A postsynaptic mechanism for dopamine modulation of prepulse inhibition in the goldfish startle circuit.

MEDAN, VIOLETA; PREUSS, THOMAS

Huerta Grande, Córdoba

Congreso; II Reunión Conjunta de Neurociencias Taller-SAN; 2010

Taller de Neurociencias-Sociedad Argentina de Neurociencias

p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0in 0in 0.0001pt; font-size: 12pt; font-family: "Times New Roman"; }div.Section1 { page: Section1; } Startle is a protective behavior against predation, part of the flight/fight response and therefore crucial for survival. Although reflexive, startle is a plastic behavior. One modification of the auditory startle-reflex is prepulse inhibition (PPI), experimentally produced when a startling stimulus (pulse) is preceded within 20-500 ms by a subthreshold stimulus (prepulse) of the same or another modality. Several neurotransmitters modulate PPI in mammals. Notably, dopaminergic (DA) agonists as apomorphine reduce PPI in rats, while antipsychotic drugs as haloperidol reverse this effect. Despite an extensive work on different neurotransmitters effects on behavioral PPI, the neural substrates and cellular mechanisms of its modulation are still unclear. As homologous brainstem circuits mediate mammalian and teleost startles, we decided to investigate the DA influence on PPI in the goldfish primary startle circuit, where an identified pair of reticulospinal neurons (the M-cells) initiates startle. The M-cells decide the likelihood, timing, and direction of escape by integrating inhibitory and excitatory multimodal information. Our work shows that apomorphine decreases M-cell PPI a 25%, while haloperidol restores it to control levels; the PPI reduction is restricted to a time window around 50ms and is mediated by enhancement of an excitatory nonlinear behavior of the M-cell’s membrane. This demonstrates a postsynaptic mechanism for DA modulation of PPI at the primary startle circuit level.