Core Contributors

Patrick J. Drew

Professor of Engineering Science and Mechanics
Principal investigator

Techniques: Two-Photon Microscopy, Wide-field fluorescence and intrinsic signal imaging, Fiber photometry, Electrophysiology, Signal processing, Behavioral state monitoring

Md Shakhawat Hossain
PhD Student

Cholinergic and noradrenergic modulation of hemodynamics during sleep

Our aim is to understand the influence of norepinephrine (NE) and acetylcholine (ACh) on sleep-induced vasodilation and arterial pulsation. We hypothesize that ACh and NE modulation causes an alternating patterns of vasodilation and vasoconstriction during sleep that aid in driving cerebrospinal fluid (CSF) clearance. To understand this, we use fiber photometry and fluorescence biosensors to monitor cerebral blood volume and neuromodulators in mice cortex across sleep and wakefulness. Through optogenetic and chemogenetic adjustments of cortical NE and ACh levels, our aim is to discern the specific roles played by the cholinergic and norepinephrine systems in controlling brain vascular dynamics during sleep.

Techniques: Stereotaxic craniotomy and implantation, Intra-cortical and retro-orbital AAV injection, Fiber photometry, In-vivo recording, Sleep experiment, Optogenetic stimulation, Mouse behavior analysis, Analysis of fiber photometry recordings

Fatemeh Salehi
PhD Student
 

Dynamics of TAC1-expressing neurons across arousal states

Our aim is to understand which neuronal cell types cause vasodilation during sleep. For my experiments, I use wide-field calcium imaging to see how the activity of specific neurons within the cortex evolves in response to changes in cerebral blood flow (CBF) throughout sleep.

Techniques: Wide-field calcium imaging: IOS, cranial window and electrode implantation, AAV PHP.eB, Sleep behavioral analysis

Hyunseok Lee
Graduate Student

Interstitial fluid flow within a short time scale

We aim to identify the mode and magnitude of interstitial fluid flow at a short time scale. We will observe secreted fluorescence protein in extracellular space from transfected cells through the thinned-skull window by a resonant two-photon microscope. Acquired data will be analyzed by Fluorescence correlation spectroscopy, Paired correlation spectroscopy, and porosity change.

Techniques: Thinned Skull, Intracortical injection, IV injection,  2-photon imaging, Fluorescence correlation spectroscopy, paired correlation spectroscopy, extracellular space analysis, porosity analysis

Mike Wenke
MD-PhD Student

Noradrenergic neural control of cortical arterial dynamics during sleep-wake transitions

Our aim is to determine the relationship between cortical norepinephrine activity and blood vessel pulsations throughout natural sleep. We measure these using two photon imaging in head-fixed, skull-thinned mice while monitoring sleep state. Current work investigates how prolonged increases in norepinephrine biosensor fluorescence around penetrating arterioles are coupled with vasoconstriction and arousal from sleep, and how brief increases in NE throughout slow wave sleep correlate with arterial pulsations. We will next use optogenetic and chemogenetic manipulations to discern if norepinephrine release from locus coeruleus axonal projections are sufficient to drive vascular dynamics seen during natural sleep transitions and microarousals.

Techniques: Thinned Skull Cranial window, Intra-cortical and retro-orbital AAv injection, Mouse sleep and behavior tracking, two-photon imaging, Analysis of two-photon images, Confocal imaging