Synthetic cannabinoid-induced changes in thalamo-prefrontal gamma synchrony and thalamic high-voltage spindles

Cannabinoids, including Δ⁹-tetrahydrocannabinol (THC) and potent synthetic analogs, disrupt cognitive and perceptual processes via dysregulated neural oscillations. While these effects within limbic-cortical circuits have been well documented, the contribution of thalamocortical loops, which act as critical hubs for sensory gating and cognitive integration, remains unexplored.

To characterize the effects of acute synthetic cannabinoid exposure on thalamo-prefrontal oscillatory dynamics, specifically focusing on local gamma power, inter-regional synchrony, and cross-frequency coupling relevant.

We performed simultaneous local field potential (LFP) recordings from the mediodorsal thalamus (MD), prelimbic (PrL), and orbitofrontal (OFC) cortices in freely moving rats following acute administration of the potent synthetic cannabinoid 5F-EDMB-PICA (0.3 mg/kg, i.p.).

5F-EDMB-PICA significantly suppressed low- (30-49 Hz) and high-gamma (51-80 Hz) power in PrL and MD, with a transient low-gamma reduction in OFC, while increasing long-range gamma coherence between the MD and prefrontal regions in both sub-bands. Notably, the drug increased the occurrence of high‑voltage spindles (HVS, 6-12 Hz) recorded in the MD, and enhanced phase-amplitude coupling between the phase of both HVS and theta (4-8 Hz) and the amplitude of prefrontal gamma.

These results reveal that acute synthetic cannabinoid exposure produces a dissociation between local and long-range oscillatory dynamics in the thalamo-prefrontal circuit, which possibly is driven by increased thalamic rhythmic output. This pattern of network reorganization may underlie cannabinoid-induced deficits in sensorimotor gating and cognitive integration.