Abstract
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.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
2-Amino-5-phosphonovalerate / pharmacology
-
Action Potentials / drug effects
-
Action Potentials / physiology*
-
Animals
-
Biophysics
-
Calcium / metabolism
-
Dopamine / metabolism*
-
Dose-Response Relationship, Drug
-
Electric Stimulation / methods
-
Enzyme Inhibitors / pharmacology
-
Excitatory Amino Acid Antagonists / pharmacology
-
Gene Expression Regulation / drug effects
-
Gene Expression Regulation / physiology
-
In Vitro Techniques
-
Inositol 1,4,5-Trisphosphate / analogs & derivatives
-
Inositol 1,4,5-Trisphosphate / pharmacology
-
Intracellular Signaling Peptides and Proteins / pharmacology
-
Long-Term Potentiation / drug effects
-
Long-Term Potentiation / physiology
-
Male
-
Mesencephalon / cytology*
-
Methoxyhydroxyphenylglycol / analogs & derivatives
-
Methoxyhydroxyphenylglycol / pharmacology
-
Neural Pathways / physiology
-
Neuronal Plasticity / drug effects
-
Neuronal Plasticity / physiology*
-
Neurons / drug effects
-
Neurons / physiology*
-
Peptide Fragments / pharmacology
-
Rats
-
Rats, Sprague-Dawley
-
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
-
Receptors, N-Methyl-D-Aspartate / physiology*
-
Time Factors
Substances
-
Enzyme Inhibitors
-
Excitatory Amino Acid Antagonists
-
Intracellular Signaling Peptides and Proteins
-
Peptide Fragments
-
Receptors, N-Methyl-D-Aspartate
-
inositol 1,4,5-trisphosphate 1-(2-nitrophenyl)ethyl ester
-
protein kinase inhibitor peptide (6-24)
-
Methoxyhydroxyphenylglycol
-
2-Amino-5-phosphonovalerate
-
Inositol 1,4,5-Trisphosphate
-
Calcium
-
3,4-dihydroxyphenylglycol
-
Dopamine