David J Marcus, Anthony E English, Gunn Chun, Emmaline F Seth, Rachel Oommen, Sabrina Hwang, Bailey A Wells, Sean C Piantadosi, Azra Suko, Sayaka J Kenmochi, Anupritaa A Parasnis, Ethan Ancell, Yulong Li, Larry S Zweifel, Benjamin B Land, Nephi Stella, Michael R Bruchas
Neuromodulatory signalling is poised to serve as a neural mechanism for gain control, acting as a crucial tuning factor to influence neuronal activity by dynamically shaping excitatory and inhibitory fast neurotransmission. The endocannabinoid (eCB) signalling system, the most widely expressed neuromodulatory system in the mammalian brain, has been demonstrated to filter excitatory and inhibitory inputs through retrograde, presynaptic action in vitro and ex vivo1-9. However, whether eCBs exert retrograde gain control to ultimately facilitate motivated behaviours in freely moving mammals has not been established. Here, using a suite of in vivo physiological, imaging, genetic and machine learning-based approaches, we uncover a fundamental role for the dynamic release of eCBs in controlling behavioural engagement during reward seeking through a genetically and anatomically defined thalamostriatal circuit.