PMID- 32198185
OWN - NLM
STAT- MEDLINE
DCOM- 20200923
LR  - 20240214
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 40
IP  - 16
DP  - 2020 Apr 15
TI  - Synaptic Specificity and Application of Anterograde Transsynaptic AAV for Probing 
      Neural Circuitry.
PG  - 3250-3267
LID - 10.1523/JNEUROSCI.2158-19.2020 [doi]
AB  - Revealing the organization and function of neural circuits is greatly facilitated 
      by viral tools that spread transsynaptically. Adeno-associated virus (AAV) 
      exhibits anterograde transneuronal transport, however, the synaptic specificity 
      of this spread and its broad application within a diverse set of circuits remains 
      to be explored. Here, using anatomic, functional, and molecular approaches, we 
      provide evidence for the preferential transport of AAV1 to postsynaptically 
      connected neurons and reveal its spread is strongly dependent on synaptic 
      transmitter release. In addition to glutamatergic pathways, AAV1 also spreads 
      through GABAergic synapses to both excitatory and inhibitory cell types. We 
      observed little or no transport, however, through neuromodulatory projections 
      (e.g., serotonergic, cholinergic, and noradrenergic). In addition, we found that 
      AAV1 can be transported through long-distance descending projections from various 
      brain regions to effectively transduce spinal cord neurons. Combined with newly 
      designed intersectional and sparse labeling strategies, AAV1 can be applied 
      within a wide variety of pathways to categorize neurons according to their input 
      sources, morphology, and molecular identities. These properties make AAV1 a 
      promising anterograde transsynaptic tool for establishing a comprehensive 
      cell-atlas of the brain, although its capacity for retrograde transport currently 
      limits its use to unidirectional circuits.SIGNIFICANCE STATEMENT The discovery of 
      anterograde transneuronal spread of AAV1 generates great promise for its 
      application as a unique tool for manipulating input-defined cell populations and 
      mapping their outputs. However, several outstanding questions remain for 
      anterograde transsynaptic approaches in the field: (1) whether AAV1 spreads 
      exclusively or specifically to synaptically connected neurons, and (2) how broad 
      its application could be in various types of neural circuits in the brain. This 
      study provides several lines of evidence in terms of anatomy, functional 
      innervation, and underlying mechanisms, to strongly support that AAV1 anterograde 
      transneuronal spread is highly synapse specific. In addition, several potentially 
      important applications of transsynaptic AAV1 in probing neural circuits are 
      described.
CI  - Copyright (c) 2020 the authors.
FAU - Zingg, Brian
AU  - Zingg B
AD  - Zilkha Neurogenetic Institute.
AD  - Neuroscience Graduate Program, Keck School of Medicine, University of Southern 
      California, Los Angeles, California 90033.
FAU - Peng, Bo
AU  - Peng B
AD  - Zilkha Neurogenetic Institute.
AD  - Neuroscience Graduate Program, Keck School of Medicine, University of Southern 
      California, Los Angeles, California 90033.
FAU - Huang, Junxiang
AU  - Huang J
AD  - Zilkha Neurogenetic Institute.
AD  - Neuroscience Graduate Program, Keck School of Medicine, University of Southern 
      California, Los Angeles, California 90033.
FAU - Tao, Huizhong W
AU  - Tao HW
AD  - Zilkha Neurogenetic Institute liizhang@usc.edu htao@usc.edu.
AD  - Department of Physiology and Neuroscience.
FAU - Zhang, Li I
AU  - Zhang LI
AD  - Zilkha Neurogenetic Institute liizhang@usc.edu htao@usc.edu.
AD  - Department of Physiology and Neuroscience.
LA  - eng
GR  - R21 EY022478/EY/NEI NIH HHS/United States
GR  - R01 DC008983/DC/NIDCD NIH HHS/United States
GR  - R01 EY019049/EY/NEI NIH HHS/United States
GR  - RF1 MH114112/MH/NIMH NIH HHS/United States
GR  - R01 EY025722/EY/NEI NIH HHS/United States
GR  - U01 MH116990/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20200320
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
SB  - IM
MH  - Animals
MH  - Axonal Transport/*physiology
MH  - Dependovirus
MH  - Neural Pathways/physiology
MH  - Neurons/*physiology
MH  - Synapses/*physiology
PMC - PMC7159884
EDAT- 2020/03/22 06:00
MHDA- 2020/09/24 06:00
PMCR- 2020/10/15
CRDT- 2020/03/22 06:00
PHST- 2019/09/06 00:00 [received]
PHST- 2020/03/05 00:00 [revised]
PHST- 2020/03/08 00:00 [accepted]
PHST- 2020/03/22 06:00 [pubmed]
PHST- 2020/09/24 06:00 [medline]
PHST- 2020/03/22 06:00 [entrez]
PHST- 2020/10/15 00:00 [pmc-release]
AID - JNEUROSCI.2158-19.2020 [pii]
AID - JN-RM-2158-19 [pii]
AID - 10.1523/JNEUROSCI.2158-19.2020 [doi]
PST - ppublish
SO  - J Neurosci. 2020 Apr 15;40(16):3250-3267. doi: 10.1523/JNEUROSCI.2158-19.2020. 
      Epub 2020 Mar 20.