The neuromodulator dopamine is implicated in mechanisms of attention and reinforcement of learning. Many brain disorders (schizophrenia, attention deficit, Parkinson disease, alcohol and drug addition) involve the disruption of dopaninergic function, and cause different forms of memory impairment. Long-term potentiation (LTP) in the CA1 region of the hippocampus is a convenient model for studies of cellular mechanisms of memory. Our data with field potential recordings indicate that D1 dopamine modulations enhances early LTP by a cAMP- dependent mechanism. This proposal deals with the intracellular targets of dopamine and cAMP action. Two fundamental possibilities for the enhancement of LTP by dopamine will be addressed: D1 activation could increase depolarization during the tetanus or it could affect the enzymatic mechanisms of plasticity. The first possibility, D1 action on electrical properties of pyramidal cells, will be accessed by whole-cell recording methods (Aim 1). The second possibility, that D1 and cAMP affects the enzymatic machinery of LPT, will be analyzed by voltage clamp with intracellular perfusion of substances in interest (Aim 2).
| Otmakhova, N A; Otmakhov, N; Mortenson, L H et al. (2000) Inhibition of the cAMP pathway decreases early long-term potentiation at CA1 hippocampal synapses. J Neurosci 20:4446-51 |
| Otmakhova, N A; Lisman, J E (2000) Dopamine, serotonin, and noradrenaline strongly inhibit the direct perforant path-CA1 synaptic input, but have little effect on the Schaffer collateral input. Ann N Y Acad Sci 911:462-4 |
