scholarly journals Optogenetic stimulation of VIPergic SCN neurons induces photoperiodic changes in the mammalian circadian clock

2021 ◽  
Author(s):  
Michael C. Tackenberg ◽  
Jacob J. Hughey ◽  
Douglas G. McMahon
Keyword(s):  
Ex Vivo ◽  
Day Length ◽  
Optogenetic Stimulation ◽  
Period 2 ◽  
Free Running ◽  
Free Running Period ◽  
The Brain ◽  
Long Photoperiod ◽  
Stimulation Of

SummaryCircadian clocks play key roles in how organisms respond to and even anticipate seasonal change in day length, or photoperiod. In mammals, photoperiod is encoded by the central circadian pacemaker in the brain, the suprachiasmatic nucleus (SCN). The subpopulation of SCN neurons that secrete the neuropeptide VIP mediate the transmission of light information within the SCN neural network, suggesting a role for these neurons in circadian plasticity in response to light information that has yet to be directly tested. Here, we used in vivo optogenetic stimulation of VIPergic SCN neurons followed by ex vivo PERIOD 2::LUCIFERASE (PER2::LUC) bioluminescent imaging to test whether activation of this SCN neuron sub-population can induce SCN network changes that are hallmarks of photoperiodic encoding. We found that optogenetic stimulation designed to mimic a long photoperiod indeed altered subsequent SCN entrained phase, increased the phase dispersal of PER2 rhythms within the SCN network, and shortened SCN free-running period – similar to the effects of a true extension of photoperiod. Optogenetic stimulation also induced analogous changes on related aspects of locomotor behavior in vivo. Thus, selective activation of VIPergic SCN neurons induces photoperiodic network plasticity in the SCN which underpins photoperiodic entrainment of behavior.

scholarly journals Opposing Influence of Sensory and Motor Cortical Input on Striatal Circuitry and Choice Behavior

2018 ◽  
Author(s):  
Christian R. Lee ◽  
Alex J. Yonk ◽  
Joost Wiskerke ◽  
Kenneth G. Paradiso ◽  
James M. Tepper ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Dorsal Striatum ◽  
Behavioral Effect ◽  
Projection Neurons ◽  
Cortical Input ◽  
Optogenetic Stimulation ◽  
Main Input ◽  
Opposing Effects ◽  
Stimulation Of

SummaryThe striatum is the main input nucleus of the basal ganglia and is a key site of sensorimotor integration. While the striatum receives extensive excitatory afferents from the cerebral cortex, the influence of different cortical areas on striatal circuitry and behavior is unknown. Here we find that corticostriatal inputs from whisker-related primary somatosensory (S1) and motor (M1) cortex differentially innervate projection neurons and interneurons in the dorsal striatum, and exert opposing effects on sensory-guided behavior. Optogenetic stimulation of S1-corticostriatal afferents in ex vivo recordings produced larger postsynaptic potentials in striatal parvalbumin (PV)-expressing interneurons than D1- or D2-expressing spiny projection neurons (SPNs), an effect not observed for M1-corticostriatal afferents. Critically, in vivo optogenetic stimulation of S1-corticostriatal afferents produced task-specific behavioral inhibition, which was bidirectionally modulated by striatal PV interneurons. Optogenetic stimulation of M1 afferents produced the opposite behavioral effect. Thus, our results suggest opposing roles for sensory and motor cortex in behavioral choice via distinct influences on striatal circuitry.

scholarly journals Parylene photonics: a flexible, broadband optical waveguide platform with integrated micromirrors for biointerfaces

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Jay W. Reddy ◽  
Maya Lassiter ◽  
Maysamreza Chamanzar
Keyword(s):  
Optical Waveguides ◽  
Brain Activity ◽  
Low Loss ◽  
Parylene C ◽  
Optogenetic Stimulation ◽  
Patterned Illumination ◽  
The Brain ◽  
532 Nm ◽  
Stimulation Of

Abstract Targeted light delivery into biological tissue is needed in applications such as optogenetic stimulation of the brain and in vivo functional or structural imaging of tissue. These applications require very compact, soft, and flexible implants that minimize damage to the tissue. Here, we demonstrate a novel implantable photonic platform based on a high-density, flexible array of ultracompact (30 μm × 5 μm), low-loss (3.2 dB/cm at λ = 680 nm, 4.1 dB/cm at λ = 633 nm, 4.9 dB/cm at λ = 532 nm, 6.1 dB/cm at λ = 450 nm) optical waveguides composed of biocompatible polymers Parylene C and polydimethylsiloxane (PDMS). This photonic platform features unique embedded input/output micromirrors that redirect light from the waveguides perpendicularly to the surface of the array for localized, patterned illumination in tissue. This architecture enables the design of a fully flexible, compact integrated photonic system for applications such as in vivo chronic optogenetic stimulation of brain activity.

scholarly journals Wireless, battery-free, fully implantable multimodal and multisite pacemakers for applications in small animal models

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Philipp Gutruf ◽  
Rose T. Yin ◽  
K. Benjamin Lee ◽  
Jokubas Ausra ◽  
Jaclyn A. Brennan ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Small Animal ◽  
In Vivo Studies ◽  
Cardiovascular Research ◽  
Optogenetic Stimulation ◽  
Wide Range ◽  
Small Animal Models ◽  
Wireless Energy Harvesting ◽  
Stimulation Of

AbstractSmall animals support a wide range of pathological phenotypes and genotypes as versatile, affordable models for pathogenesis of cardiovascular diseases and for exploration of strategies in electrotherapy, gene therapy, and optogenetics. Pacing tools in such contexts are currently limited to tethered embodiments that constrain animal behaviors and experimental designs. Here, we introduce a highly miniaturized wireless energy-harvesting and digital communication electronics for thin, miniaturized pacing platforms weighing 110 mg with capabilities for subdermal implantation and tolerance to over 200,000 multiaxial cycles of strain without degradation in electrical or optical performance. Multimodal and multisite pacing in ex vivo and in vivo studies over many days demonstrate chronic stability and excellent biocompatibility. Optogenetic stimulation of cardiac cycles with in-animal control and induction of heart failure through chronic pacing serve as examples of modes of operation relevant to fundamental and applied cardiovascular research and biomedical technology.

scholarly journals In vivo optogenetic stimulation of the primate retina activates the visual cortex after long-term transduction

2021 ◽  
Author(s):  
Antoine Chaffiol ◽  
Matthieu Provansal ◽  
Corentin Joffrois ◽  
Kévin Blaize ◽  
Guillaume Labernede ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Information Transfer ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Spatiotemporal Resolution ◽  
Fluorescent Reporter ◽  
Optogenetic Stimulation ◽  
Stimulation Of

SummaryVarious therapeutic strategies for vision restoration have been developed, including retinal prostheses [1–4], stem cell transplantation [5–8] and optogenetic therapies [9,10,19,11–18]. In optogenetic therapy, the residual retinal neurons surviving the pathological degenerative process are rendered light-sensitive. Using this approach, we targeted the retinal ganglion cells (RGCs) through the in vivo expression of an ectopic light-sensitive ion channel, ChrimsonR [13] coupled to the fluorescent reporter tdTomato. The application of this strategy to blind patients [20] suffering from retinal dystrophies raises important concerns about the long-term functional expression of efficient signal transmission to higher brain centers (i.e. the visual cortex). We have previously shown that the transduced retina displays high spatiotemporal resolution ex vivo, compatible with the perception of highly dynamic visual scenes at light levels suitable for use in humans. Other studies have provided evidence of retinal activation in vivo [17]. Here, we demonstrate, in non-human primates, sustained functional efficacy ~20 months after delivery of an AAV2.7m8-ChrimsonR-tdTomato vector similar to that currently undergoing clinical evaluation. Our results reveal a persistence of expression in the perifovea, mediating information transfer to higher brain centers. Indeed, we recorded visually evoked potentials in the primary visual cortex of anesthetized animals in response to optogenetic retinal activation. We used an intravitreal injection of synaptic blockers to isolate the cortical component resulting from the in vivo optogenetic stimulation of primate RGCs. Our findings demonstrate the long-term functional efficacy of optogenetic retinal information transfer to the brain in vivo.

Implantable neural interfaces

2018 ◽  
Author(s):  
Stefano Vassanelli
Keyword(s):  
Brain Function ◽  
Large Scale ◽  
Ionic Channels ◽  
Patch Clamp Technique ◽  
Advantages And Disadvantages ◽  
Optogenetic Stimulation ◽  
Physical Interfaces ◽  
The Brain

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.

Striatal dopamine mediates hallucination-like perception in mice

Science ◽  
2021 ◽  
Vol 372 (6537) ◽  
pp. eabf4740
Author(s):  
K. Schmack ◽  
M. Bosc ◽  
T. Ott ◽  
J. F. Sturgill ◽  
A. Kepecs
Keyword(s):  
Psychotic Disorders ◽  
Neural Circuit ◽  
Dopamine Neurons ◽  
Striatal Dopamine ◽  
Model Organisms ◽  
High Confidence ◽  
Optogenetic Stimulation ◽  
The Brain ◽  
Central Symptom ◽  
Stimulation Of

Hallucinations, a central symptom of psychotic disorders, are attributed to excessive dopamine in the brain. However, the neural circuit mechanisms by which dopamine produces hallucinations remain elusive, largely because hallucinations have been challenging to study in model organisms. We developed a task to quantify hallucination-like perception in mice. Hallucination-like percepts, defined as high-confidence false detections, increased after hallucination-related manipulations in mice and correlated with self-reported hallucinations in humans. Hallucination-like percepts were preceded by elevated striatal dopamine levels, could be induced by optogenetic stimulation of mesostriatal dopamine neurons, and could be reversed by the antipsychotic drug haloperidol. These findings reveal a causal role for dopamine-dependent striatal circuits in hallucination-like perception and open new avenues to develop circuit-based treatments for psychotic disorders.

scholarly journals A method for single-neuron chronic recording from the retina in awake mice

Science ◽  
2018 ◽  
Vol 360 (6396) ◽  
pp. 1447-1451 ◽  
Author(s):  
Guosong Hong ◽  
Tian-Ming Fu ◽  
Mu Qiao ◽  
Robert D. Viveros ◽  
Xiao Yang ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Visual Information ◽  
Single Neuron ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Neural Circuitry ◽  
Retinal Ganglion ◽  
Chronic Recording ◽  
The Brain

The retina, which processes visual information and sends it to the brain, is an excellent model for studying neural circuitry. It has been probed extensively ex vivo but has been refractory to chronic in vivo electrophysiology. We report a nonsurgical method to achieve chronically stable in vivo recordings from single retinal ganglion cells (RGCs) in awake mice. We developed a noncoaxial intravitreal injection scheme in which injected mesh electronics unrolls inside the eye and conformally coats the highly curved retina without compromising normal eye functions. The method allows 16-channel recordings from multiple types of RGCs with stable responses to visual stimuli for at least 2 weeks, and reveals circadian rhythms in RGC responses over multiple day/night cycles.

Ex Vivo Brain Preparation to Analyze Vocal Pathways of Xenopus Frogs

2021 ◽  
Vol 2021 (9) ◽  
pp. pdb.prot106872
Author(s):  
Ayako Yamaguchi
Keyword(s):  
Neural Activity ◽  
Ex Vivo ◽  
Neural Circuitry ◽  
Neural Basis ◽  
Vocal Production ◽  
Basic Principles ◽  
Electrophysiological Recordings ◽  
The Brain

Understanding the neural basis of behavior is a challenging task for technical reasons. Most methods of recording neural activity require animals to be immobilized, but neural activity associated with most behavior cannot be recorded from an anesthetized, immobilized animal. Using amphibians, however, there has been some success in developing in vitro brain preparations that can be used for electrophysiological and anatomical studies. Here, we describe an ex vivo frog brain preparation from which fictive vocalizations (the neural activity that would have produced vocalizations had the brain been attached to the muscle) can be elicited repeatedly. When serotonin is applied to the isolated brains of male and female African clawed frogs, Xenopus laevis, laryngeal nerve activity that is a facsimile of those that underlie sex-specific vocalizations in vivo can be readily recorded. Recently, this preparation was successfully used in other species within the genus including Xenopus tropicalis and Xenopus victorianus. This preparation allows a variety of techniques to be applied including extracellular and intracellular electrophysiological recordings and calcium imaging during vocal production, surgical and pharmacological manipulation of neurons to evaluate their impact on motor output, and tract tracing of the neural circuitry. Thus, the preparation is a powerful tool with which to understand the basic principles that govern the production of coherent and robust motor programs in vertebrates.

scholarly journals Potential caveats of putative microglia-specific markers for assessment of age-related cerebrovascular neuroinflammation

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Pedram Honarpisheh ◽  
Juneyoung Lee ◽  
Anik Banerjee ◽  
Maria P. Blasco-Conesa ◽  
Parisa Honarpisheh ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Ex Vivo ◽  
Myeloid Cells ◽  
Amyloid Angiopathy ◽  
Future Studies ◽  
Age Related ◽  
In Vivo Animal Models ◽  
Intermediate Expression ◽  
The Brain

Abstract Background The ability to distinguish resident microglia from infiltrating myeloid cells by flow cytometry-based surface phenotyping is an important technique for examining age-related neuroinflammation. The most commonly used surface markers for the identification of microglia include CD45 (low-intermediate expression), CD11b, Tmem119, and P2RY12. Methods In this study, we examined changes in expression levels of these putative microglia markers in in vivo animal models of stroke, cerebral amyloid angiopathy (CAA), and aging as well as in an ex vivo LPS-induced inflammation model. Results We demonstrate that Tmem119 and P2RY12 expression is evident within both CD45int and CD45high myeloid populations in models of stroke, CAA, and aging. Interestingly, LPS stimulation of FACS-sorted adult microglia suggested that these brain-resident myeloid cells can upregulate CD45 and downregulate Tmem119 and P2RY12, making them indistinguishable from peripherally derived myeloid populations. Importantly, our findings show that these changes in the molecular signatures of microglia can occur without a contribution from the other brain-resident or peripherally sourced immune cells. Conclusion We recommend future studies approach microglia identification by flow cytometry with caution, particularly in the absence of the use of a combination of markers validated for the specific neuroinflammation model of interest. The subpopulation of resident microglia residing within the “infiltrating myeloid” population, albeit small, may be functionally important in maintaining immune vigilance in the brain thus should not be overlooked in neuroimmunological studies.

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