Linked Life Data

15548642

Source:http://linkedlifedata.com/resource/pubmed/id/15548642

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
46
pubmed:dateCreated
2004-11-19
pubmed:abstractText
Striatal cholinergic interneurons are critical elements of the striatal circuitry controlling motor planning, movement, and associative learning. Intrastriatal release of dopamine and inhibition of interneuron activity is thought to be a critical link between behaviorally relevant events, such as reward, and alterations in striatal function. However, the mechanisms mediating this modulation are unclear. Using a combination of electrophysiological, molecular, and computational approaches, the studies reported here show that D2 dopamine receptor modulation of Na+ currents underlying autonomous spiking contributes to a slowing of discharge rate, such as that seen in vivo. Four lines of evidence support this conclusion. First, D2 receptor stimulation in tissue slices reduced the autonomous spiking in the presence of synaptic blockers. Second, in acutely isolated neurons, D2 receptor activation led to a reduction in Na+ currents underlying pacemaking. The modulation was mediated by a protein kinase C-dependent enhancement of channel entry into a slow-inactivated state at depolarized potentials. Third, the sodium channel blocker TTX mimicked the effects of D2 receptor agonists on pacemaking. Fourth, simulation of cholinergic interneuron pacemaking revealed that a modest increase in the entry of Na+ channels into the slow-inactivated state was sufficient to account for the slowing of pacemaker discharge. These studies establish a cellular mechanism linking dopamine and the reduction in striatal cholinergic interneuron activity seen in the initial stages of associative learning.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10289-301
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
D2 dopamine receptor-mediated modulation of voltage-dependent Na+ channels reduces autonomous activity in striatal cholinergic interneurons.
pubmed:affiliation
Department of Physiology and Institute for Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural