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Effects of a naturally occurring neurosteroid on GABA A IPSCs during development in rat hippocampal or cerebellar slices
Author(s) -
Cooper Elizabeth J.,
Johnston Graham A. R.,
Edwards Frances A.
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.00437.x
Subject(s) - neuroactive steroid , hippocampal formation , gabaa receptor , endocrinology , cerebellum , medicine , gabaergic , patch clamp , allopregnanolone , granule cell , chemistry , biology , electrophysiology , neuroscience , receptor , inhibitory postsynaptic potential , dentate gyrus
1 The effects of the naturally occurring neurosteroid tetrahydrodeoxycorticosterone (THDOC) on GABA A receptor‐mediated miniature, spontaneous and evoked IPSCs was tested using patch‐clamp techniques in slices of hippocampus and cerebellum from rats at two developmental stages (≈10 and ≈20 days postnatal). The cells studied were hippocampal granule cells and cerebellar Purkinje and granule cells. 2 Most miniature GABAergic currents (mIPSCs) decayed with two exponentials and neurosteroids caused a ≈4‐fold increase in the decay time constant of the second exponential at the highest concentration used (2 μ m ). Similar effects were seen at high concentrations of THDOC (1‐2 μ m ) in all cell groups tested. No effects were seen on amplitude or rise time of mIPSCs. 3 The effects of THDOC (1 μ m ) were shown to be stereoselective and rapidly reversible, indicating that the neurosteroid binds to the GABA A receptor, rather than acting genomically. 4 At concentrations of THDOC likely to occur physiologically (50‐100 n m ), the decay time of IPSCs was also enhanced (25‐50 %) in all cerebellar cell groups tested. In contrast, at 100 n m THDOC, seven of 11 hippocampal granule cells were sensitive from the 10 day group but the 20 day hippocampal granule cells showed no significant enhancement in the presence of these lower concentrations of THDOC. 5 The differences in sensitivity of hippocampal and cerebellar cells to THDOC are compared to data reported in the literature on regional development of expression of different receptor subunits in the brain and it is suggested that the progressive relative insensitivity of the 20 day hippocampal cells may depend on increasing expression of the δ subunit of the GABA A receptor and possibly an increase in the α4 subunit.