The ability of animals to detect and generate emotional responses to natural threats is highly innate and conserved cross-species. Appreciated adaptive behavioral responses to different environmental cues are crucial for animal survive. Recent studies have shown that an overhead looming stimulation to mimic an approaching danger can trigger mouse flight behavior and escape to their nest (Yilmaz et al., 2013) or unlearned freezing in the open-field where is “no place to hide” (Wei al., 2015). Our previous work proved the superior colliculus (SC) is the crucial brain structure for rapid responding to this looming threat signal and initialing the visually guided innate defensive responses. By using optogenetic, electrophysiology recording in freeing moving animal, we also identified a subcortical pathway from the glutamatergic projecting neurons in the medial region of the intermediate layers of the SC (ILSCm) to the lateral posterior nucleus of the thalamus (LP) mediating the innate freezing behavior. We further identified a cell specific pathway triggered by visual inputs, promoting appropriate defensive response to overhead visual threats.
While expression of these responses is considered to be instinctive and unconditional, their magnitude may be affected by environmental and internal factors. However, the neural circuits underlying this modulation are still largely unknown. We found that repeated stress caused an anxiety-like state in mice and accelerated defensive responses to looming. Stress also induced c-fos activation in locus coeruleus (LC) TH+ neurons and modified adrenergic receptor expression in SC, suggesting a possible Th::LC-SC projection that may be involved in the accelerated defensive responses. Indeed, both anterograde and retrograde neural tracing confirmed the anatomical Th::LC-SC projection and that the SC-projecting TH+ neurons in LC were activated by repeated stress. Optogenetic stimulation of either LC TH+ neurons or the Th::LC-SC fibers also caused anxiety-like behaviors and accelerated defensive responses to looming. Meanwhile, chemogenetic inhibition of LC TH+ neurons and the infusion of an adrenergic receptor antagonist in SC abolished the enhanced looming defensive responses after repeated stress, confirming the necessity of this pathway. These findings suggest that the Th::LC-SC pathway plays a key role in the sophisticated adjustments of defensive behaviors induced by changes in physiological states.
Liping Wang obtained his PhD degree in medical neuroscience from Max-Delbruck-Center for Molecular Medicine (MDC), Charite-University Medicine, Berlin, Germany, under Prof. Dr. Helmut Kettenmann. Then, he worked as a postdoctoral research fellow at the Department of Bioengineering at Stanford University under Prof. Dr. Karl Deisseroth. He is the director of the Brain Cognition and Brain Disease Institute (BCBDI) for Collaboration Research of SIAT at CAS and the McGovern Institute at MIT, China. His present research is focused on studying the neural circuitry basis of emotion and mental disorders by using the combination of optogenetic probes, in vivo multi-sites electrophysiological recordings, pharmacogenetic manipulations of neuronal activity and virally based trans-synaptic tracing techniques.
Neuroscience Seminar Series by the NYU-ECNU Institute of Brain and Cognitive Science at NYU Shanghai