COMPUTER-MODEL OF CLONAZEPAMS EFFECT IN THALAMIC SLICE

IN the thalamus, paradoxical changes in response to augmentation of in hibition can occur as a result of either cellular or network effects. Clonazepam, a GABA(A) agonist, produces a paradoxical reduction in evo ked thalamocortical neuron inhibitory postsynaptic potential (IPSP) in thalamic slice. This has been hypothesized to be a result of augmenta tion in inhibitory to inhibitory connections. In a computer model, ort hodromic simulation produced an increase in initial IPSP, a result con trary to that found experimentally. This failure was traced to the ina bility of orthodromic activation to produce fast enough recurrent inhi bition to alter initial reticularis neuron firing. Simulated antidromi c stimulation was able to reduce this initial spike train and reproduc ed the experimental finding.