Astrocytes modulate a postsynaptic NMDA-GABAA-receptor crosstalk in hypothalamic neurosecretory neurons

Evgeniy S. Potapenko, Vinicia Campana Biancardi, Yiqiang Zhou, Javier Eduardo Stern

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

A dynamic balance between the excitatory and inhibitory neurotransmitters glutamate and GABA is critical for maintaining proper neuronal activity in the brain. This balance is partly achieved via presynaptic interactions between glutamatergic and GABAAergic synapses converging into the same targets. Here, we show that in hypothalamic magnocellular neurosecretory neurons (MNCs), a direct crosstalk between postsynaptic NMDA receptors (NMDARs) and GABAA receptors (GABAARs) contributes to the excitatory/inhibitory balance in this system. We found that activation of NMDARs by endogenous glutamate levels controlled by astrocyte glutamate transporters, evokes a transient and reversible potentiation of postsynaptic GABAARs. This inter-receptor crosstalk is calcium-dependent and involves a kinase-dependent phosphorylation mechanism, but does not require nitric oxide as an intermediary signal. Finally, we found the NMDAR-GABAAR crosstalk to be blunted in rats with heart failure, a pathological condition in which the hypothalamic glutamate-GABA balance is tipped toward an excitatory predominance. Together, our findings support a novel form of glutamate-GABA interactions in MNCs, which involves crosstalk between NMDA and GABAA postsynaptic receptors, whose strength is controlled by the activity of local astrocytes. We propose this inter-receptor crosstalk to act as a compensatory, counterbalancing mechanism to dampen glutamate-mediated overexcitation. Finally, we propose that an uncoupling between NMDARs and GABAARs may contribute to exacerbated neuronal activity and, consequently, sympathohumoral activation in such disease conditions as heart failure.

Original languageEnglish (US)
Pages (from-to)631-640
Number of pages10
JournalJournal of Neuroscience
Volume33
Issue number2
DOIs
StatePublished - Jan 9 2013

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GABA-A Receptors
N-Methyl-D-Aspartate Receptors
Astrocytes
Glutamic Acid
Neurons
gamma-Aminobutyric Acid
Heart Failure
Amino Acid Transport System X-AG
N-Methylaspartate
Synapses
Neurotransmitter Agents
Nitric Oxide
Phosphotransferases
Phosphorylation
Calcium
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Astrocytes modulate a postsynaptic NMDA-GABAA-receptor crosstalk in hypothalamic neurosecretory neurons. / Potapenko, Evgeniy S.; Biancardi, Vinicia Campana; Zhou, Yiqiang; Stern, Javier Eduardo.

In: Journal of Neuroscience, Vol. 33, No. 2, 09.01.2013, p. 631-640.

Research output: Contribution to journalArticle

Potapenko, Evgeniy S. ; Biancardi, Vinicia Campana ; Zhou, Yiqiang ; Stern, Javier Eduardo. / Astrocytes modulate a postsynaptic NMDA-GABAA-receptor crosstalk in hypothalamic neurosecretory neurons. In: Journal of Neuroscience. 2013 ; Vol. 33, No. 2. pp. 631-640.
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