The effects of transcriptional inhibition on spatial learning and density of receptors in rat hippocampus

Abstract

The investigation of learning and memory has focused considerable attention on LTP as a possible cellular mechanism responsible for consolidation. Several studies have provided evidence that inhibition of the activity of proteins involved in LTP has a detrimental affect on consolidation. In addition to the behavioral studies, considerable evidence has been gathered to determine the cellular mechanisms responsible for LTP. Of specific interest to the current study was the effect produced following the administration of a transcriptional inhibitor, which resulted in the ablation of the late phase of LTP. In the current study, Sprague-Dawley rats were given an infusion (50μM and 25μM) of a transcriptional inhibitor (Actinomycin D) directly into the CA1 field of the hippocampus. Following the infusion, rats were tested in a Morris water maze to determine if transcriptional inhibition caused any decrements in the acquisition of the spatial task. The results indicated that the drug did disrupt subjects' performance compared to saline controls. The data gathered suggested that the difference between treatment groups was in the precision of localizing the platform in the target quadrant, not in the subjects' ability to locate the platform quadrant. No differences in swim speed or ability to locate a cued platform were observed. It has been suggested that one of the cellular alterations responsible for LTP is an upregulation in the receptors responsible for the responsive properties of the postsynaptic neuron. The current study also examined differences in the densities of AMPA and NMDA receptor binding in CA1 following inhibition of transcription. In addition, the relative densities of the mRNA precursors for those receptors were examined. The results from the current study indicated that the administration of the transcriptional inhibitor to the CA1 field of the hippocampus altered the density of binding to both AMPA and NMDA receptors. The administration of the drug did not reliably affect the expression of mRNA for several subunits of glutamate receptors expressed in the CA1 field of the hippocampus.