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Lateral hypothalamic orexin glucose-inhibited neurons may regulate reward-based feeding by modulating glutamate transmission in the ventral tegmental area.

Abstract：

:Glucose inhibits ∼60% of lateral hypothalamic (LH) orexin neurons. Fasting increases the activation of LH orexin glucose-inhibited (GI) neurons in low glucose. Increases in spontaneous glutamate excitatory postsynaptic currents (sEPSCs) onto putative VTA DA neurons in low glucose are orexin dependent (Sheng et al., 2014). VTA DA neurons modulate reward-based feeding. We tested the hypothesis that increased activation of LH orexin-GI neurons in low glucose increases glutamate signaling onto VTA DA neurons and contributes to reward-based feeding in food restricted animals. N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) currents on putative VTA DA neurons were measured using whole cell voltage clamp recording in horizontal brain slices containing the LH and VTA. Decreased glucose increased the NMDA receptor current for at least one hour after returning glucose to basal levels (P < 0.05; N = 8). The increased current was blocked by an orexin 1 receptor antagonist (P < 0.05; N = 5). Low glucose caused a similar persistent enhancement of AMPA receptor currents (P < 0.05; N = 7). An overnight fast increased the AMPA/NMDA receptor current ratio, an in vivo index of glutamate plasticity, on putative VTA DA neurons. Conditioned place preference (CPP) for palatable food was measured during LH dialysis with glucose. CPP score was negatively correlated with increasing LH glucose (P < 0.05; N = 20). These data suggest that increased activation of LH orexin-GI neurons in low glucose after weight loss, leads to enhanced glutamate signaling on VTA DA neurons, increases the drive to eat rewarding food, and may contribute to weight regain.

journal_name

Brain Res

journal_title

Brain research

authors

Teegala SB,Sheng Z,Dalal MS,Hirschberg PR,Beck KD,Routh VH

doi

10.1016/j.brainres.2018.05.025

subject

Has Abstract

pub_date

2020-03-15 00:00:00

pages

145808

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(18)30282-8

journal_volume

1731

pub_type

杂志文章

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Lateral hypothalamic orexin glucose-inhibited neurons may regulate reward-based feeding by modulating glutamate transmission in the ventral tegmental area.