Role of G-proteins in the effects of leptin on pedunculopontine nucleus (PPN) neurons

BECK P; MAHAFFEY S; # URBANO FJ ; # GARCIA-RILL E # URBANO FJ & GARCIA-RILL E CONTRIBUTED EQUALLY AS LAST AUTHORS.

JOURNAL OF NEUROCHEMISTRY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2013 vol. 126 p. 705 - 714

0022-3042

----------FJ Urbano & E. Garcia-Rill contributed equally as last authors (see pdf)---------- The pedunculopontine nucleus (PPN), the cholinergic arm of the reticular activating system, regulates waking and rapid eye movement (REM) sleep. Here, we demonstrate immunohistochemical labeling of the leptin receptor signaling isoform in PPN neurons, and investigated the effects of G-protein modulation and the leptin triple antagonist (TA) on the action of leptin in the PPN. Whole-cell patch clamp recordings were performed in rat brainstem slices from 9-17 day old pups. Previous results showed that leptin caused a partial blockade of sodium (INa) and h-current (IH) in PPN neurons. TA (100 nM) reduced the blockade of INa (~50% reduction) and IH (~93% reduction) caused by leptin. Intracellular GDPβ (a G-protein inhibitor) significantly reduced the effect of leptin on INa(~60% reduction) but not on IH (~25% reduction). Intracellular GTPγS (a G-protein activator) reduced the effect of leptin on both INa (~80% reduction) and IH (~90% reduction). These results suggest that the effects of leptin on the intrinsic properties of PPN neurons are leptin receptor- and G-protein-dependent. We also found that leptin enhanced NMDA receptor-mediated responses in single neurons and in the PPN population as a whole, an effect blocked by TA. These experiments further strengthen the association between leptin dysregulation and sleep disturbances.