Abstract
The deep and intermediate layers of the superior colliculus (DLSC) respond to visual, auditory, and tactile inputs and act as a multimodal sensory association area. In turn, activity in the DLSC can drive orienting and avoidance responses—such as saccades and head and body movements—across species, including in rats, cats, and non-human primates. As shown in rodents, DLSC also plays a role in regulating pre-pulse inhibition (PPI) of the acoustic startle response (ASR), a form of sensorimotor gating. DLSC lesions attenuate PPI and electrical stimulation of DLSC inhibits the startle response. While the circuitry mediating PPI is well-characterized in rodents, less is known about PPI regulation in primates. Two recent studies from our labs reported a species difference in the effects of pharmacological inhibition of the basolateral amygdala and substantia nigra pars reticulata (SNpr) on PPI between rats and macaques: in rats, inhibition of these structures decreased PPI, while in macaques, it increased PPI. Given that the SNpr sends direct inhibitory projections to DLSC, we next sought to determine if this species difference was similarly evident at the level of DLSC. Here, we transiently inactivated DLSC in four rhesus macaques by focal microinfusion of the GABAA receptor agonist muscimol. Similar to findings reported in rodents, we observed that bilateral inhibition of the DLSC in macaques significantly disrupted PPI. The impairment was specific to the PPI as the ASR itself was not affected. These results indicate that our previously reported species divergence at the level of the SNpr is not due to downstream differences at the level of the DLSC. Species differences at the level of the SNpr and basolateral amygdala emphasize the importance of studying the underlying circuitry in non-human primates, as impairment in PPI has been reported in several disorders in humans, including schizophrenia, autism, and PTSD.
Highlights
Sensorimotor gating—the ability to shift attentional resources to salient stimuli—is often operationalized and studied by assessing pre-pulse inhibition (PPI) of the acoustic startle response (ASR)
In a parallel study employing transient pharmacological inhibition of the substantia nigra pars reticulata (SNpr) in both rodents and non-human primates (Aguilar et al, 2018), we recently reported a surprising divergence of effect—while infusion of the GABAA receptor agonist muscimol into the SNpr disrupts PPI in rodents, we found that the same manipulation potentiates PPI in rhesus macaques, suggesting that the contribution of basal ganglia circuits to PPI may differ between the rodent and primate brain
Given (1) the recent reports of midbrain involvement in post-traumatic stress disorder (PTSD) in clinical populations, and (2) that the DLSC are a primary efferent target of the SNpr, which we have found to differ in function with respect to PPI in rodents and primates, we sought to determine if the previously described species difference in the effect of SNpr inhibition on PPI was present at the level of the DLSC
Summary
Sensorimotor gating—the ability to shift attentional resources to salient stimuli—is often operationalized and studied by assessing pre-pulse inhibition (PPI) of the acoustic startle response (ASR). PPI has been reported to be disrupted in several neuropsychiatric disorders, including schizophrenia, obsessive compulsive disorder, and post-traumatic stress disorder (PTSD) (Grillon et al, 1996; Kohl et al, 2013). In rodents, both permanent lesions and transient pharmacological manipulation of basal ganglia input nuclei (e.g., nucleus accumbens), relay nuclei (e.g., ventral pallidum), and output nuclei (e.g., the substantia nigra pars reticulata; SNpr) disrupt PPI (Wan and Swerdlow, 1993; Kodsi and Swerdlow, 1997; Kretschmer and Koch, 1998; Forcelli et al, 2012; Aguilar et al, 2018). In a parallel study employing transient pharmacological inhibition of the SNpr in both rodents and non-human primates (Aguilar et al, 2018), we recently reported a surprising divergence of effect—while infusion of the GABAA receptor agonist muscimol into the SNpr disrupts PPI in rodents, we found that the same manipulation potentiates PPI in rhesus macaques, suggesting that the contribution of basal ganglia circuits to PPI may differ between the rodent and primate brain
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