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1.
Proc Natl Acad Sci U S A ; 119(48): e2201783119, 2022 11 29.
Article En | MEDLINE | ID: mdl-36413500

Trimethylglycine, or betaine, is an amino acid derivative found in diverse organisms, from bacteria to plants and animals, with well-established functions as a methyl donor and osmolyte in all cells. In addition, betaine is found in the nervous system, though its function there is not well understood. Here, we show that betaine is synthesized in the nervous system of the nematode worm, Caenorhabditis elegans, where it functions in the control of different behavioral states. Specifically, we find that betaine can be produced in a pair of interneurons, the RIMs, and packed into synaptic vesicles by the vesicular monoamine transporter, CAT-1, expressed in these cells. Mutant animals defective in betaine synthesis are unable to control the switch from local to global foraging, a phenotype that can be rescued by restoring betaine specifically to the RIM neurons. These effects on behavior are mediated by a newly identified betaine-gated chloride channel, LGC-41, which is expressed broadly in the navigation circuit. These results implicate neuronally produced betaine as a neuromodulator in vivo and suggest a potentially similar role for betaine in nervous systems of other animals.


Caenorhabditis elegans Proteins , Ligand-Gated Ion Channels , Animals , Ligand-Gated Ion Channels/genetics , Betaine/pharmacology , Betaine/metabolism , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Nervous System/metabolism
2.
Proc Natl Acad Sci U S A ; 118(39)2021 09 28.
Article En | MEDLINE | ID: mdl-34556572

Light provides the primary signal for entraining circadian rhythms to the day/night cycle. In addition to rods and cones, the retina contains a small population of photosensitive retinal ganglion cells (pRGCs) expressing the photopigment melanopsin (OPN4). Concerns have been raised that exposure to dim artificial lighting in the evening (DLE) may perturb circadian rhythms and sleep patterns, and OPN4 is presumed to mediate these effects. Here, we examine the effects of 4-h, 20-lux DLE on circadian physiology and behavior in mice and the role of OPN4 in these responses. We show that 2 wk of DLE induces a phase delay of ∼2 to 3 h in mice, comparable to that reported in humans. DLE-induced phase shifts are unaffected in Opn4-/- mice, indicating that rods and cones are capable of driving these responses in the absence of melanopsin. DLE delays molecular clock rhythms in the heart, liver, adrenal gland, and dorsal hippocampus. It also reverses short-term recognition memory performance, which is associated with changes in preceding sleep history. In addition, DLE modifies patterns of hypothalamic and cortical cFos signals, a molecular correlate of recent neuronal activity. Together, our data show that DLE causes coordinated realignment of circadian rhythms, sleep patterns, and short-term memory process in mice. These effects are particularly relevant as DLE conditions-due to artificial light exposure-are experienced by the majority of the populace on a daily basis.


Circadian Rhythm , Light , Memory, Short-Term/physiology , Retinal Ganglion Cells/physiology , Rod Opsins/physiology , Sleep/physiology , Animals , Female , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Retinal Ganglion Cells/cytology
3.
Sci Rep ; 10(1): 20680, 2020 11 26.
Article En | MEDLINE | ID: mdl-33244132

Body temperature is an important physiological parameter in many studies of laboratory mice. Continuous assessment of body temperature has traditionally required surgical implantation of a telemeter, but this invasive procedure adversely impacts animal welfare. Near-infrared thermography provides a non-invasive alternative by continuously measuring the highest temperature on the outside of the body (Tskin), but the reliability of these recordings as a proxy for continuous core body temperature (Tcore) measurements has not been assessed. Here, Tcore (30 s resolution) and Tskin (1 s resolution) were continuously measured for three days in mice exposed to ad libitum and restricted feeding conditions. We subsequently developed an algorithm that optimised the reliability of a Tskin-derived estimate of Tcore. This identified the average of the maximum Tskin per minute over a 30-min interval as the optimal way to estimate Tcore. Subsequent validation analyses did however demonstrate that this Tskin-derived proxy did not provide a reliable estimate of the absolute Tcore due to the high between-animal variability in the relationship between Tskin and Tcore. Conversely, validation showed that Tskin-derived estimates of Tcore reliably describe temporal patterns in physiologically-relevant Tcore changes and provide an excellent measure to perform within-animal comparisons of relative changes in Tcore.


Body Temperature/physiology , Skin/physiopathology , Animals , Body Temperature Regulation/physiology , Diet Therapy/methods , Feeding Methods , Hot Temperature , Mice , Mice, Inbred C57BL , Reproducibility of Results , Thermography/methods
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