scholarly journals A genetically encoded tool for reconstituting synthetic modulatory neurotransmission and reconnect neural circuits in vivo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Josh D. Hawk ◽  
Elias M. Wisdom ◽  
Titas Sengupta ◽  
Zane D. Kashlan ◽  
Daniel A. Colón-Ramos

AbstractChemogenetic and optogenetic tools have transformed the field of neuroscience by facilitating the examination and manipulation of existing circuits. Yet, the field lacks tools that enable rational rewiring of circuits via the creation or modification of synaptic relationships. Here we report the development of HySyn, a system designed to reconnect neural circuits in vivo by reconstituting synthetic modulatory neurotransmission. We demonstrate that genetically targeted expression of the two HySyn components, a Hydra-derived neuropeptide and its receptor, creates de novo neuromodulatory transmission in a mammalian neuronal tissue culture model and functionally rewires a behavioral circuit in vivo in the nematode Caenorhabditis elegans. HySyn can interface with existing optogenetic, chemogenetic and pharmacological approaches to functionally probe synaptic transmission, dissect neuropeptide signaling, or achieve targeted modulation of specific neural circuits and behaviors.

Author(s):  
Josh D. Hawk ◽  
Daniel A. Colón-Ramos

Here we introduce HySyn, a system designed to rewire neural connectivity in vivo by reconstituting a functional heterologous synapse. We demonstrate that genetically targeted expression of the two HySyn components, a Hydra-derived neuropeptide and its receptor, creates de novo neuromodulatory transmission in a mammalian neuronal tissue culture model and rewires a behavioral circuit in vivo in the nematode Caenorhabditis elegans. HySyn can interface with existing optogenetic, chemogenetic and pharmacological approaches to functionally probe synaptic transmission, dissect neuropeptide signaling, or modulate specific neural circuits.


2007 ◽  
Vol 101 (3) ◽  
pp. 841-853 ◽  
Author(s):  
Thomas L. Shirley ◽  
J. Chris Lewers ◽  
Kiyoshi Egami ◽  
Alokes Majumdar ◽  
Mairead Kelly ◽  
...  

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Natasha Mehta ◽  
J Yasha Kresh ◽  
Steven P Kutalek ◽  
Peter A Lewin ◽  
Andrew R Kohut

Background: Ultrasound can interact with tissue through either thermal or non-thermal physical mechanisms. Radiation force has been shown to stimulate cardiac and neural tissue in vivo. Ultrasound might hold clinical potential as a noninvasive therapeutic tool via specific bioeffects on cardiomyocytes. This study aims to assess the effect of ultrasound on cardiomyocyte depolarization in a tissue culture model. Methods: Cardiomyocytes were isolated from neonatal rat ventricular tissue and plated directly on microelectrode arrays to record depolarization patterns. A custom 2.5 MHz unfocused ultrasound transducer was directed at the cardiomyocytes in a tissue culture model. A function generator, with an amplified signal +50 dB, delivered acoustic energy at variable settings of 0.1, 0.3, 0.5 and 1.0 Vpp, pulse durations of 2, 5 and 10 ms, and burst periods of 100, 250 and 300 ms. Five trials were conducted at each setting (36 total trials) with 30s of continuous ultrasound exposure followed by an off interval of 1 minute. Results: The R-R interval durations (ID) were measured throughout the recording period. Prior to ultrasound delivery, the IDs were highly irregular, ID range = 0.3-2.7 s. As ultrasound was delivered in an asynchronous manner, using 0.1 and 0.3 Vpp and PD = 2 and 5 ms, there was suppression/inhibition of cellular depolarization for the first 5-10 s. Then 10-15 s after the start of ultrasound delivery, the depolarization rate increased and demonstrated less R-R interval variability (ID=0.88-1.03 s, P value<0.05), even after the ultrasound exposure. Conclusion: Ultrasound can inhibit and modify the frequency of spontaneous electrical depolarizations of neonatal ventricular cardiomyocytes in a tissue culture model. Our observations could be due to conditioning via stretch and compression-mediated mechanosensitive pathways, by modifying intracellular calcium handling or altering cell signaling.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ru-Fang Siao ◽  
Chia-Hsuan Lin ◽  
Li-Hsuan Chen ◽  
Liang-Chun Wang

AbstractTeleost fish skin serves as the first line of defense against pathogens. The interaction between pathogen and host skin determines the infection outcome. However, the mechanism(s) that modulate infection remain largely unknown. A proper tissue culture model that is easier to handle but can quantitatively and qualitatively monitor infection progress may shed some lights. Here, we use striped catfish (Pangasius hypophthalmus) to establish an ex vivo skin explant tissue culture model to explore host pathogen interactions. The skin explant model resembles in vivo skin in tissue morphology, integrity, and immune functionality. Inoculation of aquatic pathogen Aeromonas hydrophila in this model induces epidermal exfoliation along with epithelial cell dissociation and inflammation. We conclude that this ex vivo skin explant model could serve as a teleost skin infection model for monitoring pathogenesis under various infection conditions. The model can also potentially be translated into a platform to study prevention and treatment of aquatic infection on the skin in aquaculture applications.


2009 ◽  
Vol 34 (5) ◽  
pp. 643-650 ◽  
Author(s):  
H. OMAE ◽  
C. ZHAO ◽  
Y.-L. SUN ◽  
M. E. ZOBITZ ◽  
S. L. MORAN ◽  
...  

The purpose of this study was to assess tendon metabolism and suture pull-out strength after simple tendon suture in a tissue culture model. One hundred and twelve flexor digitorum profundus tendons from 28 dogs were cultured for 7, 14, or 21 days with or without a static tensile load. In both groups increased levels of matrix metalloproteinase (MMP) mRNA was noted. Suture pull-out strength did not decrease during tissue culture. While the presence of a static load had no effect on the pull-out strength, it did affect MMP mRNA expression. This tissue culture model could be useful in studying the effect of factors on the tendon-suture interface.


2017 ◽  
Vol 38 (suppl_1) ◽  
Author(s):  
S. White ◽  
S. Satta ◽  
G.G. Hazell ◽  
J.E. Teasdale ◽  
A. Peachey ◽  
...  

2006 ◽  
Vol 3 (3) ◽  
pp. 339-348 ◽  
Author(s):  
Saburo Hidaka ◽  
Yoshizo Okamoto ◽  
Satoshi Uchiyama ◽  
Akira Nakatsuma ◽  
Ken Hashimoto ◽  
...  

Royal jelly (RJ) has been used worldwide for many years as medical products, health foods and cosmetics. Since RJ contains testosterone and has steroid hormone-type activities, we hypothesized that it may have beneficial effects on osteoporosis. We used both an ovariectomized rat model and a tissue culture model. Rats were divided into eight groups as follows: sham-operated (Sham), ovariectomized (OVX), OVX given 0.5% (w/w) raw RJ, OVX given 2.0% (w/w) RJ, OVX given 0.5% (w/w) protease-treated RJ (pRJ), OVX given 2.0% (w/w) pRJ, OVX given 17β-estradiol and OVX given its vehicle, respectively. The Ovariectomy decreased tibial bone mineral density (BMD) by 24%. Administration of 17β-estradiol to OVX rats recovered the tibial BMD decrease by 100%. Administration of 2.0% (w/w) RJ and 0.5–2.0% (w/w) pRJ to OVX rats recovered it by 85% or more. These results indicate that both RJ and pRJ are almost as effective as 17β-estradiol in preventing the development of bone loss induced by ovariectomy in rats. In tissue culture models, both RJ and pRJ increased calcium contents in femoral-diaphyseal and femoral-metaphyseal tissue cultures obtained from normal male rats. However, in a mouse marrow culture model, they neither inhibited the parathyroid hormone (PTH)-induced calcium loss nor affected the formation of osteoclast-like cells induced by PTH in mouse marrow culture system. Therefore, our results suggest that both RJ and pRJ may prevent osteoporosis by enhancing intestinal calcium absorption, but not by directly antagonizing the action of PTH.


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