CHANGES IN MEMBRANE AND SYNAPTIC PROPERTIES OF THALAMOCORTICAL CIRCUITRY CAUSED BY HYDROGEN-PEROXIDE

Free radical(FR) production was linked to the generation of epileptifo rm activity. We performed electrophysiological recordings in rat thala mocortical slices to investigate the effects of FRs on the intrinsic a nd synaptic properties of thalamic and cortical neurons. Whole cell re cordings from identified cortical pyramidal neurons and thalamic neuro ns of the ventrobasal nucleus revealed that exposure to the FR-forming agent H2O2 (2.5 mb/I) decreased gamma-aminobutyric acid-A- and gamma- aminobutyric acid-B-mediated inhibition to 35.3 +/- 13.4% and 13.7 +/- 4.4% (means +/- SE) of control in cortical neurons and to 41.8 +/- 14 .8% and 33.6 +/- 11.6% of control in thalamic neurons. H2O2 applicatio n increased excitatory transmission in thalamic neurons to 162.9 +/- 2 9.6% of control but caused no change in cortical neurons. H2O2 altered significantly the characteristic low-pass filter behavior or cortical and thalamic cells as determined by their input impedances. After 35 min of superfusion, the impedance of cortical neurons decreased by 67. 0 +/- 14.5%, and thalamic decreased by 76.3 +/- 2.7% for the frequenci es in the range 1-50 Hz while remaining constant for frequencies >200 Hz. Neuronal hyperexcitability was manifested during H2O2 exposure by continuous firing and long depolarizing shifts in response to extracel lular stimulation in both thalamocortical and cortical neurons only in slices preserving thalamocortical connections. In slices with severed thalamocortical connections, cortical neurons did not show signs of h yperexcitability. These observations indicate that FRs could promote h yperexcitability of thalamocortical circuits by altering the balance b etween excitation and inhibition and by transforming the characteristi c lowpass filter behavior into a flat band-pass filter.