RECOVERY OF HIPPOCAMPAL DENTATE GRANULE CELL RESPONSIVENESS TO ENTORHINAL CORTICAL INPUT FOLLOWING NOREPINEPHRINE DEPLETION

Hippocampal dentate granule cell responsivity to excitatory input from entorhinal perforant path fibers was examined in the chronic rabbit p reparation following norepinephrine (NE) depletion induced with the ne urotoxin DSP4. To examine granule cell responsivity as a function of p erforant path activation, constant low frequency stimulation (0.1 Hz) was applied to the perforant path using an ascending intensity series. To examine granule cell responsivity to more complex patterns of stim ulation, a train of impulses, with a random interstimulus interval (Po isson distribution; mean frequency of 2 Hz), was applied to the perfor ant path. Both single impulse and random interval impulse stimulation revealed that NE depletion increased the average amplitude of the perf orant path-granule cell population spike. The random interval impulse stimulation revealed that NE depletion also increased the magnitude an d duration of second order inhibitory interactions. These changes were transient, however, and recovered over the 21 day test period. Hippoc ampal NE levels were reduced an average of 80% between 23 and 38 days post-DSP4. The activity of the rate-limiting enzyme for NE synthesis, tyrosine hydroxylase (TH), was reduced an average of 60%. That NE leve ls were reduced to a greater extent than was TH activity is suggestive of increased NE synthesis within the remaining nerve terminals. Such an increase in NE synthesis may reflect a compensatory response underl ying the functional recovery of electrophysiological responsiveness fo llowing partial NE depletion.