A circuit breaking screen identifies gsx1 expressing neurons as modulators of the startle response

Wednesday, November 06, 2013 — Poster Session I
4:00 p.m. – 6:00 p.m.	FAES Academic Center (Upper-Level Terrace)	NICHD	NEURO-2

Authors

S.A. Bergeron
N. Carrier
G. Li
H.A. Burgess

Abstract

Prepulse inhibition (PPI) of the acoustic startle response is used as a measure of how effectively sensory information is processed by the CNS. To identify the neuronal mechanisms for PPI, we used a circuit breaking approach in larval zebrafish. First, we employed a novel technique to enrich for CNS specific expression of Gal4 in many stable transgenic lines. These lines were used to conditionally express a cytotoxin in neurons before testing larvae for PPI. Line y252 showed disrupted PPI which was recapitulated by direct optogenetic inhibition of y252 neurons with archaerhodopsin. In y252, Gal4 is expressed in a column of glutamatergic neurons in the hindbrain that synapse near the command neuron for startle responses, the Mauthner cell. Consistent with a role for glutamate signaling in PPI, pharmacologically blocking NMDA receptors reproduces the y252 phenotype. Finally, in y252 Gal4 is trapped in an enhancer region for gsx1, a homeobox transcription factor expressed in the developing brain in zebrafish and in mouse. Our tests of Gsx1 KO mouse pups revealed that they have reduced PPI compared to wild type siblings. This data supports a model in which Gsx1 derived neurons form an integral part of the PPI circuit across vertebrates.