Retrograde Regulation of GABA Transmission by the Tonic Release of Oxytocin and Endocannabinoids Governs Postsynaptic Firing
Journal of Neuroscience. 2007-02-07; 27(6): 1325-1333
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1. J Neurosci. 2007 Feb 7;27(6):1325-33.
Retrograde regulation of GABA transmission by the tonic release of oxytocin and
endocannabinoids governs postsynaptic firing.
Oliet SH(1), Baimoukhametova DV, Piet R, Bains JS.
(1)Institut National de la Santé et de la Recherche Médicale, Unité 862,
Université Victor Segalen Bordeaux 2, Bordeaux 33077, France.
The probability of neurotransmitter release at the nerve terminal is an important
determinant of synaptic efficacy. At some central synapses, the postsynaptic, or
target, neuron determines neurotransmitter release probability (P(r)) at the
presynaptic terminal. The mechanisms responsible for this target-cell dependent
control of P(r) have not been elucidated. Using whole-cell patch-clamp recordings
from magnocellular neurosecretory cells in the paraventricular and supraoptic
nuclei of the hypothalamus, we demonstrate that inhibitory, GABA synapses
specifically onto oxytocin (OT)-producing neurosecretory cells exhibit a low P(r)
that is relatively uniform at multiple synapses onto the same cell. This low P(r)
results from a two-step process that requires the tonic release of OT from the
postsynaptic cell. The ambient extracellular levels of neuropeptide are
sufficient to activate postsynaptic OT receptors and trigger the Ca2+-dependent
production of endocannabinoids, which act in a retrograde manner at presynaptic
cannabinoid CB1 receptors to decrease GABA release. The functional consequence of
this tonic inhibition of GABA release is that all inhibitory inputs facilitate
uniformly when activated at high rates of activity. This causes inhibition in the
postsynaptic cell that is sufficiently powerful to disrupt firing. Blockade of
CB1 receptors increases P(r) at these synapses, resulting in a rapid depression
of IPSCs at high rates of activity, thereby eliminating the ability of afferent
inputs to inhibit postsynaptic firing. By playing a deterministic role in GABA
release at the afferent nerve terminal, the postsynaptic OT neuron effectively
filters synaptic signals and thereby modulates its own activity patterns.
PMID: 17287507 [Indexed for MEDLINE]