No Discrete Start/Stop Signals in the Dorsal Striatum of Mice Performing a Learned Action.

A popular hypothesis is that the dorsal striatum generates discrete "traffic light" signals that initiate, maintain, and terminate the execution of learned actions. Alternatively, the striatum may continuously monitor the dynamics of movements associated with action execution by processing inputs from somatosensory and motor cortices. Here, we recorded the activity of striatal neurons in mice performing a run-and-stop task and characterized the diversity of firing rate modulations relative to run performance (tuning curves) across neurons. We found that the tuning curves could not be statistically clustered in discrete functional groups (start or stop neurons). Rather, their shape varied continuously according to the movement dynamics of the task. Moreover, striatal spiking activity correlated with running speed on a run-by-run basis and was modulated by task-related non-locomotor movements, such as licking. We hypothesize that such moment-to-moment movement monitoring by the dorsal striatum contributes to the learning of adaptive actions and/or updating their kinematics.

Striatal GABAergic and cortical glutamatergic neurons mediate contrasting effects of cannabinoids on cortical network synchrony.

Activation of type 1 cannabinoid receptors (CB1R) decreases GABA and glutamate release in cortical and subcortical regions, with complex outcomes on cortical network activity. To date there have been few attempts to disentangle the region- and cell-specific mechanisms underlying the effects of cannabinoids on cortical network activity in vivo. Here we addressed this issue by combining in vivo electrophysiological recordings with local and systemic pharmacological manipulations in conditional mutant mice lacking CB1R expression in different neuronal populations. First we report that cannabinoids induce hypersynchronous thalamocortical oscillations while decreasing the amplitude of faster cortical oscillations. Then we demonstrate that CB1R at striatonigral synapses (basal ganglia direct pathway) mediate the thalamocortical hypersynchrony, whereas activation of CB1R expressed in cortical glutamatergic neurons decreases cortical synchrony. Finally we show that activation of CB1 expressed in cortical glutamatergic neurons limits the cannabinoid-induced thalamocortical hypersynchrony. By reporting that CB1R activations in cortical and subcortical regions have contrasting effects on cortical synchrony, our study bridges the gap between cellular and in vivo network effects of cannabinoids. Incidentally, the thalamocortical hypersynchrony we report suggests a potential mechanism to explain the sensory "high" experienced during recreational consumption of marijuana.