Putting forward a model for the role of the cerebellum in cocaine-induced pavlovian memory

Abstract

Substance Use Disorder (SUD) involves emotional, cognitive, and motivational dysfunction. Long-lasting molecular and structural changes in brain regions functionally and anatomically linked to the cerebellum, such as the prefrontal cortex, amygdala, hippocampus, basal ganglia, and ventral tegmental area, are characteristic of SUD. Direct and indirect reciprocal connectivity between the cerebellum and these brain regions can explain cerebellar roles in Pavlovian and reinforcement learning, fear memory, and executive functions. It is increasingly clear that the cerebellum modulates brain functions altered in SUD and other neuropsychiatric disorders that exhibit comorbidity with SUD. In the present manuscript, we review and discuss this evidence and present new research exploring the role of the cerebellum in cocaine-induced conditioned memory using chemogenetic tools (designer receptor exclusively activated by designer drug, DREADDs). Our preliminary data showed that inactivation of a region that includes the interposed and lateral deep cerebellar nuclei reduces the facilitating effect of a posterior vermis lesion on cocaine-induced preference conditioning. These findings support our previous research and suggest that posterior vermis damage may increase drug impact on the addiction circuitry by regulating activity in the DCN. However, they raise further questions that will also be discussed.

Perineuronal Nets in the CNS: Architects of Memory and Potential Therapeutic Target in Neuropsychiatric Disorders

“…These regions notably overlap with brain regions essential for fear-conditioned memory [ 134 ]. Golgi neurons are vital for the modulation of activity and plasticity in the cerebellum, and PNNs surrounding Golgi interneurons play a role in consolidating drug-related memories [ 135 ]. Fully condensed PNNs around Golgi interneurons can label synaptic alignments that represent drug-cue associations [ 135 ].…”

“…Golgi neurons are vital for the modulation of activity and plasticity in the cerebellum, and PNNs surrounding Golgi interneurons play a role in consolidating drug-related memories [ 135 ]. Fully condensed PNNs around Golgi interneurons can label synaptic alignments that represent drug-cue associations [ 135 ]. A recent study showed that cocaine-induced conditioned preference increased neural activity and upregulated PNNs around Golgi interneurons in the posterior cerebellar cortex.…”