Galanin inhibition of wake-active histaminergic neurons
Bibliographic record
Abstract
Histaminergic neurons are a population of wake-active neurons confined to the tuberomammillary nucleus (TMN) in the posterior hypothalamus. They form a crucial component of the ‘sleep switch’ in the brain and promote arousal when activated. The histaminergic neurons are strongly innervated by ventrolateral preoptic area (VLPO) neurons expressing galanin, a neuropeptide associated with sleep promotion. While recent studies have confirmed the importance of VLPO projections to the TMN in initiating and maintaining sleep, the ability of galanin to modulate the activity of the wake-promoting histaminergic neurons of the TMN has largely been overlooked. Therefore, we aimed to determine the mechanisms by which galanin alters the electrical excitability of genetically identified histaminergic neurons. We hypothesized that galanin inhibits histaminergic neuron activity via direct post-synaptic activation of galanin 1 receptors (GalR1). Whole-cell patch-clamp electrophysiology was performed on hypothalamic brain slices from mice expressing tdTomato fluorescence in cells expressing histidine decarboxylase (HDC), the sole enzyme required for histamine synthesis (HDCCre::tdTomato mice). RNAscope ® in situ hybridization was used to explore Gal1R mRNA expression in HDC expressing neurons. Whole-cell current-clamp recordings in male mice revealed that galanin (100nM) inhibits the majority of HDC neurons. The galanin-induced inhibition was associated with a hyperpolarization of the membrane potential and a decrease in firing frequency. Consistent with our hypothesis, a selective galanin 2 receptor (Gal2R) agonist (M1145 - 200nM) had no effect on male HDC neuron activity. RNAscope ® studies in male mice revealed co-expression of Gal1R mRNA in a large proportion of HDC-expressing neurons. Interestingly, the galanin-induced inhibition of HDC neuron electrical excitability was less pronounced in female mice. Overall, our data point to an important role of post-synaptic Gal1Rs expressed on histaminergic neurons in mediating galanin’s inhibitory effects in the TMN. Our data also suggest that sex differences exist in histaminergic neuron responsiveness to galanin. These findings are consistent with the idea that some of the sleep promoting effects of VLPO neuron activation occur through galanin’s ability to inhibit the wake-active histaminergic neurons. Sleep Research Society (SRS), Canada First Research Excellence Fund (Sentinel North Partnered Research Chair in Sleep Pharmacometabolism), Fondation Institut Universitaire de Cardiologie et de Pneumologie de Quebec (FIUCPQ), Fonds de recherche de Quebec - Sante (FRQS). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".