Understanding the mechanisms of drug addiction is a major goal of modern neurobiology. At the heart of the problem lies an alteration in the dopaminergic neuromodulatory system. The hippocampus is a region of the brain that has been implicated in drug reward circuitry, and is heavily innervated by ventral tegmental dopaminergic terminals. Recently, much attention has been devoted to voltage-gated ion channels in the dendrites of CA1 pyramidal neurons of the hippocampus, yet little of this attention has focused on its possible importance. In drug addiction. My preliminary evidence suggests that voltage-gated ion channels in CA1 neurons can undergo plastic changes following synaptic conditioning., which is a particularly interested phenomenon considering that alterations in intrinsic excitability of neurons have been reported in nucleus accumbal neurons following psychostimulant sensitization. In this proposal the goal is to understand how plasticity of dendritic intrinsic conductances could contribute to the neuroadaptation seen during drug addiction. Specifically, I plan to explore acute and chronic dopaminergic modulation of CA1 pyramidal dendritic function using both in vitro and in vitro pharmacological manipulations.
| Cooper, Donald C; Moore, Shannon J; Staff, Nathan P et al. (2003) Psychostimulant-induced plasticity of intrinsic neuronal excitability in ventral subiculum. J Neurosci 23:9937-46 |
| Staff, Nathan P; Spruston, Nelson (2003) Intracellular correlate of EPSP-spike potentiation in CA1 pyramidal neurons is controlled by GABAergic modulation. Hippocampus 13:801-5 |
