JN AJP: Advances in Physiology Education
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

J Neurophysiol (January 2, 2003). doi:10.1152/jn.00780.2002
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
89/4/1929    most recent
00780.2002v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hsu, F.-C.
Right arrow Articles by Smith, S. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hsu, F.-C.
Right arrow Articles by Smith, S. S.
Submitted on September 9, 2002
Accepted on December 18, 2002

Neurosteroid effects on GABAergic synaptic plasticity in hippocampus

Fu-Chun Hsu1, Robert Waldeck2, Donald S. Faber3, and Sheryl S. Smith4*

1 Pediatrics/Neurology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Neurobiology and Anatomy, MCP-Hahnemann University, Philadelphia, PA, USA
2 Biology, University of Scranton, Scranton, PA, USA; Neurobiology and Anatomy, MCP-Hahnemann University, Philadelphia, PA, USA
3 Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA; Neurobiology and Anatomy, MCP-Hahnemann University, Philadelphia, PA, USA
4 Physiology and Pharmacology, SUNY Downstate Medical Center, Brooklyn, NY, USA; Neurobiology and Anatomy, MCP-Hahnemann University, Philadelphia, PA, USA

* To whom correspondence should be addressed. E-mail: sheryl.smith{at}downstate.edu.

We have previously reported that short-term (48-72 hr.) exposure to the GABA-modulatory steroid 3{alpha}-OH-5{alpha}-pregnan-20-one (3{alpha},5{alpha}-THP) increases expression of the {alpha}4 subunit of the GABAA receptor (GABAR) in the hippocampus of adult rats. This change in subunit composition was accompanied by altered pharmacology and an acceleration of the decay time constant ({tau}) for GABA-gated current of pyramidal cells acutely isolated from CA1 hippocampus similar to what we have reported following withdrawal from the steroid after chronic long-term administration. Because GABAR can be localized to either synaptic or extrasynaptic sites, here we test the hypothesis that this change is mediated by synaptic {alpha}4-containing GABAR. To this end, we evaluated the decay kinetics of TTX-resistant miniature inhibitory post-synaptic currents (mIPSCs) recorded from CA1 pyramidal cells in hippocampal slices following 48 hr. treatment with 3{alpha},5{alpha}/{beta}-THP (10 mg/kg, intraperitoneal injection). Hormone treatment produced a marked acceleration in the fast decay time constant ({tau}fast) of GABAergic mIPSCs. This effect was prevented by suppression of {alpha}4-subunit expression with antisense (AS) oligonucleotide, suggesting that hormone treatment increases expression of {alpha}4-containing GABAR subsynaptically. This conclusion was further supported by pharmacological data from 3{alpha},5{beta}-THP-treated animals demonstrating a bimodal distribution of {tau}s for individual mIPSCs following bath application of the {alpha}4-selective benzodiazepine RO15-4513 with a shift to slower values. Because 40-50% of the individual {tau}s were also shifted to slower values following bath application of the non-{alpha}4-selective benzodiazepine agonist lorazepam (LZM), we suggest that the number of GABAR synapses containing {alpha}4 subunits is equivalent to those which do not following 48 hr. administration of 3{alpha},5{beta}-THP. The decrease in GABAR-mediated charge transfer resulting from accelerated current decay may then result in increased excitability of the hippocampal circuitry, an effect consistent with the increased behavioral excitability we have previously demonstrated.




This article has been cited by other articles:


Home page
 J. Physiol.Home page
E. A. Mitchell, L. J. Gentet, J. Dempster, and D. Belelli
GABAA and glycine receptor-mediated transmission in rat lamina II neurones: relevance to the analgesic actions of neuroactive steroids
J. Physiol., September 15, 2007; 583(3): 1021 - 1040.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
A. H. Lagrange, E. J. Botzolakis, and R. L. Macdonald
Enhanced macroscopic desensitization shapes the response of {alpha}4 subtype-containing GABAA receptors to synaptic and extrasynaptic GABA
J. Physiol., February 1, 2007; 578(3): 655 - 676.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
H. P. Goodkin, J.-L. Yeh, and J. Kapur
Status Epilepticus Increases the Intracellular Accumulation of GABAA Receptors
J. Neurosci., June 8, 2005; 25(23): 5511 - 5520.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
S. S Smith and Q. H. Gong
Neurosteroid administration and withdrawal alter GABAA receptor kinetics in CA1 hippocampus of female rats
J. Physiol., April 15, 2005; 564(2): 421 - 436.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
J. L Fisher
The {alpha}1 and {alpha}6 subunit subtypes of the mammalian GABAA receptor confer distinct channel gating kinetics
J. Physiol., December 1, 2004; 561(2): 433 - 448.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 2003 by the The American Physiological Society.