Selective effects of Δ9-tetrahydrocannabinol on medium spiny neurons in the striatum.

Derivatives from the Cannabis plant are the most commonly abused illegal substances in the world. The main psychoactive component found in the plant, Δ-9-tetrahydrocannabinol (THC), exerts its effects through the endocannabinoid system. Manipulations of this system affect some types of learning that seem to be dependent on dorsal striatum synaptic plasticity. Dendritic spines exhibit important synaptic functional attributes and a potential for plasticity, which is thought to mediate long-lasting changes in behaviour. To study the possible structural plasticity changes that prolonged THC administration might exert in the dorsal striatum, adult, male C57BL6/J mice were intraperitoneally injected with THC (10mg/kg) or vehicle for 15 days followed by a 7-day drug-free period. Using single cell intracellular injections of Lucifer Yellow, confocal microscopy, and 3D reconstruction of labelled neurons, we studied dendritic spine density and spine size in medium spiny neurons (MSNs) of the anterior dorsolateral striatum (aDLS) and posterior dorsomedial striatum (pDMS). We found that the THC treatment increased dendritic spine density in the distal part of the dendrites of MSNs in the pDMS, but no changes were found in the rest of the parameters analysed in either region studied. We also observed that dendritic spines of MSNs of pDMS presented lower volume and surface area values than MSNs of the aDLS. These results seem to indicate that THC could induce structural plasticity alterations in the circuits involving pDMS MSNs.

Parafascicular thalamic nucleus deep brain stimulation decreases NMDA receptor GluN1 subunit gene expression in the prefrontal cortex.

The rodent parafascicular nucleus (PFn) or the centromedian-parafascicular complex of primates is a posterior intralaminar nucleus of the thalamus related to cortical activation and maintenance of states of consciousness underlying attention, learning and memory. Deep brain stimulation (DBS) of the PFn has been proved to restore arousal and consciousness in humans and to enhance performance in learning and memory tasks in rats. The primary expected effect of PFn DBS is to induce plastic changes in target neurons of brain areas associated with cognitive function. In this study, Wistar rats were stimulated for 20mins in the PFn following a DBS protocol that had previously facilitated memory in rats. NMDA and GABAB receptor binding, and gene expression of the GluN1subunit of the NMDA receptor (NMDAR) were assessed in regions related to cognitive functions, such as the prefrontal cortex and hippocampus. The results showed that PFn DBS induced a decrease in NMDAR GluN1 subunit gene expression in the cingulate and prelimbic cortices, but no significant statistical differences were found in the density of NMDA or GABAB receptors in any of the analyzed regions. Taken together, our findings suggest a possible role for the NMDAR GluN1 subunit in the prefrontal cortex in the procognitive actions of the PFn DBS.