BDNF controls bidirectional endocannabinoid-plasticity at corticostriatal synapses

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 affect basal ganglia. BDNF/TrkB signaling controls NMDAR-plasticity in various brain structures including striatum. However, despite cross-talks between BDNF and eCBs, the role of BDNF in eCB-plasticity remains unknown. Here, we show that BDNF/TrkB signaling promotes eCB-plasticity (LTD and LTP) induced by rate-based (low-frequency stimulation) or spike-timing-based (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 the dendritic spines combined with patch-clamp recordings, we show that TrkB activation induces an intracellular calcium boost, 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 allows an enlargement of 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.