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.

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.annabinoids are a family of compounds that activate cannabinoid receptors, which are well known for their psychotropic effects and therapeutic potentials. The type 1 cannabinoid receptor (CB1R) is massively expressed in the brain at the synaptic terminals of excitatory and inhibitory neurons, and its activation by exogenous or endogenous cannabinoids decreases neurotransmitter release (1-3). One largely unanswered question is how the elementary decreases in excitatory and inhibitory synaptic transmissions induced by systemic intake of cannabinoids interact to produce alterations in neuronal network activity in vivo. A number of recent studies combining systemic injections of CB1R agonists and antagonists with electrophysiological recordings in the hippocampus and neocortex of awake or anesthetized rodents have shown that a hallmark of cannabinoids effects on neuronal network activity is a decrease in synchrony (4-9). Specifically, systemic CB1R activation has been shown to decrease (i) the amplitude of the hippocampal θ rhythm (4, 7, 8), (ii) the amplitude of γ oscillations in the hippocampus (4, 7, 10), enthorinal cortex (8), and prefrontal cortex (7), (iii) the incidence of hippocampal ripples (4, 6, 11), and (iv) spiking correlation in the hippocampus and prefrontal cortex (4,5,7,9).In contrast to the consistent reports that cannabinoids dampen cortical network oscillations, other findings suggest that they could also increase synchrony. First, CB1R are predominantly expressed by GABAergic forebrain neurons (12), and their activation leads to decreased GABA ...