scholarly journals Intrinsic Cell-type Selectivity and Inter-neuronal Connectivity Alteration by Transcranial Focused Ultrasound

2019 ◽  
Author(s):  
Kai Yu ◽  
Xiaodan Niu ◽  
Esther Krook-Magnuson ◽  
Bin He
Keyword(s):  
Focused Ultrasound ◽  
Inhibitory Neurons ◽  
Synaptic Connectivity ◽  
Fast Spiking ◽  
First Time ◽  
Transcranial Focused Ultrasound ◽  
Specific Neuron ◽  
Ultrasound Pulse

ABSTRACTTranscranial focused ultrasound (tFUS) is a promising neuromodulation technique, but its mechanisms remain unclear. We investigate the effect of tFUS stimulation on different neuron types and synaptic connectivity in in vivo anesthetized rodent brains. Single units were separated into regular-spiking and fast-spiking units based on their extracellular spike shapes, further validated in transgenic optogenetic mice models of light-excitable excitatory and inhibitory neurons. For the first time, we show that excitatory neurons are significantly less responsive to low ultrasound pulse repetition frequencies (UPRFs), whereas the spike rates of inhibitory neurons do not change significantly across all UPRF levels. Our results suggest that we can preferentially target specific neuron types noninvasively by altering the tFUS UPRF. We also report in vivo observation of long-term synaptic connectivity changes induced by noninvasive tFUS in rats. This finding suggests tFUS can be used to encode temporally dependent stimulation paradigms into neural circuits and non-invasively elicit long-term changes in synaptic connectivity.

scholarly journals Intrinsic functional neuron-type selectivity of transcranial focused ultrasound neuromodulation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kai Yu ◽  
Xiaodan Niu ◽  
Esther Krook-Magnuson ◽  
Bin He
Keyword(s):  
Focused Ultrasound ◽  
Pulse Repetition Frequency ◽  
Inhibitory Neurons ◽  
Neuron Populations ◽  
Electrophysiological Recordings ◽  
Fast Spiking ◽  
Functional Neuron ◽  
Transcranial Focused Ultrasound ◽  
Ultrasound Pulse

AbstractTranscranial focused ultrasound (tFUS) is a promising neuromodulation technique, but its mechanisms remain unclear. We hypothesize that if tFUS parameters exhibit distinct modulation effects in different neuron populations, then the mechanism can be understood through identifying unique features in these neuron populations. In this work, we investigate the effect of tFUS stimulation on different functional neuron types in in vivo anesthetized rodent brains. Single neuron recordings were separated into regular-spiking and fast-spiking units based on their extracellular spike shapes acquired through intracranial electrophysiological recordings, and further validated in transgenic optogenetic mice models of light-excitable excitatory and inhibitory neurons. We show that excitatory and inhibitory neurons are intrinsically different in response to ultrasound pulse repetition frequency (PRF). The results suggest that we can preferentially target specific neuron types noninvasively by tuning the tFUS PRF. Chemically deafened rats and genetically deafened mice were further tested for validating the directly local neural effects induced by tFUS without potential auditory confounds.

scholarly journals Dynamics of intravital concentration of amino acid metabolites in human brain in post-traumatic period

2019 ◽  
Vol 484 (2) ◽  
pp. 238-242
Author(s):  
N. A. Semenova ◽  
P. E. Menshchikov ◽  
A. V. Manzhurtsev ◽  
M. V. Ublinskiy ◽  
T. A. Akhadov ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Amino Acid ◽  
Human Brain ◽  
Leading Role ◽  
Acid Metabolites ◽  
Post Traumatic ◽  
First Time

Intracellular concentrations of N acetyaspartate (NAA), aspartate (Asp) and glutamate (Glu) were determined for the first time in human brain in vivo, and the effect of severe traumatic brain injury on NAA synthesis in acute and late post-traumatic period was investigated. In MRI‑negative frontal lobes one day after injury Asp and Glu levels were found to decrease by 45 and 35%, respectively, while NAA level decreased by only 16%. A negative correlation between NAA concentration and the ratio of Asp/Glu concentrations was found. In the long-term period, Glu level returned to normal, Asp level remained below normal by 60%, NAA level was reduced by 65% relative to normal, and Asp/Glu ratio significantly decreased. The obtained results revealed leading role of the neuronal aspartate-malate shuttle in violation of NAA synthesis.

Auditory Thalamocortical Transmission Is Reliable and Temporally Precise

2005 ◽  
Vol 94 (3) ◽  
pp. 2019-2030 ◽  
Author(s):  
Heather J. Rose ◽  
Raju Metherate
Keyword(s):  
Primary Auditory Cortex ◽  
Inhibitory Neurons ◽  
Latency Variability ◽  
Medial Geniculate ◽  
Low Jitter ◽  
Fast Spiking ◽  
Whole Cell Recordings ◽  
Minimal Stimulation ◽  
Juvenile Mouse

We have used the auditory thalamocortical slice to characterize thalamocortical transmission in primary auditory cortex (ACx) of the juvenile mouse. “Minimal” stimulation was used to activate medial geniculate neurons during whole cell recordings from regular-spiking (RS cells; mostly pyramidal) and fast-spiking (FS, putative inhibitory) neurons in ACx layers 3 and 4. Excitatory postsynaptic potentials (EPSPs) were considered monosynaptic (thalamocortical) if they met three criteria: low onset latency variability (jitter), little change in latency with increased stimulus intensity, and little change in latency during a high-frequency tetanus. Thalamocortical EPSPs were reliable (probability of postsynaptic responses to stimulation was ∼1.0) as well as temporally precise (low jitter). Both RS and FS neurons received thalamocortical input, but EPSPs in FS cells had faster rise times, shorter latencies to peak amplitude, and shorter durations than EPSPs in RS cells. Thalamocortical EPSPs depressed during repetitive stimulation at rates (2–300 Hz) consistent with thalamic spike rates in vivo, but at stimulation rates ≥40 Hz, EPSPs also summed to activate N-methyl-d-aspartate receptors and trigger long-lasting polysynaptic activity. We conclude that thalamic inputs to excitatory and inhibitory neurons in ACx activate reliable and temporally precise monosynaptic EPSPs that in vivo may contribute to the precise timing of acoustic-evoked responses.

scholarly journals Latent Antigen Vaccination in a Model Gammaherpesvirus Infection

2001 ◽  
Vol 75 (17) ◽  
pp. 8283-8288 ◽  
Author(s):  
Edward J. Usherwood ◽  
Kimberley A. Ward ◽  
Marcia A. Blackman ◽  
James P. Stewart ◽  
David L. Woodland
Keyword(s):  
Latent Infection ◽  
Model Systems ◽  
Murine Gammaherpesvirus ◽  
Latently Infected ◽  
Associated Proteins ◽  
Infected Cells ◽  
The Impact ◽  
First Time

ABSTRACT Vaccines that can reduce the load of latent gammaherpesvirus infections are eagerly sought. One attractive strategy is vaccination against latency-associated proteins, which may increase the efficiency with which T cells recognize and eliminate latently infected cells. However, due to the lack of tractable animal model systems, the effect of latent-antigen vaccination on gammaherpesvirus latency is not known. Here we use the murine gammaherpesvirus model to investigate the impact of vaccination with the latency-associated M2 antigen. As expected, vaccination had no effect on the acute lung infection. However, there was a significant reduction in the load of latently infected cells in the initial stages of the latent infection, when M2 is expressed. These data show for the first time that latent-antigen vaccination can reduce the level of latency in vivo and suggest that vaccination strategies involving other latent antigens may ultimately be successfully used to reduce the long-term latent infection.

scholarly journals Nanoagents for improving focused ultrasound thermal delivery to tumors with imaging feedback

2018 ◽  
Author(s):  
Paul Dayton
Keyword(s):  
Spatial Distribution ◽  
Focused Ultrasound ◽  
Near Field ◽  
Tumor Model ◽  
In Vivo Studies ◽  
Hifu Treatment ◽  
Hifu Ablation ◽  
Delivery Efficiency

We have developed a unique metastable nanodroplet formulation which data suggests 1) will improve thermal delivery efficiency of intensity focused ultrasound (HIFU) ablation in vivo, and 2) will improve the spatial distribution of thermal delivery at the acoustic focus, without near-field attenuation or heating. In this project, we will test and optimize our approach by quantifying nanodroplet dose and improvements in thermal delivery efficiency in vivo using MRgFUS; assessing long term circulation in vivo; and by performing MRgFUS in vivo studies in rodent tumor model to validate nanodropletenhanced HIFU treatment of tumors, compared to sham controls. Finally, we will perform histology to assess tissue for collateral bioeffects.

scholarly journals In vivo monitoring of tissue regeneration using a ratiometric lysosomal AIE probe

2020 ◽  
Vol 11 (12) ◽  
pp. 3152-3163 ◽  
Author(s):  
Xiujuan Shi ◽  
Neng Yan ◽  
Guangle Niu ◽  
Simon H. P. Sung ◽  
Zhiyang Liu ◽  
...  
Keyword(s):  
Tissue Regeneration ◽  
Caudal Fin ◽  
Fin Regeneration ◽  
Lysosomal Ph ◽  
In Vivo Monitoring ◽  
Ratiometric Probe ◽  
First Time

An AIE-active ratiometric probe for the first time achieved the long-term quantification of lysosomal pH during the medaka larva's caudal fin regeneration.

scholarly journals Transcranial focused ultrasound pulsation suppresses pentylenetetrazol induced epilepsy in vivo

2020 ◽  
Vol 13 (1) ◽  
pp. 35-46 ◽  
Author(s):  
Sin-Guang Chen ◽  
Chih-Hung Tsai ◽  
Chia-Jung Lin ◽  
Cheng-Chia Lee ◽  
Hsiang-Yu Yu ◽  
...  
Keyword(s):  
Focused Ultrasound ◽  
Transcranial Focused Ultrasound

scholarly journals The horse as a model for translational orthopedic research: examples of studies on the regeneration of cartilage and bone conducted in Costa Rica

2019 ◽  
Vol 37 (3) ◽  
pp. 9-10
Author(s):  
Rafael Vindas Bolaños ◽  
Jos Malda ◽  
René Van Weeren ◽  
Janny De Grauw
Keyword(s):  
Bone Defects ◽  
Chondral Defects ◽  
Fixation Techniques ◽  
Equine Studies ◽  
First Time ◽  
Adhesive Capacity ◽  
Stimulation Of ◽  
Long Term Studies

The paper provides results published or to be published of long-term in vivo equine studies to evaluate techniques of possible regenerative matrices of cartilage and bone, by means of cell-free implants or stimulation of the bone marrow. From the fixation techniques analyzed, it can be concluded that the best alternatives are the pressure technique for subchondral defects and a novel hydrogel with self-adhesive capacity for chondral defects. The equine coxal tuberosity was used for the first time as a model for regeneration studies of bone defects, analyzing scaffolds based on tricalcium phosphate, polymers and nanoparticles, by means of 3-D printing. Osteoconductivity, osteoinductivity, and the importance of microporosity were documented.Given that decellularized materials do not always give significant desired results in the regeneration of cartilage, it is important to conduct long-term studies. The technique of nanofracture and a novel self-adhesive hydrogel in the knee of the equine showed promising preliminary results in the regeneration of cartilage.The knee and the coxal tuberosity of the horse represent models of studying cartilage and bone regeneration in a true translational sense as a source of highly valuable information for clinical studies, for both horses and humans.

scholarly journals Establishment and Characterization of Human Germline Stem Cell Line with Unlimited Proliferation Potentials and no Tumor Formation

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Jingmei Hou ◽  
Minghui Niu ◽  
Linhong Liu ◽  
Zijue Zhu ◽  
Xiaobo Wang ◽  
...  
Keyword(s):  
Cell Line ◽  
T Antigen ◽  
Tumor Formation ◽  
Germline Stem Cell ◽  
Sv40 Large T Antigen ◽  
Western Blots ◽  
Transplantation Assay ◽  
First Time

Abstract Spermatogonial stem cells (SSCs) have significant applications in both reproductive and regenerative medicine. However, primary human SSCs are very rare and a human SSC line has not yet been available. In this study, we have for the first time reported a stable human SSC line by stably expressing human SV40 large T antigen. RT-PCR, immunocytochemistry and Western blots revealed that this cell line was positive for a number of human spermatogonial and SSC hallmarks, including VASA, DAZL, MAGEA4, GFRA1, RET, UCHL1, GPR125, PLZF and THY1, suggesting that these cells are human SSCs phenotypically. Proliferation analysis showed that the cell line could be expanded with significant increases of cells for 1.5 years and high levels of PCNA, UCHL1 and SV40 were maintained for long-term culture. Transplantation assay indicated that human SSC line was able to colonize and proliferate in vivo in the recipient mice. Neither Y chromosome microdeletions of numerous genes nor tumor formation was observed in human SSC line although there was abnormal karyotype in this cell line. Collectively, we have established a human SSC line with unlimited proliferation potentials and no tumorgenesis, which could provide an abundant source of human SSCs for their mechanistic studies and translational medicine.

Synaptic Connectivity in Cultured Hypothalamic Neuronal Networks

1997 ◽  
Vol 77 (6) ◽  
pp. 3218-3225 ◽  
Author(s):  
Thomas H. Müller ◽  
D. Swandulla ◽  
H. U. Zeilhofer
Keyword(s):  
Neuronal Networks ◽  
Network Formation ◽  
Inhibitory Neurons ◽  
Synaptic Connectivity ◽  
Synaptic Connections ◽  
Cellular Mechanisms ◽  
Patch Clamp Technique ◽  
Novel Approach

Müller, Thomas H., D. Swandulla, and H. U. Zeilhofer. Synaptic connectivity in cultured hypothalamic neuronal networks. J. Neurophysiol. 77: 3218–3225, 1997. We have developed a novel approach to analyze the synaptic connectivity of spontaneously active networks of hypothalamic neurons in culture. Synaptic connections were identified by recording simultaneously from pairs of neurons using the whole cell configuration of the patch-clamp technique and testing for evoked postsynaptic current responses to electrical stimulation of one of the neurons. Excitatory and inhibitory responses were distinguished on the basis of their voltage and time dependence. The distribution of latencies between presynaptic stimulation and postsynaptic response showed multiple peaks at regular intervals, suggesting that responses via both monosynaptic and polysynaptic paths were recorded. The probability that an excitatory event is transmitted to another excitatory neuron and results in an above-threshold stimulation was found to be only one in three to four. This low value indicates that in addition to evoked synaptic responses other sources of excitatory drive must contribute to the spontaneous activity observed in these networks. The various types of synaptic connections (excitatory and inhibitory, monosynaptic, and polysynaptic) were counted, and the observations analyzed using a probabilistic model of the network structure. This analysis provides estimates for the ratio of inhibitory to excitatory neurons in the network (1:1.5) and for the ratio of postsynaptic cells receiving input from a single GABAergic or glutamatergic neuron (3:1). The total number of inhibitory synaptic connections was twice that of excitatory connections. Cell pairs mutually connected by an excitatory and an inhibitory synapse occurred significantly more often than predicted by a random process. These results suggests that the formation of neuronal networks in vitro is controlled by cellular mechanisms that favor inhibitory connections in general and specifically enhance the formation of reciprocal connections between pairs of excitatory and inhibitory neurons. These mechanisms may contribute to network formation and function in vivo.

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