Neuromodulation of neocortical long-term potentiation in the adult, freely moving rat

Abstract

<p>Correlated firing between adjacent neurons results in increased synaptic efficacy between synapses. This effect is called long-term potentiation (LTP) and is widely regarded as the mechanism underlying learning and memory because it is long-lasting and has been demonstrated in areas of the brain involved in information encoding and storage. Although definitive proof that LTP underlies learning and memory remains elusive, mounting evidence suggests that LTP, learning and memory are related and that LTP is a viable candidate for information storage. Understanding the nature of the relationship between LTP, learning and memory requires further investigation into the characteristics of LTP in the neocortex of the behaving rat. Neuromodulators have proven integral for successful learning. For this reason, their effect on LTP is of high interest. While neuromodulation of neocortical LTP has been studied in vitro , it has never before been investigated in the whole organism. This thesis explored the effects of cholinergic, noradrenergic and dopaminergic modulation on neocortical LTP induction in the behaving rat. In the cholinergic and noradrenergic experiments, significant group-by-session interactions were obtained in the early-component (monosynaptic) measures of LTP induction: Scopolamine, the cholinergic antagonist, blocked LTP while elenbuterol, a beta-noradrenergic agonist, enhanced LTP. The measure of LTP taken from the polysynaptic component resulted in significant group-by-session interactions for three modulatory manipulations. Pilocarpine, the cholinergic agonist, and apomorphine, the dopamine agonist, facilitated LTP. Clenbuterol and the beta-noradrenergic antagonist propranolol attenuated and tended toward attenuating LTP, respectively. Additionally, the neuroleptic haloperidol induced LTD. Taken together, these results provide more evidence for a relationship between UP and information processing. However, these results also highlight the complexity of neuromodulatory actions. Further research will aim to determine a more direct link between learning and memory by ascertaining dose-responses curves and applying them to behavioral tasks.</p>