Dopaminergic modulation of striatal plateau depolarizations in corticostriatal organotypic cocultures.
BACKGROUND
It has been proposed that dopamine (DA) sustains up states in striatal medium spiny neurons (MSN). Testing this hypothesis requires an in vitro preparation, but up states are typically only observed in vivo.


OBJECTIVE
In this study, we used corticostriatal organotypic cocultures, a preparation in which up states have been previously observed, to test the DA control of cortically-driven plateau depolarizations.


RESULTS
After 7-21 days in vitro in serum-free conditions, plateau depolarizations resembling up states were only observed in cultures with a critical extent of striatal DA innervation. These plateaus were completely blocked by the non-NMDA antagonist CNQX and significantly shortened by the NMDA antagonist APV or the D(1) antagonist SCH23390. Intracellular interruption of Ca(++) or protein-kinase A (PKA) signaling also eliminated the plateaus. The D(2) antagonist eticlopride failed to disrupt the plateaus, but significantly increased MSN excitability.


CONCLUSIONS
These results suggest that coincident activation of corticostriatal glutamatergic and mesostriatal DA transmission may set ensembles of MSN into prolonged depolarizations through a D(1) enhancement of striatal NMDA function in a Ca(++) and PKA-dependent manner.
Tseng
Kuei Y
KY
Center for Neuropharmacology and Neuroscience, Albany Medical College, 47 New Scotland Ave (MC-136), Albany, NY 12208, USA.
Snyder-Keller
Abigail
A
O'Donnell
Patricio
P
D000200:Action Potentials; D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D018920:Coculture Techniques; D003342:Corpus Striatum / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D009431:Neural Conduction; D009474:Neurons / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D016548:Prosencephalon / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism; D009435:Synaptic Transmission; D013997:Time Factors; D046509:Tissue Culture Techniques; D017557:Ventral Tegmental Area / Q000378:metabolism
D018377:Neurotransmitter Agents; D018091:Receptors, AMPA; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D005973:Glutamine; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium; D004298:Dopamine