The 5-HT5A receptor regulates excitability in the auditory startle circuit: Functional implications for sensorimotor gating
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 antago...
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todo:paper_02706474_v33_n24_p10011_Curtin2023-10-03T15:14:44Z The 5-HT5A receptor regulates excitability in the auditory startle circuit: Functional implications for sensorimotor gating Curtin, P.C.P. Medan, V. Neumeister, H. Bronson, D.R. Preuss, T. serotonin 5A receptor serotonin antagonist biphenyl derivative guanidine derivative N (2,6 dimethoxybenzyl) N' (4 (4 fluorophenyl)thiazol 2 yl)guanidine N-(2,6-dimethoxybenzyl)-N'-(4-(4-fluorophenyl)thiazol-2-yl)guanidine potassium chloride SB 699551 A SB-699551-A serotonin 5 receptor serotonin antagonist serotonin receptor thiazole derivative animal experiment article auditory stimulation behavior brain electrophysiology chloride conductance controlled study evoked auditory response excitatory postsynaptic potential goldfish Mauthner cell nerve cell excitability nerve cell membrane steady potential nerve cell plasticity nonhuman prepulse inhibition priority journal sensory gating startle reflex swimming acoustics animal cytology dose response drug effect electrostimulation evoked auditory response female inhibitory postsynaptic potential male metabolism methodology nerve cell nerve cell inhibition nerve cell network nerve tract patch clamp physiology sensory gating spinal cord time Acoustic Stimulation Acoustics Animals Biphenyl Compounds Dose-Response Relationship, Drug Electric Stimulation Evoked Potentials, Auditory Excitatory Postsynaptic Potentials Female Goldfish Guanidines Inhibitory Postsynaptic Potentials Male Nerve Net Neural Inhibition Neural Pathways Neurons Patch-Clamp Techniques Potassium Chloride Receptors, Serotonin Sensory Gating Serotonin Antagonists Spinal Cord Startle Reaction Thiazoles Time Factors 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. © 2013 the authors. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_02706474_v33_n24_p10011_Curtin |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
serotonin 5A receptor serotonin antagonist biphenyl derivative guanidine derivative N (2,6 dimethoxybenzyl) N' (4 (4 fluorophenyl)thiazol 2 yl)guanidine N-(2,6-dimethoxybenzyl)-N'-(4-(4-fluorophenyl)thiazol-2-yl)guanidine potassium chloride SB 699551 A SB-699551-A serotonin 5 receptor serotonin antagonist serotonin receptor thiazole derivative animal experiment article auditory stimulation behavior brain electrophysiology chloride conductance controlled study evoked auditory response excitatory postsynaptic potential goldfish Mauthner cell nerve cell excitability nerve cell membrane steady potential nerve cell plasticity nonhuman prepulse inhibition priority journal sensory gating startle reflex swimming acoustics animal cytology dose response drug effect electrostimulation evoked auditory response female inhibitory postsynaptic potential male metabolism methodology nerve cell nerve cell inhibition nerve cell network nerve tract patch clamp physiology sensory gating spinal cord time Acoustic Stimulation Acoustics Animals Biphenyl Compounds Dose-Response Relationship, Drug Electric Stimulation Evoked Potentials, Auditory Excitatory Postsynaptic Potentials Female Goldfish Guanidines Inhibitory Postsynaptic Potentials Male Nerve Net Neural Inhibition Neural Pathways Neurons Patch-Clamp Techniques Potassium Chloride Receptors, Serotonin Sensory Gating Serotonin Antagonists Spinal Cord Startle Reaction Thiazoles Time Factors |
| spellingShingle |
serotonin 5A receptor serotonin antagonist biphenyl derivative guanidine derivative N (2,6 dimethoxybenzyl) N' (4 (4 fluorophenyl)thiazol 2 yl)guanidine N-(2,6-dimethoxybenzyl)-N'-(4-(4-fluorophenyl)thiazol-2-yl)guanidine potassium chloride SB 699551 A SB-699551-A serotonin 5 receptor serotonin antagonist serotonin receptor thiazole derivative animal experiment article auditory stimulation behavior brain electrophysiology chloride conductance controlled study evoked auditory response excitatory postsynaptic potential goldfish Mauthner cell nerve cell excitability nerve cell membrane steady potential nerve cell plasticity nonhuman prepulse inhibition priority journal sensory gating startle reflex swimming acoustics animal cytology dose response drug effect electrostimulation evoked auditory response female inhibitory postsynaptic potential male metabolism methodology nerve cell nerve cell inhibition nerve cell network nerve tract patch clamp physiology sensory gating spinal cord time Acoustic Stimulation Acoustics Animals Biphenyl Compounds Dose-Response Relationship, Drug Electric Stimulation Evoked Potentials, Auditory Excitatory Postsynaptic Potentials Female Goldfish Guanidines Inhibitory Postsynaptic Potentials Male Nerve Net Neural Inhibition Neural Pathways Neurons Patch-Clamp Techniques Potassium Chloride Receptors, Serotonin Sensory Gating Serotonin Antagonists Spinal Cord Startle Reaction Thiazoles Time Factors Curtin, P.C.P. Medan, V. Neumeister, H. Bronson, D.R. Preuss, T. The 5-HT5A receptor regulates excitability in the auditory startle circuit: Functional implications for sensorimotor gating |
| topic_facet |
serotonin 5A receptor serotonin antagonist biphenyl derivative guanidine derivative N (2,6 dimethoxybenzyl) N' (4 (4 fluorophenyl)thiazol 2 yl)guanidine N-(2,6-dimethoxybenzyl)-N'-(4-(4-fluorophenyl)thiazol-2-yl)guanidine potassium chloride SB 699551 A SB-699551-A serotonin 5 receptor serotonin antagonist serotonin receptor thiazole derivative animal experiment article auditory stimulation behavior brain electrophysiology chloride conductance controlled study evoked auditory response excitatory postsynaptic potential goldfish Mauthner cell nerve cell excitability nerve cell membrane steady potential nerve cell plasticity nonhuman prepulse inhibition priority journal sensory gating startle reflex swimming acoustics animal cytology dose response drug effect electrostimulation evoked auditory response female inhibitory postsynaptic potential male metabolism methodology nerve cell nerve cell inhibition nerve cell network nerve tract patch clamp physiology sensory gating spinal cord time Acoustic Stimulation Acoustics Animals Biphenyl Compounds Dose-Response Relationship, Drug Electric Stimulation Evoked Potentials, Auditory Excitatory Postsynaptic Potentials Female Goldfish Guanidines Inhibitory Postsynaptic Potentials Male Nerve Net Neural Inhibition Neural Pathways Neurons Patch-Clamp Techniques Potassium Chloride Receptors, Serotonin Sensory Gating Serotonin Antagonists Spinal Cord Startle Reaction Thiazoles Time Factors |
| description |
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. © 2013 the authors. |
| format |
JOUR |
| author |
Curtin, P.C.P. Medan, V. Neumeister, H. Bronson, D.R. Preuss, T. |
| author_facet |
Curtin, P.C.P. Medan, V. Neumeister, H. Bronson, D.R. Preuss, T. |
| author_sort |
Curtin, P.C.P. |
| title |
The 5-HT5A receptor regulates excitability in the auditory startle circuit: Functional implications for sensorimotor gating |
| title_short |
The 5-HT5A receptor regulates excitability in the auditory startle circuit: Functional implications for sensorimotor gating |
| title_full |
The 5-HT5A receptor regulates excitability in the auditory startle circuit: Functional implications for sensorimotor gating |
| title_fullStr |
The 5-HT5A receptor regulates excitability in the auditory startle circuit: Functional implications for sensorimotor gating |
| title_full_unstemmed |
The 5-HT5A receptor regulates excitability in the auditory startle circuit: Functional implications for sensorimotor gating |
| title_sort |
5-ht5a receptor regulates excitability in the auditory startle circuit: functional implications for sensorimotor gating |
| url |
http://hdl.handle.net/20.500.12110/paper_02706474_v33_n24_p10011_Curtin |
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