Trifling matters: differential regulation of feedforward and feedback interneurons of the dentate gyrus by release of endogenous norepinephrine

Abstract

Norepinephrine is known to play an important role in hippocampal function. Norepinephrine is required for long-term potentiation in dentate gyrus, and norepinephrine blockade or depletion can interfere with acquisition and retrieval in hippocampal dependent tasks. While gross measures of hippocampal function such as evoked potentials demonstrate plastic changes under the influence of norepinephrine, single unit studies to date report suppression of principle cell firing and increased firing rates for inhibitory interneurons. Such changes should reflect an increase in inhibition and would predict a decrease in plasticity. -- In this thesis I examine the effect of "natural" synaptic release of norepinephrine on spontaneous firing rates of cells in dentate gyrus, with concomitant electroencephalographic recording. Physiologically identified interneurons are classified as either feedforward or feedback depending on whether they were activated prior to, or after, the perforant path evoked population spike. Principle cells are identified by their characteristic firing properties and a firing latency within the window of the performant path evoked population spike. -- In this study feedforward interneurons virtually cease firing in response to synaptic release of norepinephrine, producing a period of disinhibition which lasts several minutes. Simultaneously, cells identified as principle cells increase their firing rates. Feedback interneurons demonstrated a mixed profile with some cells increasing their firing rates and others decreasing their firing rates. -- Fast Fourier analysis of the electroencephalographic recordings revealed a increase in relative power in the theta band as reported previously, together with a decrease in overall power and a decrease in relative power of the gamma band. These data are compared to previous studies of noradrenergic effects on single unit, evoked potential, and electroencephalography measures in the literature. The results are also compared to existing models of plasticity such as long-term potentiation and gamma power regulated acquisition and recall of hippocampal representations. Finally a new framework is proposed as to how norepinephrine may play a role in plasticity by allowing new information to be bound to mature hippocampal representations.