PMID- 38096019 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20231216 IS - 2050-084X (Electronic) IS - 2050-084X (Linking) VI - 12 DP - 2023 Dec 14 TI - Postsynaptic cell type and synaptic distance do not determine efficiency of monosynaptic rabies virus spread measured at synaptic resolution. LID - 10.7554/eLife.89297 [doi] LID - e89297 AB - Retrograde monosynaptic tracing using glycoprotein-deleted rabies virus is an important component of the toolkit for investigation of neural circuit structure and connectivity. It allows for the identification of first-order presynaptic connections to cell populations of interest across both the central and peripheral nervous system, helping to decipher the complex connectivity patterns of neural networks that give rise to brain function. Despite its utility, the factors that influence the probability of transsynaptic rabies spread are not well understood. While it is well established that expression levels of rabies glycoprotein used to trans-complement G-deleted rabies can result in large changes in numbers of inputs labeled per starter cell (convergence index [CI]), it is not known how typical values of CI relate to the proportions of synaptic contacts or input neurons labeled. And it is not known whether inputs to different cell types, or synaptic contacts that are more proximal or distal to the cell body, are labeled with different probabilities. Here, we use a new rabies virus construct that allows for the simultaneous labeling of pre- and postsynaptic specializations to quantify the proportion of synaptic contacts labeled in mouse primary visual cortex. We demonstrate that with typical conditions about 40% of first-order presynaptic excitatory synapses to cortical excitatory and inhibitory neurons are labeled. We show that using matched tracing conditions there are similar proportions of labeled contacts onto L4 excitatory pyramidal, somatostatin (Sst) inhibitory, and vasoactive intestinal peptide (Vip) starter cell types. Furthermore, we find no difference in the proportions of labeled excitatory contacts onto postsynaptic sites at different subcellular locations. CI - (c) 2023, Patino et al. FAU - Patino, Maribel AU - Patino M AUID- ORCID: 0000-0003-0820-3315 AD - Systems Neurobiology Laboratories, The Salk Institute for Biological Studies, La Jolla, United States. AD - Neuroscience Graduate Program, University of California, San Diego, La Jolla, United States. AD - Medical Scientist Training Program, University of California, San Diego, La Jolla, United States. FAU - Lagos, Willian N AU - Lagos WN AD - Systems Neurobiology Laboratories, The Salk Institute for Biological Studies, La Jolla, United States. FAU - Patne, Neelakshi S AU - Patne NS AD - Systems Neurobiology Laboratories, The Salk Institute for Biological Studies, La Jolla, United States. FAU - Miyazaki, Paula A AU - Miyazaki PA AD - Systems Neurobiology Laboratories, The Salk Institute for Biological Studies, La Jolla, United States. FAU - Bhamidipati, Sai Krishna AU - Bhamidipati SK AUID- ORCID: 0000-0003-3498-3730 AD - Systems Neurobiology Laboratories, The Salk Institute for Biological Studies, La Jolla, United States. FAU - Collman, Forrest AU - Collman F AUID- ORCID: 0000-0002-0280-7022 AD - Allen Institute for Brain Science, Seattle, United States. FAU - Callaway, Edward M AU - Callaway EM AUID- ORCID: 0000-0002-6366-5267 AD - Systems Neurobiology Laboratories, The Salk Institute for Biological Studies, La Jolla, United States. LA - eng GR - R01 EY022577/EY/NEI NIH HHS/United States GR - T32 GM007198/GM/NIGMS NIH HHS/United States GR - U24 NS120053/NS/NINDS NIH HHS/United States GR - U24NS120053/NS/NINDS NIH HHS/United States PT - Journal Article DEP - 20231214 PL - England TA - Elife JT - eLife JID - 101579614 RN - 0 (Glycoproteins) SB - IM UOF - doi: 10.1101/2022.08.31.506012 MH - Mice MH - Animals MH - *Rabies virus MH - *Rabies MH - Neurons/physiology MH - Synapses/physiology MH - Glycoproteins/metabolism PMC - PMC10721217 OTO - NOTNLM OT - cerebral cortex OT - interneuron OT - mouse OT - neural circuit OT - neuroscience OT - rabies virus OT - synapse COIS- MP, WL, NP, PM, SB, FC, EC No competing interests declared EDAT- 2023/12/14 12:42 MHDA- 2023/12/17 09:46 PMCR- 2023/12/14 CRDT- 2023/12/14 11:54 PHST- 2023/05/11 00:00 [received] PHST- 2023/11/19 00:00 [accepted] PHST- 2023/12/17 09:46 [medline] PHST- 2023/12/14 12:42 [pubmed] PHST- 2023/12/14 11:54 [entrez] PHST- 2023/12/14 00:00 [pmc-release] AID - 89297 [pii] AID - 10.7554/eLife.89297 [doi] PST - epublish SO - Elife. 2023 Dec 14;12:e89297. doi: 10.7554/eLife.89297.