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Analysis of Ipsilateral Functional and Anatomical Associations Between the Nucleus Accumbens Shell and the Lateral Hypothalamus: Relations With Feeding Behaviors

  • Author(s): Urstadt, Kevin
  • Advisor(s): Stanley, Glenn
  • et al.
Abstract

The nucleus accumbens shell (AcbSh) and the lateral hypothalamus (LH) are associated in the control of feeding. Functional and anatomical evidence links these two areas in their control of food intake, and further studies implicate glutamate and GABA as major signaling factors in this circuit. However, it is unclear 1. whether inhibition of the LH decreases AcbSh-mediated intake in a behaviorally-specific manner, 2. if this behavioral specificity is regulated by an ipsilateral-only circuit, and 3. what neuron types send feedback signals from the LH to the AcbSh. In this dissertation, the background knowledge of these two areas and their roles in feeding and reward are reviewed. Then, in a series of studies, the three above issues are addressed. The AcbSh was inhibited by unilateral injection of muscimol or DNQX, and the LH was inhibited bilaterally, contralateral, or ipsilateral to the AcbSh injection site with D-AP5 or muscimol. Food intake and behaviors were monitored. Bilateral LH inhibition resulted in decreased AcbSh-mediated intake, but did so by inducing sleep. Contralateral LH inhibition had little effect on AcbSh mediated intake or behaviors, while ipsilateral LH inhibition decreased food intake by selective reducing feeding behavior only. In a separate group of rats, Fluorogold was iontophoretically injected into the AcbSh, and coronal sections with the LH were immunohistochemically stained for orexin, melanin-concentrating hormone (MCH), cocaine and amphetamine-regulated transcript (CART), nesfatin-1, vessicular GABA transporter (VGAT), vessicular glutamate transporters 2 and 3 (VGluT2 & VGluT3), glutamic acid decarboxylase (GAD67), and phospho-STAT3 (pSTAT3). LH neurons projecting to the AcbSh rarely were distributed in the ventrolateral LH, rarely co-localized with orexin, MCH, or pSTAT3 staining, occasionally co-localized with CART or VGluT3, and typically co-localized with nesfatin, VGAT, or GAD67. The body of evidence presented herein demonstrates a feeding-specific descending connection between the AcbSh and the LH, and with anatomical evidence suggests an inhibitory feedback circuit that may rely on decreasing food intake by acting on AcbSh sites that regulate aversive behaviors.

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