Kelley and colleagues have studied a pathway from the nucleus accumbens to the LHA. Such a connection was early demonstrated with tracing techniques.73,74 Subsequent studies revealed that GABAergic spiny projection neurons in the shell region provide a diffuse innervation of the LHA in its entire rostrocaudal length.181 (In contrast, the accumbal core region supplies terminals only in the LHA region bordering on the entopeduncular nucleus).182 When glutamatergic excitation is blocked in the shell region, animals respond with increased food intake.183 This behaviour was not expressed when the LHA was simultaneously silenced with GABAergic stimulation. Moreover, under these circumstances, c-Fos is also induced in Hcrt neurons, but not in MCH neurons.184, 185 These results indicate that the accumbens-LHA projection negatively regulates activity in the Hcrt system. Such a pathway has been proposed to provide an indirect route for the cortex (which projects heavily to the nucleus accumbens) in inhibiting LHA-mediated feeding when competing stimuli appear.186 However, the data do not exclude the involvement of indirect connections. The numerous parallel direct and indirect pathways connecting the LHA with e.g. the SCh, VLPO and DMH (reviewed above) serve as a reminder that extensive feedback links often contribute in the fine-tuning of Hcrt-related behaviour.
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