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.

Community integration after spinal cord injury rehabilitation: Predictors and causal mediators.

CONTEXT/OBJECTIVE: Community integration (CI) is a crucial rehabilitation goal after spinal cord injury (SCI). There is a pressing need to enhance our understanding of the factors associated with CI for individuals with traumatic or non-traumatic etiologies, with the latter being notably understudied. Accordingly, our research explores the associations and potential mediators influencing CI across these populations. SETTING: Specialized neurological rehabilitation center. PARTICIPANTS: Community-dwelling individuals who were admitted as inpatients within 3 months post-injury (n = 431, 51.9% traumatic, 48.1% non-traumatic), assessed in relation to community integration within 1-3 years after discharge. OUTCOME MEASURE: Community Integration Questionnaire (CIQ). Covariates: American Spinal Injury Association Impairment Scale (AIS), Functional Independence Measure (FIM) and Hospital Anxiety and Depression Scale (HADS). RESULTS: Multiple linear regression yielded age, B AIS grade, educational level (< 6 years and <12 years), time since injury to admission, length of stay, HADS-depression at discharge, total FIM at discharge and three social work interventions (support in financial, legal and transportation services) as significant predictors of total CIQ score (Adjusted R2 = 41.4). Multiple logistic regression identified age, traumatic etiology, educational level (< 6 years and <12 years), length of stay, HADS depression at discharge, total FIM at discharge and one social work intervention (transportation support) as significant predictors of good community integration, AUC (95% CI): 0.82 (0.75-0.89), Sensitivity:0.76, Specificity:0.73. We identified motor FIM at discharge and motor FIM efficiency as causal mediators of total CIQ. CONCLUSIONS: We identified modifiable factors during rehabilitation-functional independence, depression, and social work interventions-that are associated with CI.

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.