scholarly journals Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors

Science ◽  
2018 ◽  
Vol 360 (6396) ◽  
pp. eaat4422 ◽  
Author(s):  
Tommaso Patriarchi ◽  
Jounhong Ryan Cho ◽  
Katharina Merten ◽  
Mark W. Howe ◽  
Aaron Marley ◽  
...  

Neuromodulatory systems exert profound influences on brain function. Understanding how these systems modify the operating mode of target circuits requires spatiotemporally precise measurement of neuromodulator release. We developed dLight1, an intensity-based genetically encoded dopamine indicator, to enable optical recording of dopamine dynamics with high spatiotemporal resolution in behaving mice. We demonstrated the utility of dLight1 by imaging dopamine dynamics simultaneously with pharmacological manipulation, electrophysiological or optogenetic stimulation, and calcium imaging of local neuronal activity. dLight1 enabled chronic tracking of learning-induced changes in millisecond dopamine transients in mouse striatum. Further, we used dLight1 to image spatially distinct, functionally heterogeneous dopamine transients relevant to learning and motor control in mouse cortex. We also validated our sensor design platform for developing norepinephrine, serotonin, melatonin, and opioid neuropeptide indicators.

Author(s):  
Stefano Vassanelli

Establishing direct communication with the brain through physical interfaces is a fundamental strategy to investigate brain function. Starting with the patch-clamp technique in the seventies, neuroscience has moved from detailed characterization of ionic channels to the analysis of single neurons and, more recently, microcircuits in brain neuronal networks. Development of new biohybrid probes with electrodes for recording and stimulating neurons in the living animal is a natural consequence of this trend. The recent introduction of optogenetic stimulation and advanced high-resolution large-scale electrical recording approaches demonstrates this need. Brain implants for real-time neurophysiology are also opening new avenues for neuroprosthetics to restore brain function after injury or in neurological disorders. This chapter provides an overview on existing and emergent neurophysiology technologies with particular focus on those intended to interface neuronal microcircuits in vivo. Chemical, electrical, and optogenetic-based interfaces are presented, with an analysis of advantages and disadvantages of the different technical approaches.


2019 ◽  
Vol 10 (2) ◽  
pp. 789 ◽  
Author(s):  
Cuong Nguyen ◽  
Hansini Upadhyay ◽  
Michael Murphy ◽  
Gabriel Borja ◽  
Emily J. Rozsahegyi ◽  
...  

2021 ◽  
Author(s):  
Sebastian Junge ◽  
Felix Schmieder ◽  
Phillip Sasse ◽  
Jurgen Czarske ◽  
Maria Leilani Torres-Mapa ◽  
...  

2019 ◽  
Vol 5 (10) ◽  
pp. eaav9786 ◽  
Author(s):  
Ahsan Habib ◽  
Xiangchao Zhu ◽  
Uryan I. Can ◽  
Maverick L. McLanahan ◽  
Pinar Zorlutuna ◽  
...  

Harnessing the unprecedented spatiotemporal resolution capability of light to detect electrophysiological signals has been the goal of scientists for nearly 50 years. Yet, progress toward that goal remains elusive due to lack of electro-optic translators that can efficiently convert electrical activity to high photon count optical signals. Here, we introduce an ultrasensitive and extremely bright nanoscale electric-field probe overcoming the low photon count limitations of existing optical field reporters. Our electro-plasmonic nanoantennas with drastically enhanced cross sections (~104 nm2 compared to typical values of ~10−2 nm2 for voltage-sensitive fluorescence dyes and ~1 nm2 for quantum dots) offer reliable detection of local electric-field dynamics with remarkably high sensitivities and signal–to–shot noise ratios (~60 to 220) from diffraction-limited spots. In our electro-optics experiments, we demonstrate high-temporal resolution electric-field measurements at kilohertz frequencies and achieved label-free optical recording of network-level electrogenic activity of cardiomyocyte cells with low-intensity light (11 mW/mm2).


2008 ◽  
Vol 99 (6) ◽  
pp. 3136-3143 ◽  
Author(s):  
S. R. Lockery ◽  
K. J. Lawton ◽  
J. C. Doll ◽  
S. Faumont ◽  
S. M. Coulthard ◽  
...  

With a nervous system of only 302 neurons, the free-living nematode Caenorhabditis elegans is a powerful experimental organism for neurobiology. However, the laboratory substrate commonly used in C. elegans research, a planar agarose surface, fails to reflect the complexity of this organism's natural environment, complicates stimulus delivery, and is incompatible with high-resolution optophysiology experiments. Here we present a new class of microfluidic devices for C. elegans neurobiology and behavior: agarose-free, micron-scale chambers and channels that allow the animals to crawl as they would on agarose. One such device mimics a moist soil matrix and facilitates rapid delivery of fluid-borne stimuli. A second device consists of sinusoidal channels that can be used to regulate the waveform and trajectory of crawling worms. Both devices are thin and transparent, rendering them compatible with high-resolution microscope objectives for neuronal imaging and optical recording. Together, the new devices are likely to accelerate studies of the neuronal basis of behavior in C. elegans.


2018 ◽  
Vol 119 (2) ◽  
pp. 441-458 ◽  
Author(s):  
Minseok Kang ◽  
Young-Beom Lee ◽  
Bakul Gohel ◽  
Kwangsun Yoo ◽  
Peter Lee ◽  
...  

Complex spatiotemporal changes of slow spontaneous activity occur in the form of propagating waves in the cortex, leading to the transient formation of a specific activation topography, followed by a transition in the topography. The topographies resemble the stimulation-induced activation patterns and the underlying structural projections, suggesting that they contain motifs of task-related activation. However, little is known about how propagation-mediated transitions between topographies are structured in terms of functional connectivity. Therefore, we investigated whether specific topographies or regions are associated with transitions involving long-range connections and hub modulation. We hypothesized that the activity level of the default mode network (DMN) at a given topography would affect the pattern of upcoming transitions, since high activity levels of the DMN are a distinct feature of the brain at rest. Using mesoscale voltage-sensitive dye imaging in the cortex of lightly anesthetized mice, we revealed that momentary levels of DMN activity are associated with distinct patterns of activity propagation and functional connectivity. High levels of DMN activity led to activity propagation across secondary and association cortices, increasing the centrality of a main hub region, whereas low-level activity led to global, diffuse, yet efficient changes in functional connectivity. Furthermore, low levels of activity resulted in increased long-range connectivity between frontal and posterior regions of the cortex. Our results indicate that DMN activity is associated with functional connectivity and wave propagation patterns, raising the possibility that the DMN may be involved in the modulation of long-range information processing associated with upcoming transitions. NEW & NOTEWORTHY Using voltage-sensitive dye imaging with high spatiotemporal resolution, we have revealed that increased DMN activity is associated with activity propagation to secondary/association cortices, whereas decreased activity is associated with stronger long-range frontal-posterior connections in the mouse cortex. Hub metric and global functional connectivity parameters were accompanied by activity level changes. These results indicate that the DMN may aid in modulating the structure of transitions.


2019 ◽  
Author(s):  
Daniel A. Lee ◽  
Grigorios Oikonomou ◽  
Tasha Cammidge ◽  
Young Hong ◽  
David A. Prober

ABSTRACTAlthough several sleep-regulating neurons have been identified, little is known about how they interact with each other for sleep/wake control. We previously identified neuropeptide VF (NPVF) and the hypothalamic neurons that produce it as a sleep-promoting system (Lee et al., 2017). Here we use zebrafish to describe a neural circuit in which neuropeptide VF (npvf)-expressing neurons control sleep via the serotonergic raphe nuclei (RN), a hindbrain structure that promotes sleep in both diurnal zebrafish and nocturnal mice. Using genetic labeling and calcium imaging, we show that npvf-expressing neurons innervate and activate serotonergic RN neurons. We additionally demonstrate that optogenetic stimulation of npvf-expressing neurons induces sleep in a manner that requires NPVF and is abolished when the RN are ablated or lack serotonin. Finally, genetic epistasis demonstrates that NPVF acts upstream of serotonin in the RN to maintain normal sleep levels. These findings reveal a novel hypothalamic-hindbrain circuit for sleep/wake control.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ryan S Phillips ◽  
Ian Rosner ◽  
Aryn H Gittis ◽  
Jonathan E Rubin

As a rodent basal ganglia (BG) output nucleus, the substantia nigra pars reticulata (SNr) is well positioned to impact behavior. SNr neurons receive GABAergic inputs from the striatum (direct pathway) and globus pallidus (GPe, indirect pathway). Dominant theories of action selection rely on these pathways’ inhibitory actions. Yet, experimental results on SNr responses to these inputs are limited and include excitatory effects. Our study combines experimental and computational work to characterize, explain, and make predictions about these pathways. We observe diverse SNr responses to stimulation of SNr-projecting striatal and GPe neurons, including biphasic and excitatory effects, which our modeling shows can be explained by intracellular chloride processing. Our work predicts that ongoing GPe activity could tune the SNr operating mode, including its responses in decision-making scenarios, and GPe output may modulate synchrony and low-frequency oscillations of SNr neurons, which we confirm using optogenetic stimulation of GPe terminals within the SNr.


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