Noradrenergic function in the dentate gyrus: an electrophysiological investigation in vitro

Lacaille, Jean-Claude (1984) Noradrenergic function in the dentate gyrus: an electrophysiological investigation in vitro. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

Although the hippocampal formation is known to receive an extensive noradrenergic input, there is some controversy about the effects of norepinephrine (NE) on hippocampal neurons and it is not known whether the effects of NE are identical in all the major subdivisions of the hippocampal formation. The objectives of the present study were to evaluate in detail the physiological effects of NE in the rat dentate gyrus in vitro and to compare these effects with those previously reported for hippocampal pyramidal cells and for dentate gyrus granule cells. -- Granule cell responses were measured electrophysiologically by recording perforant path evoked field potentials. Responses were digitized and analyzed by a microprocessor based system for EPSP slope or amplitude, population spike onset latency and population spike amplitude. -- NE produced dose-dependent changes in evoked responses which were maximal after superfusion of 10 uM NE for 10 minutes. Typical effects of 10 uM NE were to increase population spike amplitude and decrease population spike onset latency. Effects of NE on extracellular EPSP parameters were less consistent: EPSP slope was generally increased and EPSP amplitude was most often unchanged although sometimes increased. The effects of NE on population spike amplitude were of the greatest magnitude and duration. Long-lasting increases in population spike amplitude were observed in 24% of the cases. -- The effects of NE were mediated by beta-adrenergic receptors. Timolol but not phentolamine blocked them and isoproterenol but not phenylephrine mimicked them. The population spike-EPSP relationship suggested that 50% of the increase in population spike amplitude was due to synaptic effects and 50% to extrasynaptic effects of NE. NE did not increase the antidromic population spike, thus the enhanced responsiveness was not due to granule cell soma membrane excitability changes. NE superfusion without concurrent perforant path stimulation produced enhancement of subsequently evoked responses. Hence, these effects of NE were activity-independent. In contrast to NE, 5-HT produced decreases in perforant path evoked responses. -- These results suggest that the noradrenergic input to the dentate gyrus facilitates the granule cell responses to afferent inputs. These results are discussed in terms of noradrenergic function in the dentate gyrus, are related to hippocampal function in physiological and behavioral perspectives, and are compared to the effects of NE in other central nervous system (CNS) regions. -- Keywords: norepinephrine; dentate gyrus; hippocampal slice; EPSP; population spike; long-lasting potentiation; beta receptors.

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