A circuit breaking screen identifies gsx1 expressing neurons as required for prepulse inhibition in larval zebrafish

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NICHD	NEURO/BEHAV/SENSYS-2

* FARE Award Winner

Authors

• S.A. Bergeron
• K. Fero
• T. Yokogawa
• M. Hannan
• H. Codore
• H.A. Burgess

Abstract

Prepulse inhibition (PPI) suppresses the startle reflex across vertebrates and occurs when a non-startling stimulus precedes a startling one by a 30-500 ms period, the interstimulus interval (ISI). We used a novel circuit breaking approach to find neuronal mechanisms for PPI. Using a subset of our 240 transgenic enhancer trap lines with Gal4 expression in the CNS, we conditionally ablated defined brain regions with UAS:nitroreductase before testing larvae for PPI. Line xa213 has reduced PPI at long ISI and increased PPI at shorter ISI suggesting the presence of two PPI mechanisms. UAS:Kaede expression in xa213 reveals a column of neurons in the hindbrain reminiscent of known excitatory and inhibitory neurotransmitter stripes. UAS:synaptophysin-RFP expression shows presynaptic punta near the eighth nerve and the Mauthner neuron, two known components of the startle circuit. We mapped the transgene integration site to 21kb upstream of gsx1, and we found that gal4 is co-expressed with gsx1 in xa213. Intriguingly, gsx1 expression is highly conserved between zebrafish and mouse suggesting that this population of neurons plays a similar role in mammals. Our circuit breaking approach is the first to reveal the identity of specific neurons in larval zebrafish that regulate PPI, a clinically relevant behavioral paradigm.

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