title: Hearing loss alters serotonergic modulation of intrinsic excitability in auditory cortex.
abstract: Sensorineural hearing loss during early childhood alters auditory cortical evoked potentials in humans and profoundly changes auditory processing in hearing-impaired animals. Multiple mechanisms underlie the early postnatal establishment of cortical circuits, but one important set of developmental mechanisms relies on the neuromodulator serotonin (5-hydroxytryptamine [5-HT]). On the other hand, early sensory activity may also regulate the establishment of adultlike 5-HT receptor expression and function. We examined the role of 5-HT in auditory cortex by first investigating how 5-HT neurotransmission and 5-HT(2) receptors influence the intrinsic excitability of layer II/III pyramidal neurons in brain slices of primary auditory cortex (A1). A brief application of 5-HT (50 μM) transiently and reversibly decreased firing rates, input resistance, and spike rate adaptation in normal postnatal day 12 (P12) to P21 rats. Compared with sham-operated animals, cochlear ablation increased excitability at P12-P21, but all the effects of 5-HT, except for the decrease in adaptation, were eliminated in both sham-operated and cochlear-ablated rats. At P30-P35, cochlear ablation did not increase intrinsic excitability compared with shams, but it did prevent a pronounced decrease in excitability that appeared 10 min after 5-HT application. We also tested whether the effects on excitability were mediated by 5-HT(2) receptors. In the presence of the 5-HT(2)-receptor antagonist, ketanserin, 5-HT significantly decreased excitability compared with 5-HT or ketanserin alone in both sham-operated and cochlear-ablated P12-P21 rats. However, at P30-P35, ketanserin had no effect in sham-operated and only a modest effect cochlear-ablated animals. The 5-HT(2)-specific agonist 5-methoxy-N,N-dimethyltryptamine also had no effect at P12-P21. These results suggest that 5-HT likely regulates pyramidal cell excitability via multiple receptor subtypes with opposing effects. These data also show that early sensorineural hearing loss affects the ability of 5-HT receptor activation to modulate A1 pyramidal cell excitability.
authors.affiliation: Department of Cell and Molecular Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Deepti
authors.initials: D
authors.lastname: Rao
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Basura
authors.forename: Joseph
authors.initials: J
authors.lastname: Roche
authors.forename: Scott
authors.initials: S
authors.lastname: Daniels
authors.forename: Jaime G
authors.initials: JG
authors.lastname: Mancilla
authors.forename: Paul B
authors.initials: PB
authors.lastname: Manis
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001303:Auditory Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D004594:Electrophysiology; D034381:Hearing Loss / Q000378:metabolism / Q000503:physiopathology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D044348:Receptors, Serotonin, 5-HT2; D012701:Serotonin