DevelopmentaUy Transient CBIRs on Cerebellar Afferents Suppress Afferent Input, Downstream Synaptic Excitation, and Signaling to Migrating Neurons.

The endocannabinoid system plays important roles in brain development, but mechanistic studies have focused on neuronal differentiation, migration, and synaptogenesis, with less attention to transcellular interactions that coordinate neurodevelopmental processes across developing neural networks. We determined that, in the developing rodent cerebellar cortex (of both sexes), there is a transient window when the dominant brain cannabinoid receptor, CB1R, is expressed on afferent terminals instead of output neuron Purkinje cell synapses that dominate the adult cerebellum. Activation of these afferent CBIRs suppresses synaptic transmission onto developing granule cells, and consequently also suppresses excitation of downstream neurons in the developing cortical network, including nonsynaptic, migrating neurons. Application of a CB1R antagonist during afferent stimulation trains and depolarizing voltage steps caused a significant, sustained potentiation of synaptic amplitude. Our data demonstrate that transiently expressed afferent CBIRs regulate afferent synaptic strength during synaptogenesis, which enables coordinated dampening of transcortical developmental signals. [ABSTRACT FROM AUTHOR]