Integrating endocannabinoid signaling, CCK interneurons, and hippocampal circuit dynamics in behaving animals

The brain's endocannabinoid signaling system modulates a diverse range of physiological phenomena and is also involved in various psychiatric and neurological disorders. The basic components of the molecular machinery underlying endocannabinoid-mediated synaptic signaling have been known for decades. However, limitations associated with the short-lived nature of endocannabinoid lipid signals had made it challenging to determine the spatiotemporal specificity and dynamics of endocannabinoid signaling in vivo. Here, we discuss how novel technologies have recently enabled unprecedented insights into endocannabinoid signaling taking place at specific synapses in behaving animals. In this review, we primarily focus on cannabinoid-sensitive inhibition in the hippocampus in relation to place cell properties to illustrate the potential of these novel methodologies. In addition, we highlight implications of these approaches and insights for the unraveling of cannabinoid regulation of synapses in vivo in other brain circuits in both health and disease.