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      A cross-modality enhancement of defensive flight via parvalbumin neurons in zonal incerta

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          Abstract

          The ability to adjust defensive behavior is critical for animal survival in dynamic environments. However, neural circuits underlying the modulation of innate defensive behavior remain not well-understood. In particular, environmental threats are commonly associated with cues of multiple sensory modalities. It remains to be investigated how these modalities interact to shape defensive behavior. In this study, we report that auditory-induced defensive flight behavior can be facilitated by somatosensory input in mice. This cross-modality modulation of defensive behavior is mediated by the projection from the primary somatosensory cortex (SSp) to the ventral sector of zona incerta (ZIv). Parvalbumin (PV)-positive neurons in ZIv, receiving direct input from SSp, mediate the enhancement of the flight behavior via their projections to the medial posterior complex of thalamus (POm). Thus, defensive flight can be enhanced in a somatosensory context-dependent manner via recruiting PV neurons in ZIv, which may be important for increasing survival of prey animals.

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          Most cited references46

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          High-Performance Genetically Targetable Optical Neural Silencing via Light-Driven Proton Pumps

          The ability to silence the activity of genetically specified neurons in a temporally precise fashion would open up the ability to investigate the causal role of specific cell classes in neural computations, behaviors, and pathologies. Here we show that members of the class of light-driven outward proton pumps can mediate very powerful, safe, multiple-color silencing of neural activity. The gene archaerhodopsin-31 (Arch) from Halorubrum sodomense enables near-100% silencing of neurons in the awake brain when virally expressed in mouse cortex and illuminated with yellow light. Arch mediates currents of several hundred picoamps at low light powers, and supports neural silencing currents approaching 900 pA at light powers easily achievable in vivo. In addition, Arch spontaneously recovers from light-dependent inactivation, unlike light-driven chloride pumps that enter long-lasting inactive states in response to light. These properties of Arch are appropriate to mediate the optical silencing of significant brain volumes over behaviourally-relevant timescales. Arch function in neurons is well tolerated because pH excursions created by Arch illumination are minimized by self-limiting mechanisms to levels comparable to those mediated by channelrhodopsins2,3 or natural spike firing. To highlight how proton pump ecological and genomic diversity may support new innovation, we show that the blue-green light-drivable proton pump from the fungus Leptosphaeria maculans 4 (Mac) can, when expressed in neurons, enable neural silencing by blue light, thus enabling alongside other developed reagents the potential for independent silencing of two neural populations by blue vs. red light. Light-driven proton pumps thus represent a high-performance and extremely versatile class of “optogenetic” voltage and ion modulator, which will broadly empower new neuroscientific, biological, neurological, and psychiatric investigations.
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            AAV-Mediated Anterograde Transsynaptic Tagging: Mapping Corticocollicular Input-Defined Neural Pathways for Defense Behaviors.

            To decipher neural circuits underlying brain functions, viral tracers are widely applied to map input and output connectivity of neuronal populations. Despite the successful application of retrograde transsynaptic viruses for identifying presynaptic neurons of transduced neurons, analogous anterograde transsynaptic tools for tagging postsynaptically targeted neurons remain under development. Here, we discovered that adeno-associated viruses (AAV1 and AAV9) exhibit anterograde transsynaptic spread properties. AAV1-Cre from transduced presynaptic neurons effectively and specifically drives Cre-dependent transgene expression in selected postsynaptic neuronal targets, thus allowing axonal tracing and functional manipulations of the latter input-defined neuronal population. Its application in superior colliculus (SC) reveals that SC neuron subpopulations receiving corticocollicular projections from auditory and visual cortex specifically drive flight and freezing, two different types of defense behavior, respectively. Together with an intersectional approach, AAV-mediated anterograde transsynaptic tagging can categorize neurons by their inputs and molecular identity, and allow forward screening of distinct functional neural pathways embedded in complex brain circuits.
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              Midbrain circuits for defensive behaviour.

              Survival in threatening situations depends on the selection and rapid execution of an appropriate active or passive defensive response, yet the underlying brain circuitry is not understood. Here we use circuit-based optogenetic, in vivo and in vitro electrophysiological, and neuroanatomical tracing methods to define midbrain periaqueductal grey circuits for specific defensive behaviours. We identify an inhibitory pathway from the central nucleus of the amygdala to the ventrolateral periaqueductal grey that produces freezing by disinhibition of ventrolateral periaqueductal grey excitatory outputs to pre-motor targets in the magnocellular nucleus of the medulla. In addition, we provide evidence for anatomical and functional interaction of this freezing pathway with long-range and local circuits mediating flight. Our data define the neuronal circuitry underlying the execution of freezing, an evolutionarily conserved defensive behaviour, which is expressed by many species including fish, rodents and primates. In humans, dysregulation of this 'survival circuit' has been implicated in anxiety-related disorders.
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                Author and article information

                Contributors
                Role: Reviewing Editor
                Role: Senior Editor
                Journal
                eLife
                Elife
                eLife
                eLife
                eLife Sciences Publications, Ltd
                2050-084X
                15 April 2019
                2019
                : 8
                : e42728
                Affiliations
                [1 ]deptZilkha Neurogenetic Institute, Keck School of Medicine University of Southern California Los AngelesUnited States
                [2 ]deptGraduate Program in Neuroscience University of Southern California Los AngelesUnited States
                [3 ]deptGraduate Program in Biomedical and Biological Sciences University of Southern California Los AngelesUnited States
                [4 ]deptDepartment of Physiology and Neuroscience, Keck School of Medicine University of Southern California Los AngelesUnited States
                University of Oxford United Kingdom
                University of Oxford United Kingdom
                University of Oxford United Kingdom
                Vanderbilt United States
                Author notes
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-5805-0778
                https://orcid.org/0000-0002-3660-0513
                Article
                42728
                10.7554/eLife.42728
                6486150
                30985276
                6981e8f3-690e-4781-978a-ebd547880492
                © 2019, Wang et al

                This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 09 October 2018
                : 14 April 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: DC008983
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: EY019049
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100001717, Karl Kirchgessner Foundation;
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: EY022478
                Award Recipient :
                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Research Article
                Neuroscience
                Custom metadata
                Parvalbumin positive GABAergic neurons in the ventral zona incerta receive input from somatosensory cortex and enhance sound-induced flight behavior, which underlies a cross-modality facilitation of defensive behavior by somatosensory input.

                Life sciences
                zona incerta,defensive behavior,parvalbumin,escape,somatosensory,auditory,mouse
                Life sciences
                zona incerta, defensive behavior, parvalbumin, escape, somatosensory, auditory, mouse

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