Metabolic cues impact non‐oscillatory intergeniculate leaflet and ventral lateral geniculate nucleus: standard versus high‐fat diet comparative study

• Published in: The Journal of physiology Vol. 601; no. 5; pp. 979 - 1016
• Main Authors: Jeczmien‐Lazur, Jagoda S., Sanetra, Anna M., Pradel, Kamil, Izowit, Gabriela, Chrobok, Lukasz, Palus‐Chramiec, Katarzyna, Piggins, Hugh D., Lewandowski, Marian H.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.03.2023
• Subjects: anorexigenic peptides; Arousal; Cholecystokinin; Cholecystokinin - metabolism; circadian clock; Circadian rhythm; Circadian Rhythm - physiology; Circadian rhythms; Comparative studies; Cues; Diet, High-Fat; electrophysiology; Energy balance; Entrainment; Food intake; food‐intake peptides; Geniculate Bodies - physiology; Ghrelin; Ghrelin - metabolism; Glucagon; glucagon‐like peptide 1; High fat diet; Homeostasis; Hybridization; infra‐slow oscillatory activity; intergeniculate leaflet; Lateral geniculate nucleus; Metabolism; multi‐channel recordings; multi‐electrode arrays; Neurons; orexigenic peptides; orexin A; Orexins; Orexins - metabolism; Oscillations; oxyntomodulin; Oxyntomodulin - metabolism; peptide YY; Peptide YY - metabolism; Peptides; Photoreceptors; Suprachiasmatic Nucleus - metabolism; Thalamus; ventral lateral geniculate nucleus; Visual system; orexigenic peptides; cholecystokinin; glucagon-like peptide 1; multi-channel recordings; circadian clock; intergeniculate leaflet; oxyntomodulin; ghrelin; orexin A; electrophysiology; ventral lateral geniculate nucleus; anorexigenic peptides; high-fat diet; food-intake peptides; multi-electrode arrays; infra-slow oscillatory activity; peptide YY; thalamus
• ISSN: 0022-3751; 1469-7793; 1469-7793
• DOI: 10.1113/JP283757

The intergeniculate leaflet and ventral lateral geniculate nucleus (IGL/VLG) are subcortical structures involved in entrainment of the brain's circadian system to photic and non‐photic (e.g. metabolic and arousal) cues. Both receive information about environmental light from photoreceptors, exhibit infra‐slow oscillations (ISO) in vivo, and connect to the master circadian clock. Although current evidence demonstrates that the IGL/VLG communicate metabolic information and are crucial for entrainment of circadian rhythms to time‐restricted feeding, their sensitivity to food intake‐related peptides has not been investigated yet. We examined the effect of metabolically relevant peptides on the spontaneous activity of IGL/VLG neurons. Using ex vivo and in vivo electrophysiological recordings as well as in situ hybridisation, we tested potential sensitivity of the IGL/VLG to anorexigenic and orexigenic peptides, such as cholecystokinin, glucagon‐like peptide 1, oxyntomodulin, peptide YY, orexin A and ghrelin. We explored neuronal responses to these drugs during day and night, and in standard vs. high‐fat diet conditions. We found that IGL/VLG neurons responded to all the substances tested, except peptide YY. Moreover, more neurons responded to anorexigenic drugs at night, while a high‐fat diet affected the IGL/VLG sensitivity to orexigenic peptides. Interestingly, ISO neurons responded to light and orexin A, but did not respond to the other food intake‐related peptides. In contrast, non‐ISO cells were activated by metabolic peptides, with only some being responsive to light. Our results show for the first time that peptides involved in the body's energy homeostasis stimulate the thalamus and suggest functional separation of the IGL/VLG cells. Key points The intergeniculate leaflet and ventral lateral geniculate nucleus (IGL/VLG) of the rodent thalamus process various signals and participate in circadian entrainment. In both structures, cells exhibiting infra‐slow oscillatory activity as well as non‐rhythmically firing neurons being observed. Here, we reveal that only one of these two groups of cells responds to anorexigenic (cholecystokinin, glucagon‐like peptide 1 and oxyntomodulin) and orexigenic (ghrelin and orexin A) peptides. Neuronal responses vary depending on the time of day (day vs. night) and on the diet (standard vs. high‐fat diet). Additionally, we visualised receptors to the tested peptides in the IGL/VLG using in situ hybridisation. Our results suggest that two electrophysiologically different subpopulations of IGL/VLG neurons are involved in two separate functions: one related to the body's energy homeostasis and one associated with the subcortical visual system. figure legend (1) Sprague–Dawley rats were fed ad libitum with control (CD) or a high‐fat (HFD) chow in a 12:12 h light–dark cycle. (2) The subject of the study was the thalamic intergeniculate leaflet (IGL) and ventral lateral geniculate nucleus (VLG) showing spontaneous infra‐slow oscillatory (ISO) or non‐oscillatory (non‐ISO) activity. (3) Neuronal activity of the IGL and VLG was recorded using ex vivo and in vivo electrophysiological techniques. (4) Anorexigenic (in green) and orexigenic (in red) peptides such as cholecystokinin (CCK), glucagon‐like peptide 1 (GLP‐1), oxyntomodulin (OXM), peptide YY (pYY), orexin A (OXA) and ghrelin (Ghrl) were administered during IGL/VLG recordings. (5) We found that non‐ISO neurons of the IGL/VLG responded with an increase in firing rate to all the substances tested, except peptide YY. The amplitude (marked with arrows) and frequency of responses (marked with <, >) varied depending on the diet and the phase of the day. (6) In situ hybridisation was performed on IGL/VLG‐containing brain sections to visualise receptors to the tested peptides.