A Chemogenetic Tool that Enables Functional Neural Circuit Analysis.

Abstract:

:Chemogenetics enables manipulation of neuronal activity in experimental animals. While providing information about the transduced neuron expressing a ligand-activated molecule, chemogenetics does not provide understanding about the antecedent circuit that drives that neuron's activity. For current approaches, this is not feasible, because the activating molecules are not genetically encoded. The insect allatostatin/allatostatin receptor system, a highly specific, powerful inhibitory chemogenetic approach, has this advantage, because the ligand, being a peptide, is genetically encoded. We developed viral vector-based systems to express biologically active allatostatin in neurons in vivo and allatostatin receptors in subpopulations of postsynaptic neurons. We demonstrate that activity-dependent release of allatostatin induces inhibition of allatostatin receptor-expressing neurons. We validate the approach in the vagal viscerosensory system where inhibitory, rather than the usual excitatory, viscerosensory input leads to sustained decreases in baroreceptor reflex sensitivity and bodyweight.

journal_name

Cell Rep

journal_title

Cell reports

authors

Ngo HB,Melo MR,Layfield S,Connelly AA,Bassi JK,Xie L,Menuet C,McDougall SJ,Bathgate RAD,Allen AM

doi

10.1016/j.celrep.2020.108139

subject

Has Abstract

pub_date

2020-09-15 00:00:00

pages

108139

issue

11

issn

2211-1247

pii

S2211-1247(20)31128-1

journal_volume

32

pub_type

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