Role of serotonin in auditory cortex regulation following early-onset sensorineur

The mammalian cerebral cortex is one of the most complex information processing systems known. Although
cortical neurons exhibit a variety of intrinsic electrical properties, which are critical for function, it is the synaptic
interactions between cells, afferent neurotransmitter systems and the organization of local circuits that play the
most critical roles in cortical computation and function. Within the auditory system, the cortex stands in
contrast to the medullary and midbrain auditory structures which, although performing significant processing,
rely more heavily on the intrinsic electrical properties of neurons embedded in a relatively fixed circuit. Hearing
impairments during early postnatal development produce significant changes in the human auditory cortex that
may permanently diminish auditory perceptual skills and compromise language acquisition (Psarommatis et al.,
2001; Kidd et al., 2002; Emmorey et al., 2003). These affects are particularly severe in children who are born
with or who develop an early pre-lingual sensorineural hearing loss; producing long periods of auditory
deprivation (Sharma et al., 2002). Profound changes in auditory processing have been observed in hearing-
impaired animals (Syka, 2002), and recent data have shown that bilateral cochlear ablation produces
heightened excitability of primary auditory (A1) cortical neurons in postnatal rodents (Kotak et al., 2005),
suggesting that this experimental paradigm may be useful to investigate mechanisms underlying early
sensorineural hearing loss (SNHL). Preliminary studies from our laboratory have investigated the contribution
of serotonin (5-hydroxytryptamine; 5-HT), mediated by 5-HT2 receptors, to A1 neuronal excitability in this
rodent model of SNHL. In this proposal, we have designed two specific AIMS to test the hypothesis that
cochlear ablation, as a model of early onset SNHL, alters the 5-HT2 receptor-linkage of A1 pyramidal cell
function and induces compensatory plasticity within the serotonergic system.