A Viral Toolbox of Genetically Encoded Fluorescent Synaptic Tags

Seth Bensussen, Sneha Shankar, Kimberley H. Ching, Dana Zemel, Tina L. Ta, Rebecca A. Mount, Sanaya N. Shroff, Howard J. Gritton, Pierre Fabris, Hannah Vanbenschoten, Connor Beck, Heng Ye Man, Xue Han

Research output: Contribution to journalArticlepeer-review

Abstract

Fibronectin intrabodies generated with mRNA display (FingRs) are a recently developed tool for labeling excitatory or inhibitory synapses, with the benefit of not altering endogenous synaptic protein expression levels or synaptic transmission. Here, we generated a viral vector FingR toolbox that allows for multi-color, neuron-type-specific labeling of excitatory or inhibitory synapses in multiple brain regions. We screened various fluorophores, FingR fusion configurations, and transcriptional control regulations in adeno-associated virus (AAV) and retrovirus vector designs. We report the development of a red FingR variant and demonstrated dual labeling of excitatory and inhibitory synapses in the same cells. Furthermore, we developed cre-inducible FingR AAV variants and demonstrated their utility, finding that the density of inhibitory synapses in aspiny striatal cholinergic interneurons remained unchanged in response to dopamine depletion. Finally, we generated FingR retroviral vectors, which enabled us to track the development of excitatory and inhibitory synapses in hippocampal adult-born granule cells.

Original languageEnglish (US)
Article number101330
JournaliScience
Volume23
Issue number7
DOIs
StatePublished - Jul 24 2020
Externally publishedYes

Keywords

  • Biological Sciences
  • Neuroscience
  • Techniques in Neuroscience

ASJC Scopus subject areas

  • General

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