TY - JOUR
T1 - The 5-HT5A receptor regulates excitability in the auditory startle circuit
T2 - Functional implications for sensorimotor gating
AU - Curtin, Paul C.P.
AU - Medan, Violeta
AU - Neumeister, Heike
AU - Bronson, Daniel R.
AU - Preuss, Thomas
PY - 2013
Y1 - 2013
N2 - Here we applied behavioral testing, pharmacology, and in vivo electrophysiology to determine the function of the serotonin 5-HT5A receptor in goldfish startle plasticity and sensorimotor gating. In an initial series of behavioral experiments, we characterized the effects of a selective 5-HT5A antagonist, SB-699551 (3-cyclopentyl-N-[2-(dimethylamino)ethyl]-N-[(4-{[(2-phenylethyl)amino]methyl}-4- biphenylyl)methyl]propanamide dihydrochloride), on prepulse inhibition of the acoustic startle response. Those experiments showed a dose-dependent decline in startle rates in prepulse conditions. Subsequent behavioral experiments showed that SB-699551 also reduced baseline startle rates (i.e., without prepulse). To determine the cellular mechanisms underlying these behaviors, we tested the effects of two distinct selective 5-HT5A antagonists, SB-699551 and A-843277 (N-(2,6-dimethoxybenzyl)-N'[4-(4-fluorophenyl)thiazol- 2-yl]guanidine), on the intrinsic membrane properties and synaptic sound response of the Mauthner cell (M-cell), the decision-making neuron of the startle circuit. Auditory-evoked postsynaptic potentials recorded in the M-cell were similarly attenuated after treatment with either 5-HT5A antagonist (SB-699551, 26.41±3.98% reduction; A-843277, 17.52±6.24% reduction). This attenuation was produced by a tonic (intrinsic) reduction in M-cell input resistance, likely mediated by a Cl- conductance, that added to the extrinsic inhibition produced by an auditory prepulse. Interestingly, the effector mechanisms underlying neural prepulse inhibition itself were unaffected by antagonist treatment. In summary, these results provide an in vivo electrophysiological characterization of the 5-HT5A receptor and its behavioral relevance and provide a new perspective on the interaction of intrinsic and extrinsic modulatory mechanisms in startle plasticity and sensorimotor gating.
AB - Here we applied behavioral testing, pharmacology, and in vivo electrophysiology to determine the function of the serotonin 5-HT5A receptor in goldfish startle plasticity and sensorimotor gating. In an initial series of behavioral experiments, we characterized the effects of a selective 5-HT5A antagonist, SB-699551 (3-cyclopentyl-N-[2-(dimethylamino)ethyl]-N-[(4-{[(2-phenylethyl)amino]methyl}-4- biphenylyl)methyl]propanamide dihydrochloride), on prepulse inhibition of the acoustic startle response. Those experiments showed a dose-dependent decline in startle rates in prepulse conditions. Subsequent behavioral experiments showed that SB-699551 also reduced baseline startle rates (i.e., without prepulse). To determine the cellular mechanisms underlying these behaviors, we tested the effects of two distinct selective 5-HT5A antagonists, SB-699551 and A-843277 (N-(2,6-dimethoxybenzyl)-N'[4-(4-fluorophenyl)thiazol- 2-yl]guanidine), on the intrinsic membrane properties and synaptic sound response of the Mauthner cell (M-cell), the decision-making neuron of the startle circuit. Auditory-evoked postsynaptic potentials recorded in the M-cell were similarly attenuated after treatment with either 5-HT5A antagonist (SB-699551, 26.41±3.98% reduction; A-843277, 17.52±6.24% reduction). This attenuation was produced by a tonic (intrinsic) reduction in M-cell input resistance, likely mediated by a Cl- conductance, that added to the extrinsic inhibition produced by an auditory prepulse. Interestingly, the effector mechanisms underlying neural prepulse inhibition itself were unaffected by antagonist treatment. In summary, these results provide an in vivo electrophysiological characterization of the 5-HT5A receptor and its behavioral relevance and provide a new perspective on the interaction of intrinsic and extrinsic modulatory mechanisms in startle plasticity and sensorimotor gating.
UR - http://www.scopus.com/inward/record.url?scp=84878858697&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.4733-12.2013
DO - 10.1523/JNEUROSCI.4733-12.2013
M3 - Article
C2 - 23761896
AN - SCOPUS:84878858697
SN - 0270-6474
VL - 33
SP - 10011
EP - 10020
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 24
ER -