Taste circuits in hypothalamus

描述（由申请人提供）：肥胖是由能量摄入和能量消耗之间的持续不平衡引起的。这种普遍的健康问题增加了心血管疾病、2型糖尿病和某些类型癌症的风险。有人认为，过度驱动的大脑奖励回路，高食物的适口性过度刺激，可能是这种情况越来越普遍的基础。下丘脑在能量平衡中起着核心作用。外侧下丘脑（LH）被认为参与了信号和/或响应食物适口性及其强化作用的回路。众所周知，在啮齿动物中，来自脑干的味觉传入直接到达LH，但对味觉如何调节LH回路知之甚少。虽然灵长类动物的味觉系统没有这样的直接输入LH，许多潜在的适口性和食物奖励电路的机制无疑是可比的。由于啮齿动物是目前用于探索能量平衡和肥胖的大脑系统的主要模型系统，因此了解直接味觉输入如何调节大鼠中的这些回路非常重要。我们有数据显示，刺激外周味觉神经之一激活LH中含有摄食刺激肽的神经元（即，食欲素），而不是在同一区域的神经元含有不同的摄食刺激肽（MCH）。这表明食欲素神经元系统对味觉输入有选择性反应，并且与MCH系统相比，在涉及适口性的回路中更重要。我们提出的实验将确定是否所有的味觉神经产生这些相同的影响，不同的LH神经元群体，如果解剖连接与味觉轴突在LH仅限于食欲素神经元，如果两个不同的肽系统在LH表现出不同程度的下降调制输入到味觉区引起的味觉输入到LH。这些研究的结果将进一步加深我们对食物的味道如何影响大脑复杂的相互作用的控制饮食，体重和能量消耗的回路的理解。

DESCRIPTION (provided by applicant): Obesity results from a sustained imbalance between energy intake and energy expenditure. This widespread health problem increases the risk of cardiovascular disease, type 2 diabetes, and certain types of cancers. It has been suggested that overdriven brain reward circuitry, hyperstimulated by high food palatability, may underlie the growing prevalence of this condition. The hypothalamus plays a central role in energy balance. The lateral hypothalamus (LH) is believed to participate in circuits that signal and/or respond to food palatability and its reinforcing effects. It is known that in rodents, gustatory afferents from the brainstem reach the LH directly, but very little is known about how taste modulates LH circuits. Although the primate gustatory system does not have such direct input to the LH, many of the mechanisms underlying palatability and food reward circuitry are undoubtedly comparable. Because the rodent is the major model system currently in use for exploring brain systems of energy balance and obesity, it is very important to understand how direct taste input regulates these circuits in rats. We have data showing that stimulation of one of the peripheral taste nerves activates neurons in the LH that contain a feeding-stimulating peptide (i.e., orexin) but not neurons in the same region containing a different feeding-stimulating peptide (MCH). This suggests that the orexin neuron system is selectively responsive to gustatory input, and compared to the MCH system, is more important in circuits involving palatability. Our proposed experiments will determine if all taste nerves produce these same effects on different LH neuron populations, if anatomical connections with gustatory axons in the LH are limited to orexin neurons only, and if the two different peptide systems in the LH demonstrate differential degrees of descending modulatory input to the gustatory region giving rise to the taste input to the LH. The results of these studies will further our understanding of how the taste of food influences the brain's complex, interacting circuitry controlling eating, body weight and energy expenditure.