Leveraging Optogenetic-Based Neurovascular Circuit Characterization for Repair

Ivanova, Elena; Yee, Christopher; Sagdullaev, Botir T.

doi:10.1007/s13311-015-0419-x

Cited by 5 publications

(3 citation statements)

References 55 publications

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“…Wild-type mice on a C57BL/6 background were used for experiments assessing the effects of exogenous ACh and 5-HT on neuronal activity. To study the effects of endogenous ACh release on neural activity, mice that heterozygously express blue-light sensitive channelrhodopsin in ChAT-containing cholinergic projections neurons (ChAT-ChR2-YFP BAC) on a C57BL/6 background were used (Zhao et al, 2011 ; Ivanova et al, 2016 ), permitting blue light stimulation to trigger the release of ACh from presynaptic terminals. Additional experiments were performed in mice heterozygous for ChATcre (ChAT-IRES-Cre, Rossi et al, 2011 ; Chen et al, 2016 ) and for Ai32 (RCL-ChR2(H134R)/EYFP, Madisen et al, 2012 ; O’Neill et al, 2017 ), a second mouse line that led to expression of blue-light sensitive channelrhodopsin in ChAT-containing cholinergic projections neurons.…”

Section: Methodsmentioning

confidence: 99%

Opposing Cholinergic and Serotonergic Modulation of Layer 6 in Prefrontal Cortex

Sparks

Tian

Sargin

et al. 2018

Front. Neural Circuits

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Prefrontal cortex is a hub for attention processing and receives abundant innervation from cholinergic and serotonergic afferents. A growing body of evidence suggests that acetylcholine (ACh) and serotonin (5-HT) have opposing influences on tasks requiring attention, but the underlying neurophysiology of their opposition is unclear. One candidate target population is medial prefrontal layer 6 pyramidal neurons, which provide feedback modulation of the thalamus, as well as feed-forward excitation of cortical interneurons. Here, we assess the response of these neurons to ACh and 5-HT using whole cell recordings in acute brain slices from mouse cortex. With application of exogenous agonists, we show that individual layer 6 pyramidal neurons are bidirectionally-modulated, with ACh and 5-HT exerting opposite effects on excitability across a number of concentrations. Next, we tested the responses of layer 6 pyramidal neurons to optogenetic release of endogenous ACh or 5-HT. These experiments were performed in brain slices from transgenic mice expressing channelrhodopsin in either ChAT-expressing cholinergic neurons or Pet1-expressing serotonergic neurons. Light-evoked endogenous neuromodulation recapitulated the effects of exogenous neurotransmitters, showing opposing modulation of layer 6 pyramidal neurons by ACh and 5-HT. Lastly, the addition of 5-HT to either endogenous or exogenous ACh significantly suppressed the excitation of pyramidal neurons in prefrontal layer 6. Taken together, this work suggests that the major corticothalamic layer of prefrontal cortex is a substrate for opposing modulatory influences on neuronal activity that could have implications for regulation of attention.

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Section: Methodsmentioning

confidence: 99%

Opposing Cholinergic and Serotonergic Modulation of Layer 6 in Prefrontal Cortex

Sparks

Tian

Sargin

et al. 2018

Front. Neural Circuits

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“…Completion of the superficial plexus outgrowth coincides with the disappearance of Stage2 waves, suggesting a possible causal link between these events. However, specifically manipulating cholinergic activity mostly affects the deep plexus formation during the second postnatal week (Weiner et al, 2019), indicating that cholinergic signaling per se does not mediate the earliest angiogenesis phase, despite being involved in blood flow control in the adult retina (Ivanova et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Novel transient cell clusters provide a possible link between early neural activity and angiogenesis in the neonatal mouse retina

Montigny

Thorne

Bhattacharya

et al. 2022

Preprint

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Developing neurons become spontaneously active while growing blood vessels begin to irrigate their surroundings. However, surprising little is known about early interactions between neural activity and angiogenesis. In the neonatal mouse retina, spontaneous waves of impulses sweep across the ganglion cell layer (GCL), just underneath the growing superficial vascular plexus. We discovered clusters of transient auto-fluorescent cells in the GCL, forming an annulus that co-localizes with the frontline of the growing plexus. Blood vessel density is highest within cluster areas, suggesting their involvement in angiogenesis. Once the clusters and blood vessels reach the retinal periphery by the end of the first postnatal week, the clusters disappear, eliminated by microglial phagocytosis. Electrical imaging suggests that they have their own electrophysiological signature. Blocking Pannexin1 (PANX1) hemi-channels with probenecid blocks the waves and the fluorescent clusters disappear following prolonged exposure to the drug. Spontaneous waves initiation points follow a developmental center-to-periphery progression similar to the cluster cells. We suggest that these transient cells are specialized, hyperactive neurons residing in the GCL. They generate spontaneous activity hotspots, thereby triggering waves through purinergic paracrine signaling via PANX1 hemi-channels. The strong activity generated around these hotspots triggers angiogenesis, attracting new blood vessels that provide local oxygen supply. Signaling through PANX-1 attracts microglia that establish contact with these cells, eventually leading to their elimination by phagocytosis. These cluster cells may provide the first evidence that specialized transient neuronal populations guide angiogenesis in the developing CNS through neural activity.

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“…An attractive early target for these new tools is the retina, which possesses the advantages of accessibility and immune privilege. In the final chapter in this section, Dr. Botir Sagdullaev and colleagues [7] show how optogenetic-based approaches can be used to restore light sensitivity after the loss of photoreceptors, demonstrating how close to clinical application these new tools have come.…”

mentioning

confidence: 99%