Linked Life Data

12904482

Source:http://linkedlifedata.com/resource/pubmed/id/12904482

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2003-8-7
pubmed:abstractText
The globus pallidus (GP) is a key GABAergic nucleus in the basal ganglia (BG). The predominant input to the GP is an inhibitory striatal projection that forms the first synapse in the indirect pathway. The GP GABAergic neurons project to the subthalamic nucleus, providing an inhibitory control of these glutamatergic cells. Given its place within the BG circuit, it is not surprising that alterations in GP firing pattern are postulated to play a role in both normal and pathological motor behavior. Because the inhibitory striatal input to the GP may play an important role in shaping these firing patterns, we set out to determine the role that the group III metabotropic glutamate receptors (GluRs) play in modulating transmission at the striatopallidal synapse. In rat midbrain slices, electrical stimulation of the striatum evoked GABA(A)-mediated IPSCs recorded in all three types of GP neurons. The group III mGluR-selective agonist L-(+)-2-amino-4-phosphonobutyric acid (L-AP4) inhibited these IPSCs through a presynaptic mechanism of action. L-AP4 exhibited high potency and a pharmacological profile consistent with mediation by mGluR4. Furthermore, the effect of L-AP4 on striatopallidal transmission was absent in mGluR4 knock-out mice, providing convincing evidence that mGluR4 mediates this effect. The finding that mGluR4 may selectively modulate striatopallidal transmission raises the interesting possibility that activation of mGluR4 could decrease the excessive inhibition of the GP that has been postulated to occur in Parkinson's disease. Consistent with this, we find that intracerebroventricular injections of L-AP4 produce therapeutic benefit in both acute and chronic rodent models of Parkinson's disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
6
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7218-26
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12904482-Adrenergic Uptake Inhibitors, pubmed-meshheading:12904482-Aminobutyric Acids, pubmed-meshheading:12904482-Animals, pubmed-meshheading:12904482-Corpus Striatum, pubmed-meshheading:12904482-Disease Models, Animal, pubmed-meshheading:12904482-Electric Stimulation, pubmed-meshheading:12904482-Excitatory Amino Acid Agonists, pubmed-meshheading:12904482-Globus Pallidus, pubmed-meshheading:12904482-Male, pubmed-meshheading:12904482-Mice, pubmed-meshheading:12904482-Mice, Knockout, pubmed-meshheading:12904482-Motor Activity, pubmed-meshheading:12904482-Neural Inhibition, pubmed-meshheading:12904482-Parkinson Disease, pubmed-meshheading:12904482-Rats, pubmed-meshheading:12904482-Rats, Sprague-Dawley, pubmed-meshheading:12904482-Receptors, Metabotropic Glutamate, pubmed-meshheading:12904482-Reserpine, pubmed-meshheading:12904482-Synapses, pubmed-meshheading:12904482-Synaptic Transmission, pubmed-meshheading:12904482-gamma-Aminobutyric Acid
pubmed:year
2003
pubmed:articleTitle
Group III metabotropic glutamate receptor-mediated modulation of the striatopallidal synapse.
pubmed:affiliation
Department of Neuroscience, Merck Research Laboratories, West Point, Pennsylvania 19486-0004, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't