Glutamate-mediated plasticity in corticostriatal networks: role in adaptive motor learning.
Little is known about how memories of new voluntary motor actions, also known as procedural memory, are formed at the molecular level. Our work examining acquisition of lever-pressing for food in rats has shown that activation of glutamate NMDA receptors, within broadly distributed but interconnected regions (e.g., nucleus accumbens core, prefrontal cortex, basolateral amygdala), is critical for such learning to occur. This receptor stimulation triggers intracellular cascades that involve protein phosphorylation and new protein synthesis. In support of this idea, we have found that posttrial inhibition of protein synthesis in the ventral striatum impairs learning, whereas posttrial NMDA receptor blockade does not. More recent data show extension of this network to the central amygdala, where infusions of NMDA antagonists also impair learning. We hypothesize that activity in this distributed network (including dopaminergic activity and perhaps muscarinic cholinergic activity) computes coincident events and thus enhances the probability that temporally related actions and events (e.g., lever pressing and delivery of reward) become associated. Such basic mechanisms of plasticity within this reinforcement learning network also appear to be profoundly affected in addiction.
Kelley
Ann E
AE
Department of Psychiatry and Neuroscience Training Program, University of Wisconsin-Madison Medical School, 6001 Research Park Boulevard, Madison, Wisconsin 53719, USA.
Andrzejewski
Matthew E
ME
Baldwin
Anne E
AE
Hernandez
Pepe J
PJ
Pratt
Wayne E
WE
D000223:Adaptation, Psychological / Q000502:physiology; D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D004298:Dopamine / Q000502:physiology; D005971:Glutamates / Q000502:physiology*; D006801:Humans; D007858:Learning / Q000502:physiology*; D008032:Limbic System / Q000502:physiology; D017072:Neostriatum / Q000502:physiology*; D009415:Nerve Net / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009473:Neuronal Plasticity / Q000502:physiology*; D009714:Nucleus Accumbens / Q000502:physiology; D017397:Prefrontal Cortex / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D005971:Glutamates; D009419:Nerve Tissue Proteins; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D004298:Dopamine