Investigating a mammalian inhibitory circuit for distractor suppression

项目总结

Project Summary Operating in complex environments, animals selectively process the most important (highest ‘priority’) stimulus to guide behavior, while ignoring distracting stimuli at all other spatial locations. This ability, called spatial selective attention, is critical for behavior and even survival. Converging evidence from primates and birds has implicated the midbrain superior colliculus (SC in mammals; optic tectum – OT in birds)2,3 as a critical node for the control of spatial attention when multiple competing targets are present. Studies also show that competitive interactions among stimuli are encoded in the intermediate and deep layers of the SC (SCid; OTid in birds), with stimulus competition manifesting as the suppression of the responses of each stimulus by competing stimuli. Additionally, recent work in birds (by the Mysore Lab and others) has revealed that such competitive interactions within the OTid are controlled by a group of parvalbumin positive (PV+) inhibitory neurons in the avian midbrain tegmentum called nucleus isthmi pars magnocellularis (Imc). The Imc connects with the OT in a specialized manner and drives long-range suppression of OTid responses by competing stimuli 4-6, leading to the suggestion that, in birds, the Imc may serve to suppress distracters and facilitate the selection of the target of spatial attention1,5,7. However, not only is the inhibitory source for similar long-range competitive interactions in the mammalian SCid unknown, but also the specific circuit mechanisms underlying distractor suppression and target selection for spatial selective attention in any animal are yet to be discovered11. Here, I will address these questions in mice by investigating the function of the peri-parabigeminal lateral tegmental nucleus (pLTN), which is thought to be mammalian homolog of the Imc1,12,13. Specifically, in Aim 1, I will use focal cell type-specific optogenetic manipulations of the PV+ pLTN, coupled with SCid electrophysiology in head-fixed, passive-viewing mice to test if pLTN neurons are responsible for controlling competitive interactions in the SCid. I predict that silencing pLTN neurons will abolish stimulus competition within SCid. Next, in Aim 2, I will leverage a new behavioral paradigm developed in the lab for the study of primate-like visuospatial selective attention in freely behaving mice14, and using cell-type specific optogenetic manipulation, investigate the causal role of pLTN in distractor suppression and target selection. I predict that optogenetic activation of the portion of pLTN encoding the target will cause hyper-attention (resistance to distractibility), whereas optogenetic inactivation of the portion of the pLTN encoding the target with cause hyper-distractibility. These results will reveal, for the first time, neural circuit mechanisms for the control of distracter suppression for spatial attention, and can shed light on the circuit basis of the debilitating attentional dysfunction found in psychiatric conditions such as ADHD and schizophrenia.