Changes in Membrane and Synaptic Properties of Thalamocortical Circuitry Caused by Hydrogen Peroxide

Abstract

Frantseva, Marina V., Jose L. Perez Velazquez, and Peter L. Carlen. Changes in membrane and synaptic properties of thalamocortical circuitry caused by hydrogen peroxide. J. Neurophysiol. 80: 1317–1326, 1998. Free radical (FR) production was linked to the generation of epileptiform activity. We performed electrophysiological recordings in rat thalamocortical slices to investigate the effects of FRs on the intrinsic and synaptic properties of thalamic and cortical neurons. Whole cell recordings from identified cortical pyramidal neurons and thalamic neurons of the ventrobasal nucleus revealed that exposure to the FR-forming agent H2O2 (2.5 mM) decreased γ-aminobutyric acid-A– and γ-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 application increased excitatory transmission in thalamic neurons to 162.9 ± 29.6% of control but caused no change in cortical neurons. H2O2 altered significantly the characteristic low-pass filter behavior of 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 frequencies 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 extracellular 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 hyperexcitability. These observations indicate that FRs could promote hyperexcitability of thalamocortical circuits by altering the balance between excitation and inhibition and by transforming the characteristic low-pass filter behavior into a flat band-pass filter.