Optogenetically induced cellular habituation in non-neuronal cells.
Ontology highlight
ABSTRACT:
SUBMITTER: Bonzanni M
PROVIDER: S-EPMC6968872 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Transient gamma-band (40-80 Hz) spatiotemporal patterns are hypothesized to play important roles in cortical function. Here we report the direct observation of gamma oscillations as spatiotemporal waves induced by targeted optogenetic stimulation, recorded by intracortical multichannel extracellular techniques in macaque monkeys during their awake resting states. Microelectrode arrays integrating an optical fiber at their center were chronically implanted in primary motor (M1) and ventral premotor (PMv) cortices of two subjects. Targeted brain tissue was transduced with the red-shifted opsin C1V1(T/T). Constant (1-s square pulses) and ramp stimulation induced narrowband gamma oscillations during awake resting states. Recordings across 95 microelectrodes (4 × 4-mm array) enabled us to track the transient gamma spatiotemporal patterns manifested, e.g., as concentric expanding and spiral waves. Gamma oscillations were induced well beyond the light stimulation volume, via network interactions at distal electrode sites, depending on optical power. Despite stimulation-related modulation in spiking rates, neuronal spiking remained highly asynchronous during induced gamma oscillations. In one subject we examined stimulation effects during preparation and execution of a motor task and observed that movement execution largely attenuated optically induced gamma oscillations. Our findings demonstrate that, beyond previously reported induced gamma activity under periodic drive, a prolonged constant stimulus above a certain threshold may carry primate motor cortex network dynamics into gamma oscillations, likely via a Hopf bifurcation. More broadly, the experimental capability in combining microelectrode array recordings and optogenetic stimulation provides an important approach for probing spatiotemporal dynamics in primate cortical networks during various physiological and behavioral conditions.
| S-EPMC4461886 | biostudies-literature
Project description:Glomeruli are the functional units of olfactory information processing but little remains known about their individual unit function. This is due to their widespread activation by odor stimuli. We expressed channelrhodopsin-2 in a single olfactory sensory neuron type, and used laser stimulation and simultaneous in vivo calcium imaging to study the responses of a single glomerulus to optogenetic stimulation. Calcium signals in the neuropil of this glomerulus were representative of the sensory input and nearly identical if evoked by intensity-matched odor and laser stimuli. However, significantly fewer glomerular layer interneurons and olfactory bulb output neurons (mitral cells) responded to optogenetic versus odor stimuli, resulting in a small and spatially compact optogenetic glomerular unit response. Temporal features of laser stimuli were represented with high fidelity in the neuropil of the glomerulus and the mitral cells, but not in interneurons. Increases in laser stimulus intensity were encoded by larger signal amplitudes in all compartments of the glomerulus, and by the recruitment of additional interneurons and mitral cells. No spatial expansion of the glomerular unit response was observed in response to stronger input stimuli. Our data are among the first descriptions of input-output transformations in a selectively activated olfactory glomerulus.
| S-EPMC6175855 | biostudies-other
Project description:Protein kinases are involved in the regulation of many cellular processes including cell differentiation, survival, migration, axon guidance and neuronal plasticity. A growing set of optogenetic tools, termed opto-kinases, allows activation and inhibition of different protein kinases with light. The optogenetic regulation enables fast, reversible and non-invasive manipulation of protein kinase activities, complementing traditional methods, such as treatment with growth factors, protein kinase inhibitors or chemical dimerizers. In this review, we summarize the properties of the existing optogenetic tools for controlling tyrosine kinases and serine-threonine kinases. We discuss how the opto-kinases can be applied for studies of spatial and temporal aspects of protein kinase signaling in cells and organisms. We compare approaches for chemical and optogenetic regulation of protein kinase activity and present guidelines for selection of opto-kinases and equipment to control them with light. We also describe strategies to engineer novel opto-kinases on the basis of various photoreceptors.
| S-EPMC5882534 | biostudies-literature
Project description:BackgroundLeucine-rich repeat kinase 2 (LRRK2) plays a critical role in the pathogenesis of Parkinson's disease (PD). Aging is the most critical risk factor for the progression of PD. The correlation between aging and cellular senescence has been established. Cellular senescence is correlated with the dysregulation of the proteolytic pathway and mitochondrial dysfunction, which are also associated with the aggregation of α-synuclein (α-syn).MethodsHuman dopaminergic neuron-like cells (differentiated SH-SY5Y cells) were treated with rotenone in the presence or absence of the LRRK2 kinase inhibitor GSK2578215A (GSK-KI) for 48 h. The markers of cellular senescence, including p53, p21Waf1/Cip1 (p21), β-galactosidase (β-gal), Rb phosphorylation, senescence-associated (SA) β-gal activity, and lysosomal activity, were examined. The dSH cells and rat primary cortical neurons were treated with α-syn fibrils 30 min before treatment with rotenone in the presence or absence of GSK-KI for 48 h. Mice were intraperitoneally injected with rotenone and MLi-2 (LRRK2 kinase inhibitor) once every two days for two weeks.ResultsRotenone upregulated LRRK2 phosphorylation and β-gal levels through the activation of the p53-p21 signaling axis and downregulated Rb phosphorylation. Additionally, rotenone upregulated SA β-gal activity, reactive oxygen species levels, and LRRK2 phosphorylation and inhibited lysosome activity. Rotenone-induced LRRK2 upregulation impaired the clearance of α-syn fibrils. Treatment with LRRK2 inhibitor mitigated rotenone-induced cellular senescence and α-syn accumulation.ConclusionsRotenone-induced upregulation of LRRK2 kinase activity promoted cellular senescence, which enhanced α-syn accumulation. However, the administration of an LRRK2 kinase inhibitor rejuvenated rotenone-induced cellular senescence.
| S-EPMC8282384 | biostudies-literature
Project description:Disturbances in neuronal differentiation and function are an underlying factor of many brain disorders. Zinc homeostasis and signaling are important mediators for a normal brain development and function, given that zinc deficiency was shown to result in cognitive and emotional deficits in animal models that might be associated with neurodevelopmental disorders. One underlying mechanism of the observed detrimental effects of zinc deficiency on the brain might be impaired proliferation and differentiation of stem cells participating in neurogenesis. Thus, to examine the molecular mechanisms regulating zinc metabolism and signaling in differentiating neurons, using a protocol for motor neuron differentiation, we characterized the expression of zinc homeostasis genes during neurogenesis using human induced pluripotent stem cells (hiPSCs) and evaluated the influence of altered zinc levels on the expression of zinc homeostasis genes, cell survival, cell fate, and neuronal function. Our results show that zinc transporters are highly regulated genes during neuronal differentiation and that low zinc levels are associated with decreased cell survival, altered neuronal differentiation, and, in particular, synaptic function. We conclude that zinc deficiency in a critical time window during brain development might influence brain function by modulating neuronal differentiation.
| S-EPMC4876239 | biostudies-literature
Project description:Deployment of covert attention to a spatial location can cause large decreases in low-frequency correlated variability among neurons in macaque area V4 whose receptive-fields lie at the attended location. It has been estimated that this reduction accounts for a substantial fraction of the attention-mediated improvement in sensory processing. These estimates depend on assumptions about how population signals are decoded and the conclusion that correlated variability impairs perception, is purely hypothetical. Here we test this proposal directly by optogenetically inducing low-frequency fluctuations, to see if this interferes with performance in an attention-demanding task. We find that low-frequency optical stimulation of neurons in V4 elevates correlations among pairs of neurons and impairs the animal's ability to make fine sensory discriminations. Stimulation at higher frequencies does not impair performance, despite comparable modulation of neuronal responses. These results support the hypothesis that attention-dependent reductions in correlated variability contribute to improved perception of attended stimuli.
| S-EPMC6391072 | biostudies-literature
Project description:Huntington's disease (HD) is an inherited, relentlessly progressive neurodegenerative disease with an invariably fatal outcome. HD is inherited in an autosomal dominant fashion, and is characterized pathologically by the loss of cortical and striatal neurons, and clinically by involuntary choreiform movements accompanied by progressive cognitive impairment and emotional lability. The disorder is caused by an expanded cystosine adenine guanine (CAG) tri-nucleotide repeat encoding polyglutamine (polyQ) in the first exon of the Huntingtin gene. There is a correlation between the number of CAG repeats and disease onset, such that in patients with CAG repeat lengths of 36 to 60, disease symptoms typically manifest after 35 years of age, whereas CAG repeat lengths >60 yield the more severe juvenile form of the disease. Even though mutant huntingtin is expressed throughout the brain, it is characterized by the selective degeneration of medium spiny neurons of the caudate and putamen, which heralds more widespread neuronal degeneration with disease progression. The mechanisms of cell dysfunction and death in HD have been the subjects of a number of studies, which have led to therapeutic strategies largely based on the amelioration of mutant huntingtin-related metabolic impairment and cellular toxicity. Each of these approaches has aimed to delay or stop the preferential degeneration of medium spiny neurons early in the disease course. Yet, in later stages of the disease, after cell death has become prominent, cell replacement therapy (whether by direct cell transplantation or by the mobilization of endogenous progenitors) may comprise a stronger potential avenue for therapy. In this review, we will consider recent progress in the transplantation of fetal striatal cells to the HD brain, as well as emerging alternative sources for human striatal progenitor cells. We will then consider the potential application of gene therapy toward the induction of striatal neurogenesis and neuronal recruitment, with an eye toward its potential therapeutic use in HD.
| S-EPMC3250300 | biostudies-literature
Project description:Epileptic seizure is a paroxysmal and self-limited phenomenon characterized by abnormal hypersynchrony of a large population of neurons. However, our current understanding of seizure dynamics is still limited. Here we propose a novel in vivo model of seizure-like afterdischarges using optogenetics, and report on investigation of directional network dynamics during seizure along the septo-temporal (ST) axis of hippocampus. Repetitive pulse photostimulation was applied to the rodent hippocampus, in which channelrhodopsin-2 (ChR2) was expressed, under simultaneous recording of local field potentials (LFPs). Seizure-like afterdischarges were successfully induced after the stimulation in both W-TChR2V4 transgenic (ChR2V-TG) rats and in wild type rats transfected with adeno-associated virus (AAV) vectors carrying ChR2. Pulse frequency at 10 and 20 Hz, and a 0.05 duty ratio were optimal for afterdischarge induction. Immunohistochemical c-Fos staining after a single induced afterdischarge confirmed neuronal activation of the entire hippocampus. LFPs were recorded during seizure-like afterdischarges with a multi-contact array electrode inserted along the ST axis of hippocampus. Granger causality analysis of the LFPs showed a bidirectional but asymmetric increase in signal flow along the ST direction. State space presentation of the causality and coherence revealed three discrete states of the seizure-like afterdischarge phenomenon: 1) resting state; 2) afterdischarge initiation with moderate coherence and dominant septal-to-temporal causality; and 3) afterdischarge termination with increased coherence and dominant temporal-to-septal causality. A novel in vivo model of seizure-like afterdischarge was developed using optogenetics, which was advantageous in its reproducibility and artifact-free electrophysiological observations. Our results provide additional evidence for the potential role of hippocampal septo-temporal interactions in seizure dynamics in vivo. Bidirectional networks work hierarchically along the ST hippocampus in the genesis and termination of epileptic seizures.
| S-EPMC3622611 | biostudies-literature
Project description:Habituation is the process that enables salience filtering, precipitating perceptual changes that alter the value of environmental stimuli. To discern the neuronal circuits underlying habituation to brief inconsequential stimuli, we developed a novel olfactory habituation paradigm, identifying two distinct phases of the response that engage distinct neuronal circuits. Responsiveness to the continuous odor stimulus is maintained initially, a phase we term habituation latency and requires Rutabaga Adenylyl-Cyclase-depended neurotransmission from GABAergic Antennal Lobe Interneurons and activation of excitatory Projection Neurons (PNs) and the Mushroom Bodies. In contrast, habituation depends on the inhibitory PNs of the middle Antenno-Cerebral Track, requires inner Antenno-Cerebral Track PN activation and defines a temporally distinct phase. Collectively, our data support the involvement of Lateral Horn excitatory and inhibitory stimulation in habituation. These results provide essential cellular substrates for future analyses of the molecular mechanisms that govern the duration and transition between these distinct temporal habituation phases. Editorial note:This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
| S-EPMC6303106 | biostudies-literature
Project description:This study tested the hypothesis that autistic traits influence the neuronal habituation that underlies the processing of others' pain. Based on their autism-spectrum quotient (AQ), two groups of participants were classified according to their autistic traits: High-AQ and Low-AQ groups. Their event-related potentials in response to trains of three identical audio recordings, exhibiting either painful or neutral feelings of others, were compared during three experimental tasks. (1) In a Pain Judgment Task, participants were instructed to focus on pain-related cues in the presented audio recordings. (2) In a Gender Judgment Task, participants were instructed to focus on non-pain-related cues in the presented audio recordings. (3) In a Passive Listening Task, participants were instructed to passively listen. In the High-AQ group, an altered empathic pattern of habituation, indexed by frontal-central P2 responses of the second repeated painful audio recordings, was found during the Passive Listening Task. Nevertheless, both High-AQ and Low-AQ groups exhibited similar patterns of habituation to hearing others' voices, both neutral and painful, in the Pain Judgment and Gender Judgment Tasks. These results suggest altered empathic neuronal habituation in the passive processing of others' vocal pain by individuals with autistic traits.
| S-EPMC7490706 | biostudies-literature