scholarly journals A novel theoretical framework for simultaneous measurement of excitatory and inhibitory conductances

2021 ◽  
Vol 17 (12) ◽  
pp. e1009725
Author(s):  
Daniel Müller-Komorowska ◽  
Ana Parabucki ◽  
Gal Elyasaf ◽  
Yonatan Katz ◽  
Heinz Beck ◽  
...  

The firing of neurons throughout the brain is determined by the precise relations between excitatory and inhibitory inputs, and disruption of their balance underlies many psychiatric diseases. Whether or not these inputs covary over time or between repeated stimuli remains unclear due to the lack of experimental methods for measuring both inputs simultaneously. We developed a new analytical framework for instantaneous and simultaneous measurements of both the excitatory and inhibitory neuronal inputs during a single trial under current clamp recording. This can be achieved by injecting a current composed of two high frequency sinusoidal components followed by analytical extraction of the conductances. We demonstrate the ability of this method to measure both inputs in a single trial under realistic recording constraints and from morphologically realistic CA1 pyramidal model cells. Future experimental implementation of our new method will facilitate the understanding of fundamental questions about the health and disease of the nervous system.

2021 ◽  
Author(s):  
Daniel Muller-Komorowska ◽  
Ana Parabucki ◽  
Gal Elyasaf ◽  
Yonatan Katz ◽  
Heinz Beck ◽  
...  

Firing of neurons throughout the brain is determined by the precise relations between excitatory and inhibitory inputs and disruption of their balance underlies many psychiatric diseases. Whether or not these inputs covary over time or between repeated stimuli remains unclear due to the lack of experimental methods for measuring both inputs simultaneously. We developed a new analytical framework for instantaneous and simultaneous measurements of both the excitatory and inhibitory neuronal inputs during a single trial under current clamp recording. This can be achieved by injecting a current composed of two high frequency sinusoidal components followed by analytical extraction of the conductances. We demonstrate the ability of this method to measure both inputs in a single trial under realistic recording constraints and from morphologically realistic CA1 pyramidal model cells. Experimental implementation of our new method will facilitate the understanding of fundamental questions about the health and disease of the nervous system.


2019 ◽  
Author(s):  
Ilan Lampl

AbstractNeuronal activity is determined by the interplay between excitatory and inhibitory inputs of individual cells. Whether or not these inputs covary over time or between repeated stimuli remains unclear due to the lack of experimental methods for measuring both inputs at the same time. Current methods for conductance measurement are based on repeatedly stimulating neurons while holding their membrane potential at different levels so to reveal either excitation or inhibition, which can only provide the averaged relationship between the two. Here we develop a new framework for simultaneously measuring both the excitatory and inhibitory inputs of single cells in a single trial under current clamp. This method is based on theoretical analysis of passive circuits and can be practically achieved by injecting a high frequency sinusoidal current and then analysing the data using an optimization algorithm. We use simulations to demonstrate the ability of this approach to reveal the excitatory and inhibitory inputs of point neurons, in which we mimic adapting sensory inputs as well as an asynchronous balanced state.


2017 ◽  
Vol 57 (5) ◽  
pp. 801
Author(s):  
P. I. Hynd

Several sheep-husbandry practices such as mulesing, castration, ear-tagging and tail-docking are currently performed with no, or little, anaesthesia or analgesia. The potential for using electrotherapies to provide analgesia during and after these operations is examined in this review. The most common electrotherapy is transcutaneous electrical nerve stimulation (TENS). TENS is the application of an electrical current from electrodes placed on the skin. Analysis of a large number of trials in humans and in animal models indicates that TENS provides effective relief from acute and chronic pain, including pain associated with surgery. There is strong evidence now that TENS analgesia operates at the levels of the periphery, the spinal cord and in the brain. The mechanisms involve the autonomic nervous system, the opioid pathways and neurotransmitters involved in descending inhibitory pathways from the brain. Centrally operating pathways mean the current does not have to be applied near the injured site and there is evidence of sustained pain relief lasting hours, days or even weeks post-treatment, particularly after very high-frequency, randomly variable current applications. Treatment of sheep during painful operations with such a current has the potential to provide immediate and possibly sustained pain relief. Combining such a treatment with electro-immobilisation of the animal would be advantageous for sheep-husbandry operations, but there is considerable evidence that high-intensity currents producing tetanic contractions are aversive and probably painful for sheep. Investigations of the application and efficacy of electrotherapies for painful sheep operations should be undertaken.


2020 ◽  
Vol 44 (3) ◽  
pp. 241-249
Author(s):  
Yoshiaki Omura

While a visiting Professor at the University of Paris, VI (formerly Sorvonne) more than 40 years ago, the Author became very good friends with Dr. Paul Nogier who periodically gave seminars and workshops in Paris. After the author diagnosed his cervical problem & offered him simple help, Dr. Nogier asked the Author to present lectures and demonstrations on the effects of ear stimulation, namely the effects of acupuncture & electrical stimulation of the ear lobules. It is only now, in 2019 that we have discovered 2–5 minute high frequency stimulation of the ear lobule inhibits cancer activity for 1– 4 hours post stimulation. Although the procedure is extremely simple. First take optimal dose of Vitamin D3, which has the most essential 10 unique beneficial factors required for every human cell activity. Next, apply high frequency stimulation to ear lobule while the worst ear lobule is held by all fingers with vibrator directly touching the surface of the worst ear lobule, preferably after patient repeatedly takes optimal dose of Vitamin D3. When the worst ear lobule is held between thumb & index fingers and applying mechanical stimulation of 250 ~ 500 mechanical vibration/second for 2 ~ 5 minutes using an electrical vibrator, there is rapid disappearance of cancer activity in both the brain and rest of the body for short time duration 1 ~ 4 hours. The effect often increases by additional pressure by holding fingers. As of May 2019, the Author found that many people from various regions of the world developed early stages of multiple cancers. For evaluation of this study, U. S. patented Bi-Digital O-Ring Test (BDORT) was used which was developed by the Author while doing his Graduate experimental physics research at Colombia University. BDORT was found to be most essential for determining the beneficial effects as well as harmful effects of any substance or treatment. Using BDORT, Author was the first to recognize severe increasing mid-backache was an early sign of pancreatic cancer of President of New York State Board of Medicine after top pain specialists failed to detect the cause after 3 years of effort, while the BDORT showed early stages of cancer whereas conventional X-Ray of the pancreas did not show any cancer image until 2 months after Author detected with BDORT. For example, the optimal dose of the banana is usually about 2.0 - 2.5 millimeters cross section of the banana. A whole banana is more than 50 ~ 100 times the optimal dose. Any substance eaten in more than 25 times of its optimal dose becomes highly toxic and creates DNA mutations which can cause multiple malignancies in the presence of strong electro-magnetic field. With standard medication given by doctor, patients often become sick and they are unable to reduce body weight, unless medication is reduced or completely stopped. When the amount of zinc is very high, DNA often becomes unstable and multiple cancers can grow rapidly in the presence of strong electromagnetic field. Large amount of Vitamin C from regular orange or orange juice inhibit the most important Vitamin D3 effects. At least 3 kinds of low Vitamin C oranges will not inhibit Vitamin D3. Since B12 particularly methyl cobalamin which is a red small tablet is known to improve brain circulation very significantly we examined its effect within 20 seconds of oral intake we found the following very significant changes. Acetylcholine in both sides of the brain often increases over 4,500 ng. Longevity gene Sirtuin 1 level increases significantly for short time of few hours. Thymosin α1 and Thymosinβ4 both increase to over 1500 ng from 20 ng or less.


Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 142
Author(s):  
Mariella Cuomo ◽  
Luca Borrelli ◽  
Rosa Della Monica ◽  
Lorena Coretti ◽  
Giulia De Riso ◽  
...  

The bidirectional microbiota–gut–brain axis has raised increasing interest over the past years in the context of health and disease, but there is a lack of information on molecular mechanisms underlying this connection. We hypothesized that change in microbiota composition may affect brain epigenetics leading to long-lasting effects on specific brain gene regulation. To test this hypothesis, we used Zebrafish (Danio Rerio) as a model system. As previously shown, treatment with high doses of probiotics can modulate behavior in Zebrafish, causing significant changes in the expression of some brain-relevant genes, such as BDNF and Tph1A. Using an ultra-deep targeted analysis, we investigated the methylation state of the BDNF and Tph1A promoter region in the brain and gut of probiotic-treated and untreated Zebrafishes. Thanks to the high resolution power of our analysis, we evaluated cell-to-cell methylation differences. At this resolution level, we found slight DNA methylation changes in probiotic-treated samples, likely related to a subgroup of brain and gut cells, and that specific DNA methylation signatures significantly correlated with specific behavioral scores.


2021 ◽  
Vol 46 (1) ◽  
pp. 77-87
Author(s):  
Arnaud Tauffenberger ◽  
Pierre J. Magistretti

AbstractCellular homeostasis plays a critical role in how an organism will develop and age. Disruption of this fragile equilibrium is often associated with health degradation and ultimately, death. Reactive oxygen species (ROS) have been closely associated with health decline and neurological disorders, such as Alzheimer’s disease or Parkinson’s disease. ROS were first identified as by-products of the cellular activity, mainly mitochondrial respiration, and their high reactivity is linked to a disruption of macromolecules such as proteins, lipids and DNA. More recent research suggests more complex function of ROS, reaching far beyond the cellular dysfunction. ROS are active actors in most of the signaling cascades involved in cell development, proliferation and survival, constituting important second messengers. In the brain, their impact on neurons and astrocytes has been associated with synaptic plasticity and neuron survival. This review provides an overview of ROS function in cell signaling in the context of aging and degeneration in the brain and guarding the fragile balance between health and disease.


2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Petra Mohácsik ◽  
Anikó Zeöld ◽  
Antonio C. Bianco ◽  
Balázs Gereben

Thyroid hormone plays a crucial role in the development and function of the nervous system. In order to bind to its nuclear receptor and regulate gene transcription thyroxine needs to be activated in the brain. This activation occurs via conversion of thyroxine to T3, which is catalyzed by the type 2 iodothyronine deiodinase (D2) in glial cells, in astrocytes, and tanycytes in the mediobasal hypothalamus. We discuss how thyroid hormone affects glial cell function followed by an overview on the fine-tuned regulation of T3 generation by D2 in different glial subtypes. Recent evidence on the direct paracrine impact of glial D2 on neuronal gene expression underlines the importance of glial-neuronal interaction in thyroid hormone regulation as a major regulatory pathway in the brain in health and disease.


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