Abstract
Dopamine input to the striatum is required for voluntary motor movement, behavioral reinforcement, and responses to drugs of abuse. It is speculated that these functions are dependent on either excitatory or inhibitory modulation of corticostriatal synapses onto medium spiny neurons (MSNs). While dopamine modulates MSN excitability, a direct presynaptic effect on the corticostriatal input has not been clearly demonstrated. We combined optical monitoring of synaptic vesicle exocytosis from motor area corticostriatal afferents and electrochemical recordings of striatal dopamine release to directly measure effects of dopamine at the level of individual presynaptic terminals. Dopamine released by either electrical stimulation or amphetamine acted via D2 receptors to inhibit the activity of subsets of corticostriatal terminals. Optical and electrophysiological data suggest that heterosynaptic inhibition was enhanced by higher frequency stimulation and was selective for the least active terminals. Thus, dopamine, by filtering less active inputs, appears to reinforce specific sets of corticostriatal synaptic connections.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Afferent Pathways / drug effects
-
Afferent Pathways / metabolism*
-
Afferent Pathways / ultrastructure
-
Amphetamine / pharmacology
-
Animals
-
Calcium Signaling / drug effects
-
Calcium Signaling / physiology
-
Cerebral Cortex / drug effects
-
Cerebral Cortex / metabolism*
-
Cerebral Cortex / ultrastructure
-
Dopamine / metabolism*
-
Electric Stimulation
-
Excitatory Postsynaptic Potentials / drug effects
-
Excitatory Postsynaptic Potentials / physiology
-
Exocytosis / drug effects
-
Exocytosis / physiology
-
Feedback / drug effects
-
Feedback / physiology
-
Glutamic Acid / metabolism*
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Neostriatum / drug effects
-
Neostriatum / metabolism*
-
Neostriatum / ultrastructure
-
Neural Inhibition / drug effects
-
Neural Inhibition / physiology
-
Presynaptic Terminals / drug effects
-
Presynaptic Terminals / metabolism*
-
Presynaptic Terminals / ultrastructure
-
Pyridinium Compounds
-
Quaternary Ammonium Compounds
-
Receptors, Dopamine D2 / agonists
-
Receptors, Dopamine D2 / metabolism
-
Substantia Nigra / drug effects
-
Substantia Nigra / metabolism
-
Substantia Nigra / ultrastructure
-
Synaptic Transmission / drug effects
-
Synaptic Transmission / physiology*
-
Synaptic Vesicles / drug effects
-
Synaptic Vesicles / metabolism
-
Synaptic Vesicles / ultrastructure
Substances
-
FM1 43
-
Pyridinium Compounds
-
Quaternary Ammonium Compounds
-
Receptors, Dopamine D2
-
Glutamic Acid
-
Amphetamine
-
Dopamine