Forebrain glutamatergic neurons mediate leptin action on depression-like behaviors and synaptic depression

• DOI: 10.1038/tp.2012.9
• Publication Date: 2012-02-21T16:49:19Z
• Authors: M Guo; Y Lu; J C Garza; Y Li; S C Chua; W Zhang; B Lu; X-Y Lu
• Keywords: Forebrain; Leptin receptor

The glutamatergic system has been implicated in the pathophysiology of depression and mechanism action antidepressants. Leptin, an adipocyte-derived hormone, antidepressant-like properties. However, functional role leptin receptor (Lepr) signaling neurons remains to be elucidated. In this study, we generated conditional knockout mice which long form Lepr was ablated selectively located forebrain structures, including hippocampus prefrontal cortex (Lepr cKO). cKO exhibit normal growth body weight. Behavioral characterization reveals depression-like behavioral deficits, anhedonia, despair, enhanced learned helplessness social withdrawal, with no evident signs anxiety. addition, loss facilitates N-methyl-D-aspartate (NMDA)-induced hippocampal long-term synaptic (LTD), whereas conventional LTD or potentiation (LTP) not affected. facilitated induction requires activation NMDA GluN2B (NR2B) subunit as it completely blocked by a selective antagonist. Moreover, are highly sensitive effects antagonist but resistant leptin. These results support important roles for regulating depression-related behaviors modulating excitatory strength, suggesting possible association between manifestation depression.