Plasticity in fast synaptic inhibition of adult oxytocin neurons caused by switch in GABA(A) receptor subunit expression.
We found that magnocellular oxytocin neurons in adult female rats exhibit an endogenous GABA(A) receptor subunit switch around parturition: a decrease in alpha1:alpha2 subunit mRNA ratio correlated with a decrease in allopregnanolone potentiation and increase in decay time constant of the GABA(A) receptor-mediated IPSCs in these cells. The causal relationship between changes in alpha1:alpha2 mRNA ratio and the ion channel kinetics was confirmed using in vitro antisense deletion. Further, GABA(A) receptors exhibited a tonic inhibitory influence upon oxytocin release in vivo, and allopregnanolone helped to restrain oxytocin neuron in vitro firing only before parturition, when the alpha1:alpha2 subunit mRNA ratio was still high. Such observations provide evidence for the physiological significance of GABA(A) receptor subunit heterogeneity and plasticity in the adult brain.
Brussaard
A B
AB
Membrane Physiology Section, Research Institute Neurosciences, Vrije Universiteit Amsterdam, The Netherlands.
Kits
K S
KS
Baker
R E
RE
Willems
W P
WP
Leyting-Vermeulen
J W
JW
Voorn
P
P
Smit
A B
AB
Bicknell
R J
RJ
Herbison
A E
AE
D000818:Animals; D004553:Electric Conductivity; D004594:Electrophysiology; D005260:Female; D018757:GABA Modulators / Q000494:pharmacology; D007743:Labor, Obstetric / Q000378:metabolism; D009433:Neural Inhibition / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010121:Oxytocin / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011280:Pregnanolone / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013495:Supraoptic Nucleus / Q000166:cytology / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors
D018757:GABA Modulators; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D010121:Oxytocin; D011280:Pregnanolone