Astrocytes influence neurosecretory and presympathetic hypothalamic neurons via activation of extrasynaptic NMDARs negatively coupled to A‐type K+ channels
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Media type:
E-Article
Title:
Astrocytes influence neurosecretory and presympathetic hypothalamic neurons via activation of extrasynaptic NMDARs negatively coupled to A‐type K+ channels
Description:
We recently showed that activation of extrasynaptic NMDARs (eNMDARs) by ambient glutamate under astrocyte control, inhibited the voltage‐gated K+ current IA in non‐identified neurosecretory neurons. Here, we aimed to address i) whether the eNMDAR/IA coupling is present in identified neurosecretory vasopressin (VP) and PVN‐RVLM presympathetic neurons, ii) the biophysical properties of IA targeted by eNMDAR, and iii) the functional consequence of the eNMDAR/IA coupling on neuronal firing activity. Patch clamp recordings were obtained from identified eGFP‐VP SON and PVN‐RVLM neurons. We found that activation of eNMDAR following astrocyte glutamate transporter block (DHK 300 μM) inhibited IA in ~70% of VP and ~50% of PVN‐RVLM neurons (~30% and ~ 25% inhibition, respectively P<0.05) Activation of eNMDARs shifted IA voltage dependence of inactivation to more hyperpolarized membrane potentials (ΔV1/2 inactivation ~−20 mV). Finally, the eNMDAR/IA coupling strengthened neuronal input/output function (i.e., leftward shift, more firing at less stimulation). Collectively, our results show that activation of eNMDARs, both in neurosecretory and presympathetic neurons, inhibits IA function, enhancing in turn neuronal excitability. Thus, the eNMDAR/IA coupling stands as a functionally relevant target by which astrocytes influence hypothalamic neurohumoral outflow. Supported by RO1 HL 090948.