Role of norepinephrine in the hippocampal CA 1 region of the rat : inhibition and disinhibition

The effect of norepinephrine (NE) perfusion on electrophysiological activities of the CA1 region evoked by stratum radiatum stimulation were examined in the rat hippocampal slice preparation. Both extracellular field potentials, the excitatory post-synaptic potential (EPSP) and the population spike, were shown to exhibit a reversible decrease in the presence of 50μM NE. Recurrent inhibition, presumably mediated by basket cell interneurons, was assessed by examining the effect of a preceding conditioning pulse applied to the alvear pathway (antidromic) on stratum radiatum evoked responses. NE perfusion produced a reversible decrease in recurrent inhibitory processes resulting in a disinhibition of pyramidal cell evoked responses. Experiments carried out with intracellular recordings showed closely similar results as the extracellular correlates. The effects of NE on the extracellular field responses recorded in slices obtained from animals in which endogenous NE had been depleted, by intracerebral or intraventricular injections of 6-hydroxydopamine (6-OHDA) were also examined. Perfusion of NE on these slices resulted in a significant decrease in the inhibition of the EPSP response and an enhancement of the population spike as well as multiple spike discharges characteristic of on-going epileptiform activity. It is proposed that NE exerts inhibitory influences directly on both pyramidal and basket cell interneurons, the latter of which would result in disinhibition of pyramidal cell discharge. An imbalance between these two influences, as perhaps occurs following 6-OHDA lesions, may contribute to the generation of epileptiform activity.Medicine, Faculty ofCellular and Physiological Sciences, Department ofGraduat