Neural Circuits of Sensorimotor Gating and Social Behavior in Nonhuman Primates
Waguespack, Hannah Fay
Forcelli, Patrick A
The nucleus accumbens (NAc) is a critical limbic-motor interface that is important for both processing reward and generating voluntary and reflexive motor outcomes. The NAc receives dense dopaminergic input from the ventral tegmental area and glutamatergic inputs from the amygdala, prefrontal cortex, and hippocampus.In rodents, the NAc is important for processing social reward and is sensitive to both alterations in presynaptic dopamine neurotransmission as well as top-down glutamatergic control from the amygdala. To determine the role of the NAc in processing social reward in primates, the GABAA agonist muscimol and the D2/D3 receptor agonist quinpirole were injected into the NAc of seven macaque animals (eight dyads). Effects of transient inhibition of the NAc with muscimol were dependent on dominance status. Submissive animals displayed an increase in social contact following treatment with muscimol, consistent with reports in rodents. No effect of muscimol on social contact was observed in dominant animals. Interestingly, no effect of dopaminergic manipulation on social contact was detected in either dominant or submissive animals.The NAc is also critical for sensorimotor gating, or the body’s reflexive ability to inhibit a motor response to an external stimulus. Prepulse inhibition (PPI) is a form a sensorimotor gating where a weak prepulse immediately precedes a startling pulse, decreasing the body’s response to the startling stimulus. In rodents, both quinpirole (multiple doses) and muscimol infused into the NAc disrupt PPI. To determine the role of the NAc in PPI in primates, muscimol and three doses of quinpirole were injected bilaterally into the NAc. The highest dose of quinpirole disrupted PPI with a prepulse intensity of 12dB above background. No effect of intra-NAc muscimol infusion on PPI was detected.The deep and intermediate layers of the superior colliculus (DLSC) is a midbrain structure also important for regulating PPI in rodents. Lesions of the superior colliculus disrupt PPI in rodents and capuchin monkeys. To determine the role of the DLSC in regulating PPI in macaques, the structure was transiently inactivated using muscimol. A main effect of muscimol treatment on PPI was detected across prepulse intensities, consistent with prior reports.In this dissertation, I describe a previously unexplored role of the NAc in both sensorimotor and social processing in nonhuman primates. In rodents, there is a vast, complex, and ever-expanding circuit critical for modulating PPI. This circuit incorporates both forebrain and midbrain circuitry. Here, I add to the narrow body of PPI knowledge in nonhuman primates by investigating both the NAc and DLSC, nearly doubling prior reports of targeted manipulation in the context of PPI in primates.
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