Modulatory Effects of Noradrenergic and Serotonergic Signaling Pathway on Neurovascular Coupling

Renden, Robert; Institóris, Ádám; Sharma, Kushal; Tran, Cam Ha T.

doi:10.2139/ssrn.4456210

Cited by 1 publication

(6 citation statements)

References 67 publications

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“…Until now, most studies of NVC in the whisker barrel cortex have used a forced stimulation protocol. In anesthetized mice, this may be electrical (Wang, Lou et al 2006, Lind, Brazhe et al 2013, Mishra, Reynolds et al 2016 or in awake stimulations, an air puff or mechanical whisker deflection (Ding, O'Donnell et al 2013, Stobart, Ferrari et al 2018, Tran, Peringod et al 2018, Sharma, Gordon et al 2020, Renden, Institoris et al 2024. In some previous studies of evoked NVC, the duration of rhythmical deflections of the whiskers has, at times, been excessively long (Lind, Brazhe et al 2013, Institoris, Vandal et al 2022).…”

Section: Discussionmentioning

confidence: 99%

“…To inves gate this, we inhibited the release of NA from locus coeruleus by trea ng the mice with DSP-4 48 hours before the imaging session. This neurotoxin is known to abolish the NAreleasing neuronal projec ons from locus coeruleus to the barrel cortex (Iannitelli, Kelberman et al 2023) and lower the general cor cal NA levels (Slezak, Kandler et al 2019, Renden, Ins toris et al 2024.…”

Section: During Voli Onal Whisking Early Astrocy C Ca2+ Ac Vity Depen...mentioning

confidence: 99%

“…To test this, we targeted noradrenergic neurons in the LC using DSP-4. This neurotoxin eliminates NA-releasing neuronal projections from the LC, including to the barrel cortex (Iannitelli, Kelberman et al 2023) and lowers cortical NA globally (Slezak, Kandler et al 2019, Renden, Institoris et al 2024. To confirm its effect on astrocyte Ca2+ activity, we measured the long-duration surges (> 5s long) with the dynamic ROI detection analysis (Supplemental Figure S3).…”

Section: During Self-initiated Whisking Early Astrocytic Ca2+ Activit...mentioning

confidence: 99%

“…The ming of the increased astrocy c Ca2+ ac vity during locomo on excluded that it could explain this mismatch. We used DSP-4, a neurotoxin that transiently eliminates the noradrenergic projec ons from locus coeruleus (Slezak, Kandler et al 2019, Renden, Ins toris et al 2024, to inves gate the NA contribu on to NVC. The effect of this treatment on the three different whisking-related NVC responses was dissimilar.…”

Section: Introduc Onmentioning

confidence: 99%

“…The size and location of the early astrocytic Ca2+ activity correlated with the size and location of neuronal excitation across all behavioral categories. We used DSP-4, a neurotoxin that eliminates the noradrenergic projections from locus coeruleus (Slezak, Kandler et al 2019, Renden, Institoris et al 2024 to investigate the NA contribution to NVC. We found that NVC was differentially affected in each of our three whisking-related behavioral categories.…”

Section: Introductionmentioning

confidence: 99%

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Localised Astrocyte Ca2+ Activity Regulates Neurovascular Coupling Responses to Active Sensing

Stelzner,

Krogsgaard,

Kulkoviene

et al. 2024

Preprint

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The process of neurovascular coupling (NVC) is the regulation of sufficient and targeted blood flow during energy-consuming cerebral processes. Astrocyte participation in NVC has long been debated. The lack of clear answers is likely based on the diversity of astrocyte intracellular Ca2+ activities and the multitude of ways astrocytes may regulate cerebral blood flow. We focused our investigation on NVC responses to sensory input actively reached for by freely behaving mice. To do so, we studied the cellular and vascular activity in the sensory whisker barrel cortex of awake head-fixed mice and aligned this activity to the volitional whisking events. We compared the NVC initiated by the whisking event in the resting mouse to the whisking evoked by the experimenter and the whisking prior to locomotion. We did this comparison because astrocyte signaling is known to be sensitive to brain state transitions. In the NVC response to all three, we found that both neuronal and astrocytic activity corresponded to vascular activity. When we repeated this investigation after depletion of NA release from locus coeruleus projections, we identified that the three NVC responses did not equally depend on NA delivery or astrocytic activity. Though we found the expected effect on astrocytic Ca2+ surges, the whisking-dependent astrocytic Ca2+ activity was only moderately reduced by the reduced NA levels in the resting mouse and only in cells near the vessels. On the vascular side, we found that the dilation of the 1st order capillary to volitional whisking was much reduced. This suggests a disturbance in the precision regulation of the cerebral blood flow that may limit the appropriate delivery of blood to the region of activated neurons. Finally, this disturbance might partially account for the extended period of exploratory whisking prior to the initiation of locomotion that we saw in the NA-depleted mice. Our study reveals an astrocytic contribution to NVC in the natural shifts in the attention directed toward the sensory input received during volitional whisking.

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Section: Discussionmentioning

confidence: 99%

Section: During Voli Onal Whisking Early Astrocy C Ca2+ Ac Vity Depen...mentioning

confidence: 99%

Section: During Self-initiated Whisking Early Astrocytic Ca2+ Activit...mentioning

confidence: 99%

Section: Introduc Onmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Localised Astrocyte Ca2+ Activity Regulates Neurovascular Coupling Responses to Active Sensing

Stelzner,

Krogsgaard,

Kulkoviene

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Modulatory Effects of Noradrenergic and Serotonergic Signaling Pathway on Neurovascular Coupling

Cited by 1 publication

References 67 publications

Localised Astrocyte Ca2+ Activity Regulates Neurovascular Coupling Responses to Active Sensing

Localised Astrocyte Ca2+ Activity Regulates Neurovascular Coupling Responses to Active Sensing

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