| Title: | Neural correlates of state transitions elicited by a chemosensory danger cue |
| Author(s): | Jesuthasan S; Krishnan S; Cheng RK; Mathuru A; |
| Address: | "Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore; Institute of Molecular and Cell Biology, A*STAR, 61 Biopolis Drive, Singapore. Electronic address: sureshj@ntu.edu.sg. NUS Graduate School of Integrative Sciences and Engineering, National University of Singapore, Singapore. Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore. Institute of Molecular and Cell Biology, A*STAR, 61 Biopolis Drive, Singapore; Yale-NUS College, 12 College Avenue West, Singapore; Dept. of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: ajay.mathuru@yale-nus.edu.sg" |
| Journal Title: | Prog Neuropsychopharmacol Biol Psychiatry |
| DOI: | 10.1016/j.pnpbp.2020.110110 |
| ISSN/ISBN: | 1878-4216 (Electronic) 0278-5846 (Linking) |
| Abstract: | "BACKGROUND: Detection of predator cues changes the brain state in prey species and helps them avoid danger. Dysfunctionality in changing the central state appropriately in stressful situations is proposed to be an underlying cause of multiple psychiatric disorders in humans. METHODS: Here, we investigate the dynamics of neural circuits mediating response to a threat, to characterize these states and to identify potential control networks. We use resonant scanning 2-photon microscopy for in vivo brain-wide imaging and custom designed behavioral assays for the study. RESULTS: We first show that 5-7 day old zebrafish larvae react to an alarm pheromone (Schreckstoff) with reduced mobility. They subsequently display heightened vigilance, as evidenced by increased dark avoidance. Calcium imaging indicates that exposure to Schreckstoff elicits stimulus-locked activity in olfactory sensory neurons innervating a lateral glomerulus and in telencephalic regions including the putative medial amygdala and entopeduncular nucleus. Sustained activity outlasting the stimulus delivery was detected in regions regulating neuromodulator release, including the lateral habenula, posterior tuberculum, superior raphe, and locus coeruleus. CONCLUSION: We propose that these latter regions contribute to the network that defines the 'threatened' state, while neurons with transient activity serve as the trigger. Our study highlights the utility of the zebrafish larval alarm response system to examine neural circuits during stress dependent brain state transitions and to discover potential therapeutic agents when such transitions are disrupted" |
| Keywords: | "Animals *Avoidance Learning Chemoreceptor Cells *Cues Habenula/metabolism Larva/*metabolism Microscopy, Electron Olfactory Receptor Neurons/*metabolism *Pheromones Raphe Nuclei/metabolism Telencephalon/metabolism Zebrafish/*metabolism Behavior change Larv;" |
| Notes: | "MedlineJesuthasan, Suresh Krishnan, Seetha Cheng, Ruey-Kuang Mathuru, Ajay eng Research Support, Non-U.S. Gov't England 2020/09/21 Prog Neuropsychopharmacol Biol Psychiatry. 2021 Dec 20; 111:110110. doi: 10.1016/j.pnpbp.2020.110110. Epub 2020 Sep 18" |
