title: AAV-Mediated Anterograde Transsynaptic Tagging: Mapping Corticocollicular Input-Defined Neural Pathways for Defense Behaviors.
abstract: 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.
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Neuroscience Graduate Program, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Zingg
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Neuroscience Graduate Program, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Chou
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Department of Physiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Zheng-Gang
authors.initials: ZG
authors.lastname: Zhang
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Neuroscience Graduate Program, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Lukas
authors.initials: L
authors.lastname: Mesik
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Department of Physiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Feixue
authors.initials: F
authors.lastname: Liang
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: htao@usc.edu.
authors.forename: Huizhong Whit
authors.initials: HW
authors.lastname: Tao
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: liizhang@usc.edu.
authors.forename: Li I
authors.initials: LI
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001303:Auditory Cortex / Q000166:cytology / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology; D004254:DNA Nucleotidyltransferases; D000229:Dependovirus; D004924:Escape Reaction / Q000502:physiology*; D046352:Freezing Reaction, Cataleptic / Q000502:physiology*; D019426:Integrases; D051379:Mice; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D013477:Superior Colliculi / Q000166:cytology / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D014793:Visual Cortex / Q000166:cytology / Q000502:physiology*
chemical_list: C045073:Cre recombinase; D004254:DNA Nucleotidyltransferases; C045119:FLP recombinase; D019426:Integrases
keywords: AAV serotypes; Cre and Flp system; corticofugal projection; defensive behavior; flight and freezing; intersectional strategy; mapping neural circuits; superior colliculus; transsynaptic/transneuronal tracer