Hearing loss alters serotonergic modulation of intrinsic excitability in auditory cortex.

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.

[1]  U. Spampinato,et al.  Transient expression of 5-HT1A receptor binding sites in some areas of the rat CNS during postnatal development , 1987, International Journal of Developmental Neuroscience.

[2]  P. Carlen,et al.  Serotonin agonist and antagonist actions in hippocampal CA1 neurons. , 1990, Canadian journal of physiology and pharmacology.

[3]  K. Svoboda,et al.  Development of intrinsic properties and excitability of layer 2/3 pyramidal neurons during a critical period for sensory maps in rat barrel cortex. , 2004, Journal of neurophysiology.

[4]  S. Bao,et al.  Tuning up the developing auditory CNS , 2009, Current Opinion in Neurobiology.

[5]  John G. Parnavelas,et al.  The Role of Serotonin in Early Cortical Development , 2003, Developmental Neuroscience.

[6]  J. Lauder.  Ontogeny of the Serotonergic System in the Rat: Serotonin as a Developmental Signal a , 1990, Annals of the New York Academy of Sciences.

[7]  R. Ilmoniemi,et al.  Auditory selective attention modulated by tryptophan depletion in humans , 2003, Neuroscience Letters.

[8]  Yasuhiro R. Tanaka,et al.  The effects of cutting solutions on the viability of GABAergic interneurons in cerebral cortical slices of adult mice , 2008, Journal of Neuroscience Methods.

[9]  B. Roth,et al.  Differential modes of agonist binding to 5-hydroxytryptamine(2A) serotonin receptors revealed by mutation and molecular modeling of conserved residues in transmembrane region 5. , 2000, Molecular pharmacology.

[10]  S. Foote,et al.  Distribution of choline acetyltransferase‐, serotonin‐, dopamine‐β‐hydroxylase‐, tyrosine hydroxylase‐immunoreactive fibers in monkey primary auditory cortex , 1987, The Journal of comparative neurology.

[11]  Dan H. Sanes,et al.  Conductive Hearing Loss Disrupts Synaptic and Spike Adaptation in Developing Auditory Cortex , 2007, The Journal of Neuroscience.

[12]  C. Schreiner,et al.  Development of spectral and temporal response selectivity in the auditory cortex. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Hanna Damasio,et al.  A morphometric analysis of auditory brain regions in congenitally deaf adults , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[14]  A. Erisir,et al.  Function of specific K(+) channels in sustained high-frequency firing of fast-spiking neocortical interneurons. , 1999, Journal of neurophysiology.

[15]  Thomas Dierks,et al.  Intensity dependence of auditory evoked potentials (AEPs) as biological marker for cerebral serotonin levels: effects of tryptophan depletion in healthy subjects , 1999, Psychopharmacology.

[16]  Georg Juckel,et al.  Intensity dependence of auditory evoked potentials as an indicator of central serotonergic neurotransmission: A new hypothesis , 1993, Biological Psychiatry.

[17]  C. Schreiner,et al.  Sensory input directs spatial and temporal plasticity in primary auditory cortex. , 2001, Journal of neurophysiology.

[18]  Zhong-wei Zhang.  Serotonin Induces Tonic Firing in Layer V Pyramidal Neurons of Rat Prefrontal Cortex during Postnatal Development , 2003, The Journal of Neuroscience.

[19]  B. Roth,et al.  Control of Serotonergic Function in Medial Prefrontal Cortex by Serotonin-2A Receptors through a Glutamate-Dependent Mechanism , 2001, The Journal of Neuroscience.

[20]  Andrej Kral,et al.  Unimodal and cross-modal plasticity in the ‘deaf’ auditory cortex , 2007, International journal of audiology.

[21]  R. North,et al.  Actions of 5-hydroxytryptamine on neurons of the rat cingulate cortex. , 1993, Journal of neurophysiology.

[22]  R. Andrade,et al.  A 5-HT7 Receptor-Mediated Depolarization in the Anterodorsal Thalamus. II. Involvement of the Hyperpolarization-Activated Current Ih , 2001 .

[23]  J. Bakin,et al.  Induction of a physiological memory in the cerebral cortex by stimulation of the nucleus basalis. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[24]  N. Suga,et al.  Serotonergic Modulation of Plasticity of the Auditory Cortex Elicited by Fear Conditioning , 2007, The Journal of Neuroscience.

[25]  M. Merzenich,et al.  Cortical remodelling induced by activity of ventral tegmental dopamine neurons , 2001, Nature.

[26]  Dan H. Sanes,et al.  Hearing Loss Prevents the Maturation of GABAergic Transmission in the Auditory Cortex , 2008, Cerebral cortex.

[27]  I. Psarommatis,et al.  Hearing loss in speech-language delayed children. , 2001, International journal of pediatric otorhinolaryngology.

[28]  H. Francis,et al.  Effects of deafferentation on the electrophysiology of ventral cochlear nucleus neurons , 2000, Hearing Research.

[29]  R. Andrade,et al.  5-Hydroxytryptamine2 and 5-hydroxytryptamine1A receptors mediate opposing responses on membrane excitability in rat association cortex , 1991, Neuroscience.

[30]  A. Lalwani,et al.  The use of Preyer's reflex in evaluation of hearing in mice. , 2001, Acta oto-laryngologica.

[31]  B. Glenthøj,et al.  Divergent effects of increased serotonergic activity on psychophysiological parameters of human attention. , 2008, The international journal of neuropsychopharmacology.

[32]  Paul Chen,et al.  Activation of 5-HT2A/C Receptors Counteracts 5-HT1A Regulation of N-Methyl-D-aspartate Receptor Channels in Pyramidal Neurons of Prefrontal Cortex , 2008, Journal of Biological Chemistry.

[33]  Christian Lüscher,et al.  G Protein-Coupled Inwardly Rectifying K+ Channels (GIRKs) Mediate Postsynaptic but Not Presynaptic Transmitter Actions in Hippocampal Neurons , 1997, Neuron.

[34]  Edward F Chang,et al.  Environmental Noise Retards Auditory Cortical Development , 2003, Science.

[35]  A. Alonso,et al.  Effects of serotonin on the intrinsic membrane properties of layer II medial entorhinal cortex neurons , 2007, Hippocampus.

[36]  L. Krubitzer,et al.  Multisensory plasticity in congenitally deaf mice: How are cortical areas functionally specified? , 2006, Neuroscience.

[37]  Efrain C Azmitia,et al.  Modern views on an ancient chemical: serotonin effects on cell proliferation, maturation, and apoptosis , 2001, Brain Research Bulletin.

[38]  M. Hamon,et al.  Postnatal development and localization of 5-HT1A receptor mRNA in rat forebrain and cerebellum. , 1994, Brain research. Developmental brain research.

[39]  R. Nicoll,et al.  Pharmacologically distinct actions of serotonin on single pyramidal neurones of the rat hippocampus recorded in vitro. , 1987, The Journal of physiology.

[40]  R. Andrade,et al.  Serotonergic Regulation of Membrane Potential in Developing Rat Prefrontal Cortex: Coordinated Expression of 5-Hydroxytryptamine (5-HT)1A, 5-HT2A, and 5-HT7 Receptors , 2004, The Journal of Neuroscience.

[41]  Daniel Hoyer,et al.  Molecular, pharmacological and functional diversity of 5-HT receptors , 2002, Pharmacology Biochemistry and Behavior.

[42]  Robert K Shepherd,et al.  Cochlear implants stimulate activity-dependent CREB pathway in the deaf auditory cortex: implications for molecular plasticity induced by neural prosthetic devices. , 2008, Cerebral cortex.

[43]  S. Nelson,et al.  Selective reconfiguration of layer 4 visual cortical circuitry by visual deprivation , 2004, Nature Neuroscience.

[44]  Sujay K. Singh,et al.  Expression of 5-HT2A, 5-HT2B and 5-HT2C receptors in the mouse embryo , 2000, International Journal of Developmental Neuroscience.

[45]  Shihab A. Shamma,et al.  Auditory cortex , 1998 .

[46]  Donata Oertel,et al.  Bidirectional synaptic plasticity in the cerebellum-like mammalian dorsal cochlear nucleus , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[47]  Li I. Zhang,et al.  Persistent and specific influences of early acoustic environments on primary auditory cortex , 2001, Nature Neuroscience.

[48]  Jyrki Ahveninen,et al.  Serotonin Modulates Early Cortical Auditory Processing in Healthy Subjects. Evidence from MEG with Acute Tryptophan Depletion , 2002, Neuropsychopharmacology.

[49]  H. Haas,et al.  5-HT inhibits lateral entorhinal cortical neurons of the rat in vitro by activation of potassium channel-coupled 5-HT1A receptors , 1997, Brain Research.

[50]  Dan H. Sanes,et al.  Hearing Loss Raises Excitability in the Auditory Cortex , 2005, The Journal of Neuroscience.

[51]  R. Andrade,et al.  5-Hydroxytryptamine4-like receptors mediate the slow excitatory response to serotonin in the rat hippocampus. , 1991, The Journal of pharmacology and experimental therapeutics.

[52]  S. Heinemann,et al.  Embryonic Expression of the 5-HT3 Receptor Subunit, 5-HT3R-A, in the Rat: An in Situ Hybridization Study , 1995, Molecular and Cellular Neuroscience.

[53]  G. Karmos,et al.  Auditory-evoked potentials as indicator of brain serotonergic activity first evidence in behaving cats , 1997, Biological Psychiatry.

[54]  J. Ahveninen,et al.  Acute trytophan depletion decreases intensity dependence of auditory evoked magnetic N1/P2 dipole source activity , 2002, Psychopharmacology.

[55]  S. Cruikshank,et al.  Thalamocortical inputs trigger a propagating envelope of gamma-band activity in auditory cortex in vitro , 1999, Experimental Brain Research.

[56]  Paul B. Manis,et al.  Ontogeny of serotonin and serotonin2A receptors in rat auditory cortex , 2008, Hearing Research.

[57]  Christine R. Mason,et al.  Informational Masking in Listeners with Sensorineural Hearing Loss , 2002, Journal of the Association for Research in Otolaryngology.

[58]  R. Foehring,et al.  The ontogeny of repetitive firing and its modulation by norepinephrine in rat neocortical neurons. , 1993, Brain research. Developmental brain research.

[59]  D. Prince,et al.  Two distinct effects of 5-hydroxytryptamine on single cortical neurons , 1987, Brain Research.

[60]  S. Cruikshank,et al.  Auditory thalamocortical synaptic transmission in vitro. , 2002, Journal of neurophysiology.

[61]  Niraj S. Desai,et al.  Plasticity in the intrinsic excitability of cortical pyramidal neurons , 1999, Nature Neuroscience.

[62]  Paul B. Manis,et al.  Temporal Coding by Cochlear Nucleus Bushy Cells in DBA/2J Mice with Early Onset Hearing Loss , 2006, Journal of the Association for Research in Otolaryngology.

[63]  M. Kilgard,et al.  Cortical map reorganization enabled by nucleus basalis activity. , 1998, Science.

[64]  E. Chang,et al.  Critical Period Window for Spectral Tuning Defined in the Primary Auditory Cortex (A1) in the Rat , 2007, The Journal of Neuroscience.

[65]  Anne-Marie M Oswald,et al.  Maturation of intrinsic and synaptic properties of layer 2/3 pyramidal neurons in mouse auditory cortex. , 2008, Journal of neurophysiology.