Increase of oscillatory inhibitory synaptic events in thalamic relay neurons after inhibition of NMDA-mediated transmission-760.24

SERULLE Y, URBANO FJ, LISMAN JE, LLINAS RR

Washington DC

Congreso; 38th Society for Neuroscience Meeting; 2008

Society for Neuroscience

Thalamocortical activity is the product of the intrinsic properties of thalamic neurons, their recurrent connectivity with the cortex and the synaptic input from sensory and mesencephalic neurons. Abnormal thalamocortical rhythms play an important role in the pathophysiology of different neuropsychiatric diseases, including Parkinson’s disease, schizophrenia, neurogenic pain and tinnitus. In fact, it has been established that compared to controls, patients suffering from the above-mentioned disorders exhibit an increase in low-frequency (theta) rhythmicity. Low-frequency oscillatory activity is sustained by the activity of T-type calcium channels, which are activated at membrane voltages negative to resting potentials. Recent work (see Zhang and Lisman, and Yu et al., this meeting) indicates that NMDA antagonists, which are known to reproduce many aspects of schizophrenia, can hyperpolarize cells of the nucleus reticularis and induce bursting. To study the consequences for thalamic relay cells, we obtained patch-clamp recordings from ventrobasal thalamic relay neurons in vitro. Application of APV in the thalamocortical slice induced a hyperpolarization of thalamic relay neurons. Voltage- and current-clamp experiments showed that application of APV and CNQX increased the frequency of both spontaneous inhibitory postsynaptic currents (IPSCs) and potentials (IPSPs) in ventrobasal neurons, most likely generated by thalamic reticular neurons burst firing. Moreover, the frequency at which these inhibitory events occur is in accordance with the frequency at which reticular thalamic neurons oscillate, suggesting that in the absence of cortical input, the intrinsic properties of thalamic reticular neurons may regulate the activity of thalamic relay neurons. Current clamp experiments further indicate that the oscillatory inhibitory input results in oscillatory thalamic burst activity. Such bursting may establish a recurrent thalamocortical dysrhythmia. Observation of this dysrhythmia in vitro opens the door for its biophysical analysis and the identification of pharmacological agents that can abolish it. NIH-NINDS-NS13742-30