Cerebellar Activation Bidirectionally Regulates Nucleus Accumbens Medial Shell and Core

Abstract

AbstractTraditionally 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, most studies have focused on cerebellar-cerebral cortical connections, at the expense of subcortical limbic structures. Nothing is known about how the CB connects to the nucleus accumbens (NAc), a subcortical 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 differs in terms of directionality (excitatory vs. inhibitory) and temporal characteristics, in a manner that depends on NAc subregion: in the medial shell of NAc (NAcMed), slow inhibitory responses prevail over excitatory ones, whereas the proportion of fast excitatory responses is greater in the NAc core (NAcCore) compared to NAcMed.Differences also exist in response onset latencies and dependence on CB stimulation intensity, which further 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. We propose that the fast excitatory responses would be well poised to support rapid communication of information critical to the control of motivated behavior, such as prediction or prediction-error signals. The slower, less synchronous and longer-lasting modulation may be suggestive of a regulatory function, such as gain control of the communication between NAc and other brain regions. Finally, 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, which 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.