Abstract

The entorhinal cortex connects neocortical areas with the hippocampal formation and other parahippocamal brain areas, and also receives cholinergic projections from the medial septum and dopaminergic projections from the ventral tegmental area. Dopamine and acetylcholine both may contribute to the processing of sensory information in the entorhinal cortex and in other areas of the brain. In Chapter 1, the application of the cholinergic agonist carbachol to entorhinal cortex slices suppressed synaptic transmission in vitro, and experiments determined that the effect was due primarily to activation of M1 muscarinic receptors. Activation of cholinergic receptors also causes a relative facilitation of later responses during theta- and gamma-frequency trains, and because dopamine may modulate gamma and theta oscillations in the entorhinal cortex, Chapter 2 investigated the effect of amphetamine on the amplitudes of synaptic responses during trains of gamma- and theta-frequency stimulation in awake animals. A subset of animals that showed a facilitation of the response to the first pulse of theta-frequency trains due to amphetamine also expressed a synaptic suppression during mobility compared with immobility that was likely due to cholinergic receptor activation. These animals also showed a relative suppression of subsequent responses that was blocked by the D1 receptor antagonist SCH23390 and the D2 receptor antagonist eticlopride. Because previous work in our lab has shown bidirectional effects of differing concentrations of dopamine, Chapter 3 investigated the role of both 10 and 50 μM dopamine in the entorhinal cortex during gamma- and theta-frequency stimulation in vitro. Ten μM dopamine facilitated responses during trains of both frequencies. In contrast, 50 μM dopamine induced a D2 receptor-dependent suppression the first responses and induced a relative facilitation of later responses during the trains, an effect that was only significant for gamma-frequency trains. In general, then, low concentrations of dopamine may enhance repetitive synaptic transmission, while higher concentrations of dopamine may suppress repetitive synaptic transmission within the entorhinal cortex. Because dopamine may modulate learning- related synaptic strengthening, Chapter 4 investigated the effect of 10 μM dopamine on induction of long-term synaptic potentiation (LTP) in entorhinal cortex slices; although dopamine facilitated synaptic responses, it blocked the induction of LTP, suggesting that it may impede learning-related synaptic plasticity. Overall, results indicate that both dopamine and acetylcholine have strong modulatory influences on processes that may affect synaptic integration and plasticity within the entorhinal cortex.