PT  - JOURNAL ARTICLE
AU  - Hao Huang
AU  - Anthony N. van den Pol
TI  - Rapid Direct Excitation and Long-Lasting Enhancement of NMDA Response by Group I Metabotropic Glutamate Receptor Activation of Hypothalamic Melanin-Concentrating Hormone Neurons
AID  - 10.1523/JNEUROSCI.2147-07.2007
DP  - 2007 Oct 24
TA  - The Journal of Neuroscience
PG  - 11560--11572
VI  - 27
IP  - 43
4099  - http://www.jneurosci.org/content/27/43/11560.short
4100  - http://www.jneurosci.org/content/27/43/11560.full
SO  - J. Neurosci.2007 Oct 24; 27
AB  - The effect of group I metabotropic glutamate receptor (mGluR1 and mGluR5) activation on identified melanin-concentrating hormone (MCH) neurons was studied using patch-clamp recording in hypothalamic slices from green fluorescent protein-expressing transgenic mice. S-3,5-dihydroxyphenylglycine (DHPG), a selective group I mGluR agonist, depolarized MCH cells and increased spike frequency. The mGluR-mediated depolarization was not blocked with tetrodotoxin but was significantly reduced by replacement of extracellular Na+ with Tris, by Ni2+ or the Na+/Ca2+ exchanger blocker KB-R7943, or with BAPTA in the pipette, consistent with a mechanism based on activation of the Na+/Ca2+ exchanger. DHPG also decreased potassium currents. DHPG-induced depolarization was reduced by either mGluR1 or mGluR5 antagonists, suggesting involvement of both receptor subtypes. DHPG-induced depolarization desensitized; blockade of mGluR1 prevented the desensitization. Group I mGluR activation enhanced NMDA-evoked currents; this enhancement was remarkably long lasting and could be blocked by protein kinase A or C blockers. DHPG potentiated electrically evoked NMDA receptor-mediated postsynaptic currents, and mGluR5 antagonists blocked this action. Group I mGluRs increased spontaneous EPSCs in MCH neurons, possibly by stimulation of nearby mGluR-expressing hypocretin neurons. We found no tonic activation of mGluRs. However, electrical stimulation produced a slow inward current, which could be blocked by group I mGluR antagonists, suggesting high, but not low, levels of synaptically released glutamate activated mGluRs. Together, group I mGluRs increase MCH neuron activity by multiple presynaptic and postsynaptic mechanisms, suggesting mGluRs may therefore play a role in hypothalamic signaling relating to MCH neuron modulation of food intake and energy metabolism.