It is well established that learning and experience lead to auditory cortical plasticity that is highly specific to the frequency of the acquired sound. Frequency specificity is demonstrated as the shift in the receptive field of cortical neurons towards the frequency of the acquired sound. Jafari and others showed that this frequency-specific receptive field shift of cortical neurons can be induced by focal electrical stimulation of the ventral division of the medial geniculate body (MGBv) of the thalamus; implicating that, auditory thalamocortical system is important for frequency-specific receptive field plasticity. Up and down regulation of synaptic strength, i.e. long-term potentiation (LTP) and long-term depression (LTD) of thalamocortical synaptic transmission is proposed as an underlying mechanism for such cortical plasticity. To date, auditory thalamocortical synaptic plasticity and its relation to frequency specific plasticity remain poorly characterized. The present thesis illustrates the changes in thalamocortical field postsynaptic excitatory potential (fEPSP) in the primary auditory cortex (AI) by high frequency tetanic stimulation of the MGBv (TSMGBv). Anesthetized mice were employed as the experimental model. The thesis is divided into three research projects. The first one was to characterize the changes in thalamocortical fEPSP following TSMGBv. I found that TSMGBv induced significant depression in thalamocortical fEPSP at the best frequency (BF) of the recorded AI neurons (BFAI) and potentiation at the BF of stimulated MGBv (BFMGBv) neurons. The depression and potentiation were based on the analysis of the fEPSP amplitude, latency and rising slope. It should be noted here that the BFs of all studied AI neurons were different from those of stimulated MGBv neurons. The second project was to test the role of NMDA and GABAA receptors in TSMGBv-induced changes in thalamocortical fEPSPs. Microiontophoresis application of d-(-)-2-amino-5-phosphonovalerate (APV), a NMDAR antagonists and Bicuculline methiodide (BMI), a GABAA antagonists using multibarrel electrode was given to the recorded loci in the AI. I found that, under continuous application of APV to the recorded AI neurons, TSMGBv led to significant decrease in the cortical fEPSPs at both BFAI and BFMGBv. The decrease in fEPSP at the BFAI was significantly greater than that without APV application. Next, I found that under the continuous application of BMI, TSMGBv induced LTP at both BFAI and BFMGBv. The LTP at BFMGBv was significantly larger than that without BMI application. When APV and BMI were applied simultaneously, TSMGBv did not change the thalamocortical fEPSP. These findings suggest that NMDA receptors play an important role in the TSMGBv-induced thalamocortical LTP/LTD and that cortical inhibition must be involved in TSMGBv-induced thalamocortical LTP/LTD.
Since ketamine is known to be a non-competitive NMDAR antagonist, the third project was to assess the impact of ketamine on thalamocortical plasticity. I compared the effects of ketamine and urethane on the extent of thalamocortical LTP/LTD after TSMGBv. I found that TSMGBv-induced changes in the thalamocortical fEPSPs were similar under both anaesthetic conditions. In conclusion, the results presented in this thesis demonstrate that the fEPSPs of the inputs from tetanized MGBv neurons are potentiated whereas those from non-tetanized MGBv neurons are depressed. The TSMGBv-induced LTP is mediated by NMDA receptors and LTD by GABAA receptors. Finally, my data further confirm that the NMDA-antagonist effects of ketamine have minor impact on the study of cortical plasticity as reported by others.