Postsynaptic crosstalk between excitatory (NMDA) and inhibitory (GABAA) receptors in neurosecretory neurons of the hypothalamic supraoptic nucleus (SON)

The electrical activity of SON neurosecretory neurons is regulated by a glutamate (GLU) excitatory/GABA inhibitory synaptic balance, fine‐tuned by the activity of surrounding astrocytes. While presynaptic interactions between GABA and GLU inputs are well‐established, little is know about potential postsynaptic interactions between these opposing inputs. To address this problem, we obtained patch‐clamp recordins from SON neurons in brain slices. Focal application of the GABAA receptor agonist Muscimol (100 μM) induced an outward current (1105 ± 270 pA*sec) that was enhanced following simultaneous activation of NMDA receptors, either with NMDA (30 μM; ~90% increase, P<0.01, n=10) or following elevated ambient glutamate levels by blockade of glial GLT1 GLU transporters (500 μM DHK; ~75% increase, P<0.01, n=10). The enhanced GABAA receptor efficacy was blunted when [Ca2+]i was chelated with BAPTA (~80 % inhibition P<0.01). Ongoing experiments aim at elucidating the contribution of intracellular kinases/phosphatases to NMDA‐GABAA interactions. Our results support a Ca2+‐dependent postsynaptic crosstalk between NMDA and GABAA receptors. This crosstalk is influenced by astrocyte GLU transporters, and stands as an efficient homeostatic mechanism by which an increase in excitatory drive is compensated by a concomitant increase in GABAA inhibitory efficacy. Supported by NIH RO1 HL 090948.