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Tonically active GABAergic neurons in the dorsal periaqueductal gray control instinctive escape in mice

斯科普斯 神经科学 捕食 心理学 生物 生态学 梅德林 生物化学
作者
A. Vanessa Stempel,Dominic A. Evans,Oriol Pavón Arocas,Federico Claudi,Stephen C. Lenzi,Elena Kutsarova,Troy W. Margrie,Tiago Branco
出处
期刊:Current Biology [Elsevier BV]
标识
DOI:10.1016/j.cub.2024.05.068
摘要

Escape behavior is a set of locomotor actions that move an animal away from threat. While these actions can be stereotyped, it is advantageous for survival that they are flexible.1Evans D.A. Stempel A.V. Vale R. Branco T. Cognitive control of escape behaviour.Trends Cogn. Sci. 2019; 23: 334-348Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar,2Edwards D.H. Heitler W.J. Krasne F.B. Fifty years of a command neuron: The neurobiology of escape behavior in the crayfish.Trends Neurosci. 1999; 22: 153-161Abstract Full Text Full Text PDF PubMed Scopus (260) Google Scholar,3Peek M.Y. Card G.M. Comparative approaches to escape.Curr. Opin. Neurobiol. 2016; 41: 167-173Crossref PubMed Scopus (49) Google Scholar For example, escape probability depends on predation risk and competing motivations,4Lima S.L. Dill L.M. Behavioral decisions made under the risk of predation: a review and prospectus.Can. J. Zool. 1990; 68: 619-640Crossref Google Scholar,5Collier A. Hodgson J.Y. A shift in escape strategy by grasshopper prey in response to repeated pursuit.Southeastern Nat. 2017; 16: 503-515Crossref Scopus (3) Google Scholar,6Cooper W.E. Frederick W.G. Optimal flight initiation distance.J. Theor. Biol. 2007; 244: 59-67Crossref PubMed Scopus (318) Google Scholar,7Edut S. Eilam D. Rodents in open space adjust their behavioral response to the different risk levels during barn-owl attack.BMC Ecol. 2003; 3: 10Crossref PubMed Scopus (42) Google Scholar,8Filosa A. Barker A.J. Dal Maschio M. Baier H. Feeding state modulates behavioral choice and processing of prey stimuli in the zebrafish tectum.Neuron. 2016; 90: 596-608Abstract Full Text Full Text PDF PubMed Google Scholar,9Azevedo E.P. Tan B. Pomeranz L.E. Ivan V. Fetcho R. Schneeberger M. Doerig K.R. Liston C. Friedman J.M. Stern S.A. A limbic circuit selectively links active escape to food suppression.eLife. 2020; 9e58894Crossref Google Scholar,10de Araujo Salgado I. Li C. Burnett C.J. Rodriguez Gonzalez S. Becker J.J. Horvath A. Earnest T. Kravitz A.V. Krashes M.J. Toggling between food-seeking and self-preservation behaviors via hypothalamic response networks.Neuron. 2023; 111: 2899-2917.e6Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar,11Cooper W.E.J. Blumstein D.T. Escaping from Predators: An Integrative View of Escape Decisions. Cambridge University Press, 2015Crossref Google Scholar and flight to safety requires continuous adjustments of trajectory and must terminate at the appropriate place and time.12Blank D.A. Escaping behavior in goitered gazelle.Behav. Processes. 2018; 147: 38-47Crossref PubMed Scopus (8) Google Scholar,13Claudi F. Campagner D. Branco T. Innate heuristics and fast learning support escape route selection in mice.Curr. Biol. 2022; 32: 2980--2987.e5Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar,14Domenici P. Blagburn J.M. Bacon J.P. Animal escapology I: theoretical issues and emerging trends in escape trajectories.J. Exp. Biol. 2011; 214: 2463-2473Crossref PubMed Scopus (141) Google Scholar,15Eilam D. Die hard: A blend of freezing and fleeing as a dynamic defense - Implications for the control of defensive behavior.Neurosci. Biobehav. Rev. 2005; 29: 1181-1191Crossref PubMed Scopus (177) Google Scholar,16Shamash P. Olesen S.F. Iordanidou P. Campagner D. Banerjee N. Branco T. Mice learn multi-step routes by memorizing subgoal locations.Nat. Neurosci. 2021; 24: 1270-1279Crossref PubMed Scopus (15) Google Scholar This degree of flexibility suggests that modulatory components, like inhibitory networks, act on the neural circuits controlling instinctive escape.17Lefler Y. Campagner D. Branco T. The role of the periaqueductal gray in escape behavior.Curr. Opin. Neurobiol. 2020; 60: 115-121Crossref PubMed Scopus (44) Google Scholar,18Depaulis A. Bandler R. The Midbrain Periaqueductal Gray Matter: Functional, Anatomical, and Neurochemical Organization. Springer, 1991Crossref Google Scholar,19Shaikh M.B. Siegel A. GABA-mediated regulation of feline aggression elicited from midbrain periaqueductal gray.Brain Res. 1990; 507: 51-56Crossref PubMed Scopus (0) Google Scholar,20Behbehani M.M. Jiang M. Chandler S.D. Ennis M. The effect of GABA and its antagonists on midbrain periaqueductal gray neurons in the rat.Pain. 1990; 40: 195-204Abstract Full Text PDF PubMed Scopus (105) Google Scholar,21Silva B.A. Gross C.T. Gräff J. The neural circuits of innate fear: detection, integration, action, and memorization.Learn. Mem. 2016; 23: 544-555Crossref PubMed Scopus (104) Google Scholar,22Fratzl A. Koltchev A.M. Vissers N. Tan Y.L. Marques-Smith A. Stempel A.V. Branco T. Hofer S.B. Flexible inhibitory control of visually evoked defensive behavior by the ventral lateral geniculate nucleus.Neuron. 2021; 109: 3810-3822.e9Abstract Full Text Full Text PDF PubMed Google Scholar In mice, the decision to escape from imminent threats is implemented by a feedforward circuit in the midbrain, where excitatory vesicular glutamate transporter 2-positive (VGluT2+) neurons in the dorsal periaqueductal gray (dPAG) compute escape initiation and escape vigor.23Tovote P. Esposito M.S. Botta P. Chaudun F. Fadok J.P. Markovic M. Wolff S.B.E. Ramakrishnan C. Fenno L. Deisseroth K. et al.Midbrain circuits for defensive behaviour.Nature. 2016; 534: 206-212Crossref PubMed Scopus (452) Google Scholar,24Evans D.A. Stempel A.V. Vale R. Ruehle S. Lefler Y. Branco T. A synaptic threshold mechanism for computing escape decisions.Nature. 2018; 558: 590-594Crossref PubMed Scopus (256) Google Scholar,25Deng H. Xiao X. Wang Z. Periaqueductal gray neuronal activities underlie different aspects of defensive behaviors.J. Neurosci. 2016; 36: 7580-7588Crossref PubMed Scopus (125) Google Scholar Here we tested the hypothesis that local GABAergic neurons within the dPAG control escape behavior by setting the excitability of the dPAG escape network. Using in vitro patch-clamp and in vivo neural activity recordings, we found that vesicular GABA transporter-positive (VGAT+) dPAG neurons fire action potentials tonically in the absence of synaptic inputs and are a major source of inhibition to VGluT2+ dPAG neurons. Activity in VGAT+ dPAG cells transiently decreases at escape onset and increases during escape, peaking at escape termination. Optogenetically increasing or decreasing VGAT+ dPAG activity changes the probability of escape when the stimulation is delivered at threat onset and the duration of escape when delivered after escape initiation. We conclude that the activity of tonically firing VGAT+ dPAG neurons sets a threshold for escape initiation and controls the execution of the flight action.

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