Role of lateral hypothalamus in two aspects of attention in associative learning

Abstract

Orexin (hypocretin) and melanin-concentrating hormone (MCH) neurons are unique to the lateral hypothalamic (LH) region, but project throughout the brain. These cell groups have been implicated in a variety of functions, including reward learning, responses to stimulants, and the modulation of attention, arousal and the sleep/wakefulness cycle. Here, we examined roles for LH in two aspects of attention in associative learning shown previously to depend on intact function in major targets of orexin and MCH neurons. In experiments 1 and 2, unilateral orexin-saporin lesions of LH impaired the acquisition of conditioned orienting responses (ORs) and bilaterally suppressed FOS expression in the amygdala central nucleus (CeA) normally observed in response to food cues that provoke conditioned ORs. Those cues also induced greater FOS expression than control cues in LH orexin neurons, but not in MCH neurons. In experiment 3, unilateral orexin-saporin lesions of LH eliminated the cue associability enhancements normally produced by the surprising omission of an expected event. The magnitude of that impairment was positively correlated with the amount of LH damage and with the loss of orexin neurons in particular, but not with the loss of MCH neurons. We suggest that the effects of the LH orexin-saporin lesions were mediated by their effect on information processing in the CeA, known to be critical to both behavioral phenomena examined here. The results imply close relations between LH motivational amplification functions and attention, and may inform our understanding of disorders in which motivational and attentional impairments co-occur.

Deep brain stimulation for obesity: past, present, and future targets

“…80,103 Recent rodent studies have unveiled novel downstream effects of ONs. The amygdala is the prime target of the LHA ONs, and the stria terminalis accounts for much of the connectivity between the amygdala and the VMH.…”

“…The amygdala is the prime target of the LHA ONs, and the stria terminalis accounts for much of the connectivity between the amygdala and the VMH. 8,103 Findings in many animal models have implicated this major pathway in the valuation of highly palatable foods. 97,103 Certain neuropeptides of the ONs, such as orexins, have also been shown to be linked to drug seeking and addiction, including food addictions that contribute to obesity.…”

“…103 Another major modulatory nucleus of thalamocortical projections to and from the OFC is the inferior thalamic peduncle, which lies in close proximity to the stria terminalis and has been shown to elicit behavioral modifications in patients who have had DBS of the inferior thalamic peduncle for treating OCD.…”

“…80,97,103 In addition to the robust connectivity between the LHA and the limbic system, data supporting it as a DBS target include the modulatory effects of DBS on the resting metabolic rate in patients, 104 the recent discovery of amino acid-sensing pathways that connect the stomach to the LHA, 97 and the discovery of obesity-related genes expressed exclusively by ONs in the LHA. 103 Because the ONs of the LHA control diet-induced thermogenesis, reward circuits, energy homeostasis, and satiety, 80 the LHA continues to be the target of choice for addressing obesity due to metabolic dysregulation (in peripheral and central areas), genetics, or food addiction.…”

A presença do hormônio concentrador de melanina no ovário no ciclo reprodutivo de ratas<i> Sprague-Dawley</i>.

“…Classicamente descrito como um peptídeo com função no controle da pigmentação de peixes teleósteos, em antagonismo com o -MSH (Kawauchi et al, 1983;Mizusawa et al, 2012), atualmente já se conhece diversas funções atribuídas ao MCH, como ingestão alimentar e regulação homeostática (Qu et al, 1996;Flier, Maratos-Flier, 1998), influência no ciclo vigília-sono (Verret et al, 2003;Tsunematsu et al, 2014), aprendizado e memória (Monzon et al, 1999;Sherwood et al, 2012), modulação da atenção (Wheeler et al, 2014), regulação sensorial de pistas olfatórias (Adams et al, 2011), integração da resposta ao stress e ansiedade (Baker, Bird, Buckingham, 1985;Borowsky et al, 2002), além da integração do balanço energético e função reprodutiva (Williamson-Hughes, Grove, Smith, 2005;Naufahu, Cunliffe, Murray, 2013). Assim, o MCH funciona como um neuromodulador em diversas funções (Nahon et al, 1993).…”