling promotes eCBplasticity (LTD and LTP) induced by rate-based (low-frequency stimulation) or spike-timingbased (spike-timing-dependent plasticity, STDP) paradigm in striatum. We show that TrkB activation is required for the expression and the scaling of both eCB-LTD and eCB-LTP. Using two-photon imaging of dendritic spines combined with patch-clamp recordings, we show that TrkB activation prolongs intracellular calcium transients, thus increasing eCB synthesis and release. We provide a mathematical model for the dynamics of the signaling pathways involved in corticostriatal plasticity. Finally, we show that TrkB activation enlarges the domain of expression of eCB-STDP. Our results reveal a novel role for BDNF/TrkB signaling in governing eCB-plasticity expression in striatum, and thus the engram of procedural learning.
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Submitted on : Thursday, March 21, 2019 - 9:28:27 PM
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Giuseppe Gangarossa, Sylvie Perez, Yulia Dembitskaya, Ilya Prokin, Hugues Berry, et al.. BDNF controls bidirectional endocannabinoid-plasticity at corticostriatal synapses. Cerebral Cortex, Oxford University Press (OUP), 2019, bhz081, pp.1-18. ⟨10.1093/cercor/bhz081⟩. ⟨hal-02076121⟩



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