Humans who have suffered from periods of hearing loss during development can experience permanent debilitating impairments in sound and language perception! These impairments include deficits in spectrotemporal processing. Inhibitory circuits in the auditory cortex are vulnerable to hearing loss and may be critical for spectrotemporal processing. Specifically, inhibitory transmission displays short-term plasticity which may contribute to the encoding of temporal patterns of acoustic stimuli. My preliminary data suggests that inhibitory short-term plasticity is altered by deafness. The objective of this application is to study how deafness may impact normal development of inhibitory short-term plasticity and how these changes may alter efficacy and timing of auditory cortex discharge patterns. A series of whole-cell experiments in neurons of the'auditory cortex are specifically designed to characterize (1) the normal development of inhibitory short-term plasticity (2) the impact of deafness on inhibitory short- term plasticity (3) the effects of inhibitory short-term plasticity on discharge properties. To characterize development of inhibitory short-term plasticity in normal and deaf animals, paired and multiple-pulse stimuli will be used to evoke trains of inhibitory synaptic events. Pharmacological manipulations, particularly targeting pre and postsynaptic GABAB receptors, will be used to uncover the mechanisms underlying normal developmental short-term plasticity and the changes following deafness. Finally, to understand the functional consequences of these changes, the effects of inhibitory short-term plasticity on spike efficacy and timing will be evaluated by integrating synaptic inhibition with neuronal spiking. Relevance: These experiments will assess whether changes in temporal responses of inhibitory synapses may partially explain auditory processing deficits following hearing loss, including impairments in speech production and perception. Particularly due to pur extensive knowledge of GABAB receptor pharmacology, revealing the involvement of these receptors in temporal responses will broaden our strategies to prevent and alleviate behavioral deficits associated with hearing loss. ? ? ?
| Takesian, Anne E; Kotak, Vibhakar C; Sharma, Neeti et al. (2013) Hearing loss differentially affects thalamic drive to two cortical interneuron subtypes. J Neurophysiol 110:999-1008 |
| Takesian, Anne E; Kotak, Vibhakar C; Sanes, Dan H (2012) Age-dependent effect of hearing loss on cortical inhibitory synapse function. J Neurophysiol 107:937-47 |
| Takesian, Anne E; Kotak, Vibhakar C; Sanes, Dan H (2010) Presynaptic GABA(B) receptors regulate experience-dependent development of inhibitory short-term plasticity. J Neurosci 30:2716-27 |
| Takesian, Anne E; Kotak, Vibhakar C; Sanes, Dan H (2009) Developmental hearing loss disrupts synaptic inhibition: implications for auditory processing. Future Neurol 4:331-349 |
