Cerebellar Activation Bidirectionally Regulates Nucleus Accumbens Shell and Core

Traditionally viewed as a motor control center, the cerebellum (CB) is now recognized as an integral part of a broad, long-range brain network that serves limbic functions and motivates behavior. This diverse CB functionality has been at least partly attributed to the multiplicity of its outputs. However, relatively little attention has been paid to CB connectivity with subcortical limbic structures, and nothing is known about how the CB connects to the nucleus accumbens (NAc), a complex striatal region with which the CB shares functionality in motivated behaviors. Here, we report findings from in vivo electrophysiological experiments that investigated the functional connectivity between CB and NAc. We found that electrical microstimulation of deep cerebellar nuclei (DCN) modulates NAc spiking activity. This modulation differed in terms of directionality (excitatory vs. inhibitory) and temporal characteristics, in a manner that depends on NAc subregions: in the medial shell of NAc (NAcMed), slow inhibitory responses prevailed over excitatory ones, whereas the proportion of fast excitatory responses was greater in the NAc core (NAcCore) compared to NAcMed. Slow inhibitory modulation of NAcCore was also observed but it required stronger CB inputs compared to NAcMed. Finally, we observed shorter onset latencies for excitatory responses in NAcCore than in NAcMed, which argues for differential connectivity. If different pathways provide signal to each subregion, the divergence likely occurs downstream of the CB because we did not find any response-type clustering within DCN. Because there are no direct monosynaptic connections between CB and NAc, we performed viral tracing experiments to chart disynaptic pathways that could potentially mediate the newly discovered CB-NAc communication. We identified two anatomical pathways that recruit the ventral tegmental area and intralaminar thalamus as nodes. These pathways and the functional connectivity they support could underlie the role of the CB in motivated behaviors.