Journal
BRAIN RESEARCH REVIEWS
Volume 57, Issue 2, Pages 506-519Publisher
ELSEVIER
DOI: 10.1016/j.brainresrev.2007.04.009
Keywords
steroid; neurotransmitter; release; channel; presynaptic; plasticity
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Funding
- NIAAA NIH HHS [R01 AA015614-04, R01 AA015614] Funding Source: Medline
- NIMH NIH HHS [R01 MH070386-03, R01 MH070386-04] Funding Source: Medline
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH070386] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [R01AA015614] Funding Source: NIH RePORTER
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It is well established that sulfated steroids regulate synaptic transmission by altering the function of postsynaptic neurotransmitter receptors. In recent years, evidence from several laboratories indicates that these agents also regulate glutamatergic synaptic transmission at the presynaptic level in an age-dependent manner. In developing neurons, pregnenolone sulfate (PREGS) increases the probability of glutamate release, as evidenced by an increase in the frequency of AMPA receptor-mediated miniature excitatory postsynaptic currents and a decrease in paired-pulse facilitation. In hippocampal slices from postnatal day 3-5 rats, this effect is mediated by an increase in Ca2+ levels in the axonal terminal that depends on presynaptic NMDA receptors. This is followed by delayed potentiation of postsynaptic AMPA receptor currents. Importantly, depolarization of postsynaptic neurons, inhibition of hydroxysteroid sulfatase activity and acute exposure to ethanol mimics the effect of exogenous PREGS application. This developmental form of synaptic plasticity cannot be observed in slices from rats older than postnatal day 6, when presynaptic NMDA receptors are no longer expressed in CA1 hippocampal region. Both in the CA1 hippocampal region and the dentate gyrus of more mature rats, PREGS, dehydroepiandrosterone sulfate and hydroxysteroid sulfatase inhibitors increase paired-pulse facilitation, without affecting basal glutamate release probability. This effect depends on activation of sigma(1)-like receptors and G(i/o) and involves a target in the release machinery that is downstream of residual Ca2+. These presynaptic actions of sulfated steroids could play important roles in physiological processes ranging from synapse maturation to learning and memory, as well as pathophysiological conditions such as fetal alcohol spectrum disorder. (c) 2007 Elsevier B.V. All rights reserved.
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