Locus Coeruleus Stimulation Recruits a Broad Cortical Neuronal Network and Increases Cortical Perfusion
Bibliographic record
Abstract
The locus coeruleus (LC), the main source of brain noradrenalin (NA), modulates cortical activity, cerebral blood flow (CBF), glucose metabolism, and blood-brain barrier permeability. However, the role of the LC-NA system in the regulation of cortical CBF has remained elusive. This rat study shows that similar proportions (∼20%) of cortical pyramidal cells and GABA interneurons are contacted by LC-NA afferents on their cell soma or proximal dendrites. LC stimulation induced ipsilateral activation (c-Fos upregulation) of pyramidal cells and of a larger proportion (>36%) of interneurons that colocalize parvalbumin, somatostatin, or nitric oxide synthase compared with pyramidal cells expressing cyclooxygenase-2 (22%, p < 0.05) or vasoactive intestinal polypeptide-containing interneurons (16%, p < 0.01). Concurrently, LC stimulation elicited larger ipsilateral compared with contralateral increases in cortical CBF (52 vs 31%, p < 0.01). These CBF responses were almost abolished (-70%, p < 0.001) by cortical NA denervation with DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride] and were significantly reduced by α- and β-adrenoceptor antagonists (-40%, p < 0.001 and -30%, p < 0.05, respectively). Blockade of glutamatergic or GABAergic neurotransmission with NMDA or GABA(A) receptor antagonists potently reduced the LC-induced hyperemic response (-56%, p < 0.001 or -47%, p < 0.05). Moreover, inhibition of astroglial metabolism (-35%, p < 0.01), vasoactive epoxyeicosatrienoic acids (EETs; -60%, p < 0.001) synthesis, large-conductance, calcium-operated (BK, -52%, p < 0.05), and inward-rectifier (Kir, -40%, p < 0.05) K+ channels primarily impaired the hyperemic response. The data demonstrate that LC stimulation recruits a broad network of cortical excitatory and inhibitory neurons resulting in increased cortical activity and that K+ fluxes and EET signaling mediate a large part of the hemodynamic response.
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 | 0.001 | 0.007 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".