Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-1-28
pubmed:abstractText
Substance P (SP) is co-localized and co-released with gamma-amino butyric acid (GABA) from approximately 50% of GABAergic medium spiny neurons (MSNs) in the striatum. MSNs innervate several cellular targets including neighboring MSNs and cholinergic interneurons via collaterals. However, the functional role of SP release onto striatal interneurons is unknown. Here we examined SP-mediated actions on inhibitory synaptic transmission in cholinergic interneurons using whole-cell recordings in mouse corticostriatal slices. We found that SP selectively suppressed GABA(A) receptor-mediated inhibitory post-synaptic currents (IPSCs), but not excitatory post-synaptic currents (EPSCs) in cholinergic interneurons. In contrast, SP did not alter IPSCs in fast-spiking interneurons and MSNs. SP suppressed IPSC amplitude in a concentration-dependent and reversible manner, and the NK1 receptor antagonist RP67580 attenuated the SP-mediated suppression. In addition, RP67580 alone enhanced the evoked IPSC amplitude in cholinergic interneurons, suggesting an endogenous action of SP on regulation of inhibitory synaptic transmission. SP did not alter the paired-pulse ratio, but reduced the amplitudes of GABA(A) agonist muscimol-induced outward currents and miniature IPSCs in cholinergic interneurons, suggesting SP exerts its effects primarily at the post-synaptic site. Our results indicate that the physiological effects of SP are to enhance the activity of striatal cholinergic interneurons and provide a rationale for designing potential new antiparkinsonian agents.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1873-7064
pubmed:author
pubmed:copyrightInfo
Published by Elsevier Ltd.
pubmed:issnType
Electronic
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
413-22
pubmed:dateRevised
2011-6-10
pubmed:meshHeading
pubmed-meshheading:19786036-Action Potentials, pubmed-meshheading:19786036-Animals, pubmed-meshheading:19786036-Cerebral Cortex, pubmed-meshheading:19786036-Corpus Striatum, pubmed-meshheading:19786036-Excitatory Postsynaptic Potentials, pubmed-meshheading:19786036-GABA-A Receptor Agonists, pubmed-meshheading:19786036-Inhibitory Postsynaptic Potentials, pubmed-meshheading:19786036-Interneurons, pubmed-meshheading:19786036-Mice, pubmed-meshheading:19786036-Mice, Inbred C57BL, pubmed-meshheading:19786036-Neural Inhibition, pubmed-meshheading:19786036-Neurons, pubmed-meshheading:19786036-Patch-Clamp Techniques, pubmed-meshheading:19786036-Receptors, GABA-A, pubmed-meshheading:19786036-Receptors, Neurokinin-1, pubmed-meshheading:19786036-Substance P, pubmed-meshheading:19786036-Synapses, pubmed-meshheading:19786036-Synaptic Transmission
pubmed:year
2010
pubmed:articleTitle
Substance P selectively modulates GABA(A) receptor-mediated synaptic transmission in striatal cholinergic interneurons.
pubmed:affiliation
Department of Molecular & Integrative Physiology, University of Illinois, Urbana, IL 61801, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural