protein-kinase-inhibitor-peptide-(6-24) and 3-4-dihydroxyphenylglycol

Bursts of spikes triggered by sensory stimuli in midbrain dopamine neurons evoke phasic release of dopamine in target brain areas, driving reward-based reinforcement learning and goal-directed behavior. NMDA-type glutamate receptors (NMDARs) play a critical role in the generation of these bursts. Here we report LTP of NMDAR-mediated excitatory transmission onto dopamine neurons in the substantia nigra. Induction of LTP requires burst-evoked Ca2+ signals amplified by preceding metabotropic neurotransmitter inputs in addition to the activation of NMDARs themselves. PKA activity gates LTP induction by regulating the magnitude of Ca2+ signal amplification. This form of plasticity is associative, input specific, reversible, and depends on the relative timing of synaptic input and postsynaptic bursting in a manner analogous to the timing rule for cue-reward learning paradigms in behaving animals. NMDAR plasticity might thus represent a potential neural substrate for conditioned dopamine neuron burst responses to environmental stimuli acquired during reward-based learning.

Topics: 2-Amino-5-phosphonovalerate; Action Potentials; Animals; Biophysics; Calcium; Dopamine; Dose-Response Relationship, Drug; Electric Stimulation; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Gene Expression Regulation; In Vitro Techniques; Inositol 1,4,5-Trisphosphate; Intracellular Signaling Peptides and Proteins; Long-Term Potentiation; Male; Mesencephalon; Methoxyhydroxyphenylglycol; Neural Pathways; Neuronal Plasticity; Neurons; Peptide Fragments; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Time Factors