Remote control of glucose-sensing neurons to analyze glucose metabolism

Abstract

The central nervous system relies on a continual supply of glucose, and must be able to detect glucose levels and regulate peripheral organ functions to ensure that its energy requirements are met. Specialized glucose-sensing neurons, first described half a century ago, use glucose as a signal and modulate their firing rates as glucose levels change. Glucose-excited neurons are activated by increasing glucose concentrations, while glucose-inhibited neurons increase their firing rate as glucose concentrations fall and decrease their firing rate as glucose concentrations rise. Glucose-sensing neurons are present in multiple brain regions and are highly expressed in hypothalamic regions, where they are involved in functions related to glucose homeostasis. However, the roles of glucose-sensing neurons in healthy and disease states remain poorly understood. Technologies that can rapidly and reversibly activate or inhibit defined neural populations provide invaluable tools to investigate how specific neural populations regulate metabolism and other physiological roles. Optogenetics has high temporal and spatial resolutions, requires implants for neural stimulation, and is suitable for modulating local neural populations. Chemogenetics, which requires injection of a synthetic ligand, can target both local and widespread populations. Radio- and magnetogenetics offer rapid neural activation in localized or widespread neural populations without the need for implants or injections. These tools will allow us to better understand glucose-sensing neurons and their metabolism-regulating circuits.

Glutamate receptor antagonist suppresses the activation of nesfatin-1 neurons following refeeding or glucose administration

“…The hypothalamus plays an important role in regulating food intake and glucose homeostasis (33). Glucose is the primary fuel for the brain and enters the CNS with the high affinity glucose transporter (GLUT) type 1 (2). Glucosensitive and glucoresponsive neurons are found in the hypothalamic nuclei and participate in glucose homeostasis (33).…”

Neonatal Hypoglycemia and Brain Vulnerability

“…As glucose concentrations decrease, GI neurons are excited, whereas GE neurons decrease their activity (37). Glucose sensing neurons are mainly situated in the hypothalamic nuclei, the prefrontal cortex, the hippocampus, the paraventricular thalamus, and the amygdala (38)(39)(40).…”

Neuromodulation of metabolic functions: from pharmaceuticals to bioelectronics to biocircuits

“…This network senses circulating hormones and regulates metabolisms [52]. Stimulation of these circuits allows for exogenous control of weight gain [74] and glucose metabolism [5]. Selective modulation of these distinct neuronal populations provides access to regain control of systemic metabolic functions.…”

“…2), which regulates appetite and energy expenditure, can ameliorate symptoms of diabetes in rodent models [74]. Electrical stimulation of glucose sensing neurons in the CNS [5] can control systemic glucose levels. Striatal dopamine also can regulate systemic glucose metabolism; and DBS in patients with diabetes results in increased insulin production and enhanced glycemic control following stimulation of the basal ganglia [55].…”

“…Vagus nerve stimulation (VNS, Fig. 1c) could likely reduce the global burden of diseases [47], primarily by ameliorating the symptoms of cardiovascular diseases [5]. Additionally, vagal efferent fibers innervate the pancreas to control the excitability of β-cells, thereby facilitating their release of insulin [2, 72].…”