Document Detail


Distinct cellular properties of identified dopaminergic and GABAergic neurons in the mouse ventral tegmental area.
MedLine Citation:
PMID:  21646409     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The midbrain ventral tegmental area (VTA) contains neurons largely with either a dopaminergic (DAergic) or GABAergic phenotype. Physiological and pharmacological properties of DAergic neurons have been determined using tyrosine hydroxylase (TH) immunohistochemistry but many properties overlap with non-DAergic neurons presumed to be GABAergic. This study examined properties of GABAergic neurons, non-GABAergic neurons and TH-immunopositive neurons in VTA of GAD67-GFP knock-in mice. Ninety-eight per cent of VTA neurons were either GAD-GFP or TH positive,with the latter being five times more abundant. During cell-attached patch-clamp recordings, GAD-GFP neurons fired brief action potentials that could be completely distinguished from those of non-GFP neurons. Pharmacologically, the μ-opioid agonist DAMGO inhibited firing of action potentials in 92% of GAD-GFP neurons but had no effect in non-GFP neurons. By contrast, dopamine invariably inhibited action potentials in non-GFP neurons but only did so in 8% of GAD-GFP neurons. During whole-cell recordings, the narrower width of action potential in GAD-GFP neurons was also evident but there was considerable overlap with non-GFP neurons. GAD-GFP neurons invariably failed to exhibit the potassium-mediated slow depolarizing potential during injection of positive current that was present in all non-GFP neurons. Under voltage-clamp the cationic current, I(h), was found in both types of neurons with considerable overlap in both amplitude and kinetics. These distinct cellular properties may thus be used to confidently discriminate GABAergic and DAergic neurons in VTA during in vitro electrophysiological recordings.
Authors:
Billy Chieng; Yael Azriel; Sarasa Mohammadi; MacDonald J Christie
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-06-06
Journal Detail:
Title:  The Journal of physiology     Volume:  589     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-02     Completed Date:  2012-04-17     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  3775-87     Citation Subset:  IM    
Affiliation:
Brain and Mind Research Institute, University of Sydney, Level 6, Building F, 94 Mallett Street, M02F, Camperdown, NSW 2050, Australia. chin.chieng@sydney.edu.au
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MeSH Terms
Descriptor/Qualifier:
Action Potentials / drug effects
Animals
Dopamine / metabolism
Dopaminergic Neurons / cytology*,  metabolism
Electrophysiology / methods
Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
GABAergic Neurons / cytology*,  metabolism
Gene Knock-In Techniques / methods
Glutamate Decarboxylase / metabolism
Green Fluorescent Proteins / metabolism
Immunohistochemistry / methods
Lysine / analogs & derivatives,  metabolism
Male
Mice
Patch-Clamp Techniques / methods
Potassium / metabolism
Tyrosine 3-Monooxygenase / metabolism
Ventral Tegmental Area / cytology*,  drug effects,  metabolism
Chemical
Reg. No./Substance:
100929-53-1/Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; 147336-22-9/Green Fluorescent Proteins; 56-87-1/Lysine; 7440-09-7/Potassium; EC 1.14.16.2/Tyrosine 3-Monooxygenase; EC 4.1.1.15/Glutamate Decarboxylase; G6D6147J22/biocytin
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