Dopaminergic Modulation of Entorhinal Cortex Function

Dopaminergic Modulation of Entorhinal Cortex Function Douglas A. Caruana, Ph.D. Concordia University, 2008 The neurotransmitter dopamine has been shown to play an important role in the mnemonic functions of the prefrontal cortex, but it is unclear how dopamine may affect sensory and mnemonic processing in the entorhinal cortex. Midbrain dopamine neurons project to the superficial layers of the lateral entorhinal cortex and may modulate olfactory inputs that also terminate in this area. In awake rats, increasing extracellular dopamine levels in the entorhinal cortex with a selective dopamine reuptake inhibitor facilitated basal synaptic transmission in piriform cortex inputs to layer II. Experiments in slices of the entorhinal cortex maintained in vitro demonstrated concentration-dependent, bidirectional effects of dopamine on synaptic responses; a low 10 uM concentration of dopamine enhanced synaptic responses and higher concentrations of 50 and 100 uM dopamine suppressed responses. The facilitation of responses was dependent on activation of D-i receptors and the suppression was dependent on D2 receptors. Intracellular recordings of mixed and isolated synaptic responses demonstrated that the dopaminergic suppression is mediated by a D2 receptor-dependent reduction in glutamate release and a D^dependent drop in cellular input resistance. The drop in input resistance was mediated by a D1 receptordependent K conductance. In additional experiments, patterned stimulation of the piriform cortex that induces persistent changes in synaptic strength in the