Selective upregulation of T alpha 1 alpha-tubulin and neuropeptide Y mRNAs after intermittent excitatory stimulation in adult rat hippocampus in vivo.

Abstract

Adult central neurons exhibit significant structural and molecular changes in epilepsy. We have examined changes in two markers of morphological and physiological plasticity, T alpha 1 alpha-tubulin (T alpha 1) and neuropeptide Y (NPY) mRNAs, in response to intermittent (20 Hz, 10 seconds, 1 minute-1) stimulation of the rat perforant path in vivo. Stimulus trains elicited brief (0.5-3 seconds) afterdischarges in the ipsilateral dentate gyrus (DG). Four hours of stimulation caused no significant loss of inhibition in the DG 40-48 hours after stimulation ceased. However, it did lead to an increase in NPY mRNA in neurons of the ipsilateral and, to a lesser extent, contralateral DGs and Ammon's Horn. Many of these were presumably interneurons that normally express NPY. However, dentate granule cells (DGCs), which do not normally express this peptide, also expressed robust levels of NPY mRNA bilaterally. NPY mRNA levels peaked at 4-24 hours and returned to baseline by 48 hours poststimulation. Although 24 hours of stimulation induced a similar increase in interneurons, DGCs showed no detectable NPY mRNA. Afterdischarges were necessary to elevate NPY mRNA expression. Four hours of stimulation elevated T alpha 1 mRNA expression in both ipsilateral and, to a lesser extent, contralateral DGCs; this elevation peaked at 24 hours poststimulation and declined to baseline by 72 hours. Stimulation for 24 hours caused broader changes in T alpha 1 mRNA expression, with increases in DGCs and in CA3 pyramidal cells bilaterally. Acute denervation of the DG did not affect T alpha 1 mRNA level in the hippocampal formation. Elevated synaptic input resulting in afterdischarges, but not necessarily in excitability changes in the DG, led to alterations in the expression of molecular markers of plasticity. These changes may reflect adaptive responses to physiological activation.