Biology subjects

Bergel, A.

Publications and source records attributed to Bergel, A..

3 recordsLinked to original sources

bioRxiv2026

Focal drug uncaging for the precise control of endogenous nicotinic receptors in behaving mice

Nicotinic acetylcholine receptors shape diverse brain functions, including reward, aversion, and pain, but dissecting their roles in vivo requires drug delivery with spatiotemporal precision that conventional pharmacology cannot provide. Here we establish in vivo photopharmacology of endogenous nicotinic receptors: two complementary, highly-potent agonists, administered systemically in an inactive caged form, are photoreleased locally in target brain circuits of behaving wild-type mice. Despite irreversible photochemistry, photoactivation can be repeated over many trials on a minute timescale, for hours following a single injection. Local uncaging evokes circuit-specific dopamine release, drives place preference from the ventral tegmental area and aversion from the interpeduncular nucleus, and, in pain circuits, reveals a pronociceptive effect masked when the same agonists are given systemically. By controlling where and when nicotinic signaling acts, this approach exposes circuit-specific drug effects invisible to conventional pharmacology, and outlines a general strategy for on-demand control of endogenous receptors in vivo.

neuroscience↗

bioRxiv2021

Volumetric ultrasound localization microscopy of the whole brain microvasculature

Technologies to visualize whole organs across scales in vivo are essential for our understanding of biology in health and disease. To date, only post-mortem techniques such as perfused computed tomography scanning or optical microscopy of cleared tissues achieve cellular resolution across entire organs and imaging methods with equal performance in living mammalian organs have yet to be developed. Recently, 2D ultrasound localization microscopy has successfully mapped the fine-scale vasculature of various organs down to a 10 m precision. However, reprojection issues and out-of-plane motion prevent complex blood flow quantification and fast volumetric imaging of whole organs. Here, we demonstrate for the first time in vivo volumetric ultrasound localization microscopy mapping of the rodent brain vasculature. We developed a complete methodological pipeline that includes specific surgery, a dedicated 3D ultrasound acquisition sequence, localization and tracking algorithms, motion correction and realignment, as well as the post-processing quantification of cerebral blood flow. We illustrate the power of this approach, by mapping the whole rat brain vasculature at a resolution of 12 m, revealing mesoscopic to macroscopic vascular architectures and cerebral blood flows ranging from 1 to 100 mm/s. Our results pave the way to the investigation of in vivo vascular processes across the mammalian brain in health and disease, in a wide range of contexts and models.

bioengineering↗

bioRxiv2020

Online modulation of brain hemodynamics despite stereotyped running

Theta and gamma rhythms coordinate large cell assemblies during locomotion. Their spread across temporal and spatial scales makes them challenging to observe. Additionally, the metabolic cost of these oscillations and their contribution to neuroimaging signals remains elusive. To finely characterize neurovascular interactions in running rats, we monitored brain hemodynamics with functional ultrasound and hippocampal local field potentials in running rats. Theta rhythm and running speed were strongly coupled to brain hemodynamics in multiple structures, with delays ranging from 0.8 seconds to 1.8 seconds. Surprisingly, hemodynamics was also strongly modulated across trials within the same recording session: cortical hemodynamics sharply decreased after 5-10 runs, while hippocampal hemodynamics strongly and linearly potentiated, particularly in the CA regions. This effect occurred while running speed and theta activity remained constant, and was accompanied by increased power in hippocampal high-frequency oscillations (100-150 Hz). Our findings reveal distinct vascular subnetworks modulated across fast and slow timescales and suggest strong adaptation processes despite stereotyped behavior.

neuroscience↗