The Lateral Hypothalamus: An Uncharted Territory for Processing Peripheral Neurogenic Inflammation

Abstract

The roles of the hypothalamus and particularly the lateral hypothalamus (LH) in the regulation of inflammation and pain have been widely studied. The LH consists of a parasympathetic area that has connections with all the major parts of the brain. It controls the autonomic nervous system (ANS), regulates feeding behavior and wakeful cycles, and is a part of the reward system. In addition, it contains different types of neurons, most importantly the orexin neurons. These neurons, though few in number, perform critical functions such as inhibiting pain transmission and interfering with the reward system, feeding behavior and the hypothalamic pituitary axis (HPA). Recent evidence has identified a new role for orexin neurons in the modulation of pain transmission associated with several inflammatory diseases, including rheumatoid arthritis and ulcerative colitis. Here, we review recent findings on the various physiological functions of the LH with special emphasis on the orexin/receptor system and its role in mediating inflammatory pain.

Brainwide input-output architecture of paraventricular oxytocin and vasopressin neurons

“…As an integrative hub of peripheral sensory information, the LHA serves as a critical homeostatic regulator in the central nervous system. The complex cytoarchitecture of the LHA includes a diverse GABAergic neuronal population, providing a potential source of local inhibition to Oxt PVN neurons 37,38 . LHA inhibitory signaling may therefore function as an upstream regulator of Oxt synthesis and release from the paraventricular hypothalamic system.…”

“…Previous electrophysiological mapping of inputs to paraventricular neurons supports the existence of numerous proximal hypothalamic contacts, including from local GABAergic neurons [32][33][34]48 . Considering the heterogeneity of cell types in the lateral hypothalamus, more work is needed to understand what hypothalamic cells project to oxytocin neurons and how their activation might alter or regulate oxytocin neuronal firing 49 . One possibility supported by lesion and stimulation studies is that more proximal regions such as limbic nuclei (e.g., septum, amygdala, subiculum) can control oxytocin release through feed-forward inhibition from local hypothalamic GABAergic neurons 48,50 .…”

Cocaine-induced neural adaptations in the lateral hypothalamic melanin-concentrating hormone neurons and the role in regulating rapid eye movement sleep after withdrawal

“…By contrast, samples showed low levels of genes expressed by other cell types in LH ( Fig. 1d ; 57 – 59 ). These results suggest the specificity of the cell sampling.…”

Coherent activity at three major lateral hypothalamic neural outputs controls the onset of motivated behavior responses

“…The LH is a central nucleus that connects many brain regions that orchestrates vital behaviours (Bonnavion et al, 2016;Fakhoury et al, 2020). It is the central brain region of an interconnected network that includes the DRN, VTA and the LHb, which all have important functions in reward and sensory processing, arousal, and motivation (Bonnavion et al, 2016;Proulx et al, 2014;Nakamura, 2013…”