Fig. 4. Leptin blunts the response of LHA orexin-GI neurons to decreased glucose.

A) Whole cell current-clamp recording from an LHA orexin-GI neuron in a brain slice. Leptin hyperpolarizes this orexin-GI neuron in 2.5 mM glucose (G) and reduces the action potential frequency and input resistance (IR). B) Representative traces of the voltage response to a constant hyper- polarizing current pulse under the conditions in (A). Leptin reversibly decreased IR in 2.5 mM glucose as indicated by a decrease in the voltage response. C) Data bars represent % change in membrane potential (MP) and IR of LHA orexin-GI neurons when leptin is added to 2.5 mM glucose. Leptin significantly hyperpolarized the MP of orexin-GI neurons by 2.4 ± 0.5% and decreased their IR by 7.9 ± 0.7% (n = 10). D) Whole cell current-clamp recording from an LHA orexin-GI neuron in a brain slice. Leptin attenuates the response of this orexin-GI neuron to 0.1 mM glucose. E) Representative traces of the voltage response to a constant hyperpolarizing current pulse under the conditions in (D). Leptin blunted the increase in IR as glucose decreased from 2.5 to 0.1 mM. F) Data bars represent the % change in MP or IR as glucose was lowered from 2.5 to 0.1 mM. Leptin significantly reduced the change in MP and IR normally associated with decreased glucose (n = 16). The effect of leptin on glucose sensitivity was blocked by the GABA A and B receptor antagonists, bicucculline (20 μM) and saclofen (100 μM) (n = 6). Data were analyzed by t-test (*P < 0.05; **P < 0.01). N values are indicated within bars.