Plasticity of the Rat Thalamocortical Auditory System During Development and Following White Noise Exposure
Hogsden Robinson, Jennifer Lauren
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Synaptic plasticity reflects the capacity of synapses to undergo changes in synaptic strength and connectivity, and is highly regulated by age and sensory experience. This thesis focuses on the characterization of synaptic plasticity in the primary auditory cortex (A1) of rats throughout development and following sensory deprivation. Initial experiments revealed an age-dependent decline in plasticity, as indicated by reductions in long-term potentiation (LTP). The enhanced plasticity of juvenile rats appeared to be mediated by NR2B subunits of the N-methyl-d-aspartate receptor (NMDAR), as NR2B antagonist application reduced LTP to adult-like levels in juveniles, yet had no effect in adults. The importance of sensory experience in mediating plasticity was revealed in experiments using white noise exposure, which is a sensory deprivation technique known to arrest cortical development in A1. Notably, adult rats reared in continuous white noise maintained more juvenile-like levels of LTP, which normalized upon subsequent exposure to an unaltered acoustic environment. The white noise-induced LTP enhancements also appeared to be mediated by NR2B subunits, as NR2B antagonists reversed these LTP enhancements in white noise-reared rats. Given the strong influence that sensory experience exerts on plasticity, additional experiments examined the effect of shorter episodes of white noise exposure on LTP in adult rats. Exposure to white noise during early postnatal life appeared to “prime” A1 for subsequent exposure in adulthood, resulting in enhanced LTP. The necessity of early-life exposure was evident, as repeated episodes of white noise in adulthood did not enhance plasticity. In older rats that typically no longer express LTP in A1, pharmacological methods to enhance plasticity were explored. Moderate LTP was observed in older rats with cortical zinc application, which may act through its antagonism of NR2A subunits of the NMDAR. Additionally, current source density and cortical silencing analyses were conducted to characterize the distinct peaks of field postsynaptic potentials recorded in A1, with the earlier and later peaks likely representing thalamocortical and intracortical synapses, respectively. Together, this thesis emphasizes the critical role of sensory experience in determining levels of cortical plasticity, and demonstrates strategies to enhance plasticity in the mature auditory cortex.