Waguespack Hannah F, Aguilar Brittany L, Malkova Ludise, Forcelli Patrick A
Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, United States.
Department of Pharmacology & Physiology, Georgetown University, Washington, DC, United States.
Front Behav Neurosci. 2020 Dec 22;14:610702. doi: 10.3389/fnbeh.2020.610702. eCollection 2020.
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 PPI, while in macaques, it 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 GABA 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 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.
上丘深层和中层（DLSC）对视觉、听觉和触觉输入产生反应，并作为一个多模态感觉联合区。相应地，DLSC的活动可以驱动包括大鼠、猫和非人类灵长类动物在内的跨物种的定向和回避反应，如扫视以及头部和身体运动。如在啮齿动物中所示，DLSC在调节听觉惊吓反应（ASR）的前脉冲抑制（PPI）中也起作用，PPI是一种感觉运动门控形式。DLSC损伤会减弱PPI，而对DLSC的电刺激会抑制惊吓反应。虽然在啮齿动物中介导PPI的神经回路已得到充分表征，但在灵长类动物中对PPI调节的了解较少。我们实验室最近的两项研究报告了大鼠和猕猴之间，基底外侧杏仁核和黑质网状部（SNpr）的药理学抑制对PPI影响的物种差异：在大鼠中，抑制这些结构会减弱PPI，而在猕猴中，抑制这些结构会增强PPI。鉴于SNpr向DLSC发送直接的抑制性投射，接下来我们试图确定这种物种差异在DLSC水平上是否同样明显。在这里，我们通过局部微量注射GABA受体激动剂蝇蕈醇，暂时使4只恒河猴的DLSC失活。与在啮齿动物中报道的结果相似，我们观察到猕猴双侧DLSC的抑制显著破坏了PPI。这种损伤是PPI特有的，因为ASR本身不受影响。这些结果表明，我们之前在SNpr水平上报道的物种差异是由于DLSC水平上的下游差异所致。SNpr和基底外侧杏仁核水平上的物种差异强调了研究非人类灵长类动物潜在神经回路的重要性，因为在人类的几种疾病中，包括精神分裂症、自闭症和创伤后应激障碍，都有PPI受损的报道。
