Endogenous cannabinoid signaling at inhibitory interneurons

•Endocannabinoids (eCBs) are powerful modulators of inhibitory synaptic transmission.•eCBs control inhibitory synapses in an activity-dependent (i.e. phasic) or tonic manner.•By regulating inhibitory microcircuits, eCB signaling contributes to behavior.•Dysregulated eCB signaling contributes to common neuropsychiatric conditions.

Significant progress has been made in our understanding of how endogenous cannabinoids (eCBs) signal at excitatory and inhibitory synapses in the central nervous system (CNS). This review discusses how eCBs regulate inhibitory interneurons, their synapses, and the networks in which they are embedded. eCB signaling plays a pivotal role in brain physiology by means of their synaptic signal transduction, spatiotemporal signaling profile, routing of information through inhibitory microcircuits, and experience-dependent plasticity. Understanding the normal processes underlying eCB signaling is beginning to shed light on how their dysregulation contributes to disease.