We examined electrophysiological and molecular changes of the thalamocortical system after thalamic degeneration in Purkinje cell degeneration (pcd) mice. In pcd mice, neurons in specific thalamic nuclei including the ventral medial geniculate nucleus began to degenerate around postnatal day 50, whereas the visual thalamic nucleus and nonspecific thalamic nuclei remained almost intact. In association with the morphological changes, auditory evoked potentials in the primary auditory cortex (AC) began to decrease gradually. Fast Fourier transform analysis of spontaneous cortical field potentials revealed that fast oscillation (FO) around 25 Hz occurred in the AC but not in the visual cortex. Quantitative mRNA analysis demonstrated that expression of the N-methyl-D-aspartate (NMDA) receptor was up-regulated in the AC but not in the visual cortex. Systemic administration of an NMDA antagonist abolished the FO in the AC. These results indicate that increased NMDA activity may cause the FO in the AC of pcd mice. (c) 2007 Elsevier Inc. All rights reserved.