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.

Every living organism has two biological driving forces: the need to reproduce and the need to feed. The need to feed is not merely a balancing act between energy expended and caloric intake. Ingestion of calorically sufficient and palatable foods is mediated by the central nervous system and its subsidiaries. The hypothalamus is the main mediator of homeostasis and the lateral hypothalamus (LH) is of particular interest in regards to feeding. Glutamate (Glu) is present throughout the mammalian brain and within the LH Glu influences feeding. Previously ionotropic glutamate receptors were shown to facilitate this response. Here, we have attempted to identify and demonstrate that metabotropic glutamate receptors (mGluRs) also influence feeding. Intracranial injections of drugs either activating or blocking mGluRs increases or suppresses food intake. These effects were limited to the LH, effects seen in different brain regions can be attributed to the diffusion of the agonist to the LH. Although blockage of mGluRs during a time period of high extracelluar glutamate concentration is ineffective in suppressing feeding, we discuss possible alternative mechanisms for these observations. None the less our findings suggest that group I mGluRs are involved in feeding.

Behavioral learning involves modifications to relevant synapses at the neural level, a process known as synaptic plasticity - the ability of the strength of the connections between synapses to change. These changes at the synaptic level are believed to underlie learning and memory. Perceptual learning (PL) is a type of learning that refers to a long lasting improvement in sensory perception as a result of practice or training. PL has been found for a variety of visual tasks, this type of learning also requires synaptic plasticity. However, PL studies typically require a significant amount of training, and concentrate on isolating a single mechanism, leading to great specificity of learning on the trained task. This focus on this specificity has defined the field, but is not representative of ecological conditions. Combining many features is more representation of nature, and recent research suggests this type of training leads to more broad based perceptual benefits. This dissertation will investigate the links between the rules of plasticity at the cellular level and behavior in both a single mechanism, using exposure-based learning, and by combining several PL approaches into a video game framework.

Using the single PL mechanism, exposure-based learning, does not significantly alter behavior on a contrast discrimination task after limited training. Using an integrative approach that combines many perceptual learning mechanisms, including attention, reinforcement, multisensory stimuli, and multi-stimulus dimensions, broad-based benefits of vision were found in a healthy adult population. These results were extended into a highly specialized population, college baseball players. The improvements transferred not only to laboratory tests of vision, but also to improved offensive performance on the baseball field.

Overall, these results give evidence that rules of synaptic plasticity have efficacy when applied at the behavioral level using PL mechanisms. Work remains on establishing optimal training procedures and relating the training induced benefits to the underlying neural mechanisms. Integrating PL approaches that use longer training paradigms produce robust improvements to vision. These findings provide an exciting potential for PL based video-game training to be used as a diagnosis tool and therapeutic intervention to a variety of visual conditions.