Document Detail


Differential modulation of nucleus accumbens synapses.
MedLine Citation:
PMID:  12091540     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The nucleus accumbens (NAcc) is a brain region involved in functions ranging from motivation and reward to feeding and drug addiction. The NAcc is typically divided into two major subdivisions, the shell and the core. The primary output neurons of both of these areas are medium spiny neurons (MSNs), which are quiescent at rest and depend on the relative input of excitatory and inhibitory synapses to determine when they fire action potentials. These synaptic inputs are, in turn, regulated by a number of neurochemical signaling agents that can ultimately influence information processing in the NAcc. The present study characterized the ability of three major signaling pathways to modulate synaptic transmission in NAcc MSNs and compared this modulation across different synapses within the NAcc. The opioid [Met](5)enkephalin (ME) inhibited excitatory postsynaptic currents (EPSCs) in shell MSNs, an effect mediated primarily by micro-opioid receptors. Forskolin, an activator of adenylyl cyclase, potentiated shell EPSCs. An analysis of miniature EPSCs indicated a primarily presynaptic site of action, although a smaller postsynaptic effect may have also contributed to the potentiation. Adenosine and an adenosine A(1)-receptor agonist inhibited shell EPSCs, although no significant tonic inhibition by endogenous adenosine was detected. The effects of these signaling agents were then compared across four different synapses in the NAcc: glutamatergic EPSCs and GABAergic inhibitory postsynaptic currents (IPSCs) in both the core and shell subregions. ME inhibited all four of these synapses but produced a significantly greater inhibition of shell IPSCs than the other synapses. Forskolin produced an increase in transmission at each of the synapses tested. However, analysis of miniature IPSCs in the shell showed no sign of a postsynaptic contribution to this potentiation, in contrast to the shell miniature EPSCs. Tonic inhibition of synaptic currents by endogenous adenosine, which was not observed in shell EPSCs, was clearly present at the other three synapses tested. These results indicate that neuromodulation can vary between the different subregions of the NAcc and between the different synapses within each subregion. This may reflect differences in neuronal interconnections and functional roles between subregions and may contribute to the effects of drugs acting on these systems.
Authors:
James M Brundege; John T Williams
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neurophysiology     Volume:  88     ISSN:  0022-3077     ISO Abbreviation:  J. Neurophysiol.     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-07-01     Completed Date:  2002-09-06     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0375404     Medline TA:  J Neurophysiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  142-51     Citation Subset:  IM    
Affiliation:
The Vollum Institute, Oregon Health and Science University, Portland, Oregon 97201, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine / metabolism,  pharmacology
Animals
Electric Conductivity
Excitatory Postsynaptic Potentials / drug effects
Forskolin / pharmacology
Male
Narcotics / pharmacology
Neurons / physiology
Nucleus Accumbens / physiology*
Rats
Rats, Wistar
Synapses / drug effects,  physiology*
Grant Support
ID/Acronym/Agency:
DA-05861/DA/NIDA NIH HHS; DA-08163/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Narcotics; 58-61-7/Adenosine; 66428-89-5/Forskolin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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