Receptor-specific serotonergic modulation of PPI in the acoustic startle pathway in goldfish.

NEUMEISTER, HEIKE; MEDAN, VIOLETA; FICEK, JOSEPH; JOSEPH, NEHEMI; PREUSS, THOMAS

San Diego, CA

Congreso; 40th Annual Meeting of the Society for Neuroscience; 2010

Society for Neuroscience

Prepulse inhibition (PPI), a well-documented sensorimotor-gatingphenomenon observed in many animals including man, is characterized by adecrease in magnitude of a startle reflex if a weak, non-startling stimulus ispresented 20-500 ms before the startling stimulus. Deficits in sensory gatingare implicated inseveral cognitive and information processing disorders, and PPI serves as amajor diagnostic and research tool for these disorders. Recent researchemphasizes serotonin as an important modulator for PPI. However,information about receptor-specific mechanisms is sparse, especially at thecellular level. Our recent work in goldfish has demonstrated a PPI-typeattenuation of the auditory startle response and a corresponding attenuationof the synaptic response in an identifiable reticulospinal neuron, theMauthner cell (M-cell), which triggers the behavior. Moreover, preliminaryresults reveal the expression of the 5-HT receptor subtype 5A in the M-cellof African cichlid fish and we therefore examined its potential role in PPI.Indeed, 5 HTR5A is widely expressed in the vertebrate CNS, however, itsfunctional role is unknown.Intraperitoneal injection of the partly specific 5-HT agonist 5-CT (0.2 and0.5 mg/kg; N=12) significantly reduced the startle responsiveness in a dosedependent manner, but its effects on PPI were inconclusive.Correspondingly, in vivo intracellular recordings from the M-cell afterperfusion with 5-CT showed a dose-dependent reduction (7% for 60 nM;25.2% for 1 μM, p<0.012) of M-cell EPSPs in response to sound pips, but noeffect on cellular PPI.In contrast, the specific 5-HTR5A antagonists SB 699551 significantly(p<0.007; N=10) increased behavioral PPI for prepulse/pulse intervals of 50ms in a dose-dependent manner with mean PPI effects of 53.5%, 85.1%, and92.8% for drug concentrations of 0.5, 0.75, and 0.9 mg/kg, respectively. Aqualitatively similar result was also observed for prepulse/pulse intervals of500 ms (i.e., 53.1%, 86.5% and 83% for 0.5, 0.75, and 0.9 mg/kg,respectively; p<001; N=10)In conclusion, our results suggest a modulatory role of 5-HTR5 insensorimotor gating and, to our knowledge, demonstrates for the first time afunctional role of this receptor subtype in the vertebrate CNS.