scholarly journals Effect of Neuritic Cables on Conductance Estimates for Remote Electrical Synapses

2003 ◽  
Vol 89 (4) ◽  
pp. 2215-2224 ◽  
Author(s):  
Astrid A. Prinz ◽  
Peter Fromherz

The conductance of electrical synapses is usually estimated from voltage recordings at the neuronal somata under the assumption that each cell is isopotential. This approach neglects effects of intervening neurites. For a cell pair with unbranched neurites and an electrical synapse at their ends, we used cable theory to derive an analytical expression that relates the synaptic conductance to voltage recordings at the cell bodies and to the neurite properties. The equation implies that the conventional method significantly underestimates the actual synapse conductance if the neurite length is comparable to the electrotonic length constant and if the synaptic conductance is similar to the serial neurite conductance. For an experimental test, we cultured pairs of snail neurons on protein patterns, resulting in a geometry that matched the theoretical model. Using the isopotential theory, we estimated the synapse conductances and found them to be rather weak. To obtain the cable properties, we recorded spatiotemporal maps of signal propagation in the neurites using a voltage-sensitive dye. Fits of these maps to a passive cable model showed that the snail neurons are electrotonically rather compact. Given these features of our experimental system, the synaptic conductances derived with the nonisopotential model deviated from the estimates of the isopotential theory by about 13%. This discrepancy, although small, shows that even in electrotonically compact neurons coupled by weak synapses the impact of the neuritic cables on conductance estimates cannot be neglected. When applied to less compact and more strongly coupled cell pairs in vivo, our approach can supply the realistic estimates of synaptic conductances that are necessary for a better understanding of the role of electrical coupling in neural systems.

2017 ◽  
Author(s):  
Audrey J Marsh ◽  
Jennifer Carlisle Michel ◽  
Anisha P Adke ◽  
Emily L Heckman ◽  
Adam C Miller

AbstractNeuronal synaptic connections are electrical or chemical and together are essential to dynamically defining neural circuit function. While chemical synapses are well known for their biochemical complexity, electrical synapses are often viewed as comprised solely of neuronal gap junction channels that allow direct ionic and metabolic communication. However, associated with the gap junction channels are structures observed by electron microscopy called the Electrical Synapse Density (ESD). The ESD has been suggested to be critical for the formation and function of the electrical synapse, yet the biochemical makeup of these structures is poorly understood. Here we find that electrical synapse formation in vivo requires an intracellular scaffold called Tight Junction Protein 1b (Tjp1b). Tjp1b is localized to electrical synapses where it is required for the stabilization of the gap junction channels and for electrical synapse function. Strikingly, we find that Tjp1b protein localizes and functions asymmetrically, exclusively on the postsynaptic side of the synapse. Our findings support a novel model in which there is molecular asymmetry at the level of the intracellular scaffold that is required for building the electrical synapse. ESD molecular asymmetries may be a fundamental motif of all nervous systems and could support functional asymmetry at the electrical synapse.


2021 ◽  
Author(s):  
Sierra Palumbos ◽  
Rachel Skelton ◽  
Rebecca McWhirter ◽  
Amanda Mitchell ◽  
Isaiah Swann ◽  
...  

Electrical synapses are established between specific neurons and within distinct subcellular compartments, but the mechanisms that direct gap junction assembly in the nervous system are largely unknown. Here we show that a transcriptional program tunes cAMP signaling to direct the neuron-specific assembly and placement of electrical synapses in the C. elegans motor circuit. For these studies, we use live cell imaging to visualize electrical synapses in vivo and a novel optogenetic assay to confirm that they are functional. In VA motor neurons, the UNC-4 transcription factor blocks expression of cAMP antagonists that promote gap junction miswiring. In unc-4 mutants, VA electrical synapses are established with an alternative synaptic partner and are repositioned from the VA axon to soma. We show that cAMP counters these effects by driving gap junction trafficking into the VA axon for electrical synapse assembly. Thus, our experiments in an intact nervous system establish that cAMP regulates gap junction trafficking for the biogenesis of electrical synapses.


2004 ◽  
Vol 92 (1) ◽  
pp. 630-643 ◽  
Author(s):  
Andrew Y. Y. Tan ◽  
Li I. Zhang ◽  
Michael M. Merzenich ◽  
Christoph E. Schreiner

In primary auditory cortex (AI) neurons, tones typically evoke a brief depolarization, which can lead to spiking, followed by a long-lasting hyperpolarization. The extent to which the hyperpolarization is due to synaptic inhibition has remained unclear. Here we report in vivo whole cell voltage-clamp measurements of tone-evoked excitatory and inhibitory synaptic conductances of AI neurons of the pentobarbital-anesthetized rat. Tones evoke an increase of excitatory synaptic conductance, followed by an increase of inhibitory synaptic conductance. The synaptic conductances can account for the gross time course of the typical membrane potential response. Synaptic excitation and inhibition have the same frequency tuning. As tone intensity increases, the amplitudes of synaptic excitation and inhibition increase, and the latency of synaptic excitation decreases. Our data indicate that the interaction of synaptic excitation and inhibition shapes the time course and frequency tuning of the spike responses of AI neurons.


2021 ◽  
Vol 22 (22) ◽  
pp. 12138
Author(s):  
Huaixing Wang ◽  
Julie S. Haas

Two distinct types of neuronal activity result in long-term depression (LTD) of electrical synapses, with overlapping biochemical intracellular signaling pathways that link activity to synaptic strength, in electrically coupled neurons of the thalamic reticular nucleus (TRN). Because components of both signaling pathways can also be modulated by GABAB receptor activity, here we examined the impact of GABAB receptor activation on the two established inductors of LTD in electrical synapses. Recording from patched pairs of coupled rat neurons in vitro, we show that GABAB receptor inactivation itself induces a modest depression of electrical synapses and occludes LTD induction by either paired bursting or metabotropic glutamate receptor (mGluR) activation. GABAB activation also occludes LTD from either paired bursting or mGluR activation. Together, these results indicate that afferent sources of GABA, such as those from the forebrain or substantia nigra to the reticular nucleus, gate the induction of LTD from either neuronal activity or afferent glutamatergic receptor activation. These results add to a growing body of evidence that the regulation of thalamocortical transmission and sensory attention by TRN is modulated and controlled by other brain regions. Significance: We show that electrical synapse plasticity is gated by GABAB receptors in the thalamic reticular nucleus. This effect is a novel way for afferent GABAergic input from the basal ganglia to modulate thalamocortical relay and is a possible mediator of intra-TRN inhibitory effects.


2021 ◽  
Author(s):  
Robin De Schepper ◽  
Alice Geminiani ◽  
Stefano Masoli ◽  
Martina Francesca Rizza ◽  
Alberto Antonietti ◽  
...  

Abstract The cerebellar network is renowned for its regular architecture that has inspired foundational computational theories. However, the relationship between circuit structure, function and dynamics remained elusive. To tackle the issue, we have developed an advanced computational modeling framework that allowed us to reconstruct and simulate the structure and function of the mouse cerebellar cortex using morphologically realistic multi-compartmental neuron models. The cerebellar connectome was generated through appropriate connection rules, unifying a collection of scattered experimental data into a coherent construct and providing a new model-based ground-truth about circuit organization. Naturalistic background and sensory-burst stimulation were then used for functional validation against recordings in vivo, monitoring the impact of cellular mechanisms on signal propagation and spatio-temporal processing. Our simulations show, for the first time, how mossy fibers entrain the local neuronal microcircuit boosting the formation of columns of activity travelling from the granular to the molecular layer providing a new resource for the investigation of cerebellar computation.


2021 ◽  
Author(s):  
Robin Gilbert De Schepper ◽  
Alice Geminiani ◽  
Stefano Masoli ◽  
Martina Francesca Rizza ◽  
Alberto Antonietti ◽  
...  

Modelling brain networks with complex configuration and cellular properties requires a set of neuroinformatic tools and an organized staged workflow. We have therefore developed the Brain Scaffold Builder (BSB), a new modeling framework embedding multiple strategies for cell placement and connectivity and a flexible management of cellular and network mechanisms. With BSB, for the first time, the mouse cerebellar cortex was reconstructed and simulated at cellular resolution, using morphologically realistic multi-compartmental single-neuron models. Embedded connection rules allowed BSB to generate the cerebellar connectome, unifying a collection of scattered experimental data into a coherent construct. Naturalistic background and sensory-burst stimulation were used for functional validation against recordings in vivo, monitoring the impact of subcellular mechanisms on signal propagation and spatio-temporal processing and providing a new ground-truth about circuit organization for the prediction of neural dynamics.


2014 ◽  
Vol 1 (3) ◽  
pp. 3-7
Author(s):  
O. Zhukorskyy ◽  
O. Hulay

Aim. To estimate the impact of in vivo secretions of water plantain (Alisma plantago-aquatica) on the popula- tions of pathogenic bacteria Erysipelothrix rhusiopathiae. Methods. The plants were isolated from their natural conditions, the roots were washed from the substrate residues and cultivated in laboratory conditions for 10 days to heal the damage. Then the water was changed; seven days later the selected samples were sterilized using fi lters with 0.2 μm pore diameter. The dilution of water plantain root diffusates in the experimental samples was 1:10–1:10,000. The initial density of E. rhusiopathiae bacteria populations was the same for both experimental and control samples. The estimation of the results was conducted 48 hours later. Results. When the dilution of root diffusates was 1:10, the density of erysipelothrixes in the experimental samples was 11.26 times higher than that of the control, on average, the dilution of 1:100 − 6.16 times higher, 1:1000 – 3.22 times higher, 1:10,000 – 1.81 times higher, respectively. Conclusions. The plants of A. plantago-aquatica species are capable of affecting the populations of E. rhusiopathiae pathogenic bacteria via the secretion of biologically active substances into the environment. The consequences of this interaction are positive for the abovementioned bacteria, which is demon- strated by the increase in the density of their populations in the experiment compared to the control. The intensity of the stimulating effect on the populations of E. rhusiopathiae in the root diffusates of A. plantago-aquatica is re- ciprocally dependent on the degree of their dilution. The investigated impact of water plantain on erysipelothrixes should be related to the topical type of biocenotic connections, the formation of which between the test species in the ecosystems might promote maintaining the potential of natural focus of rabies. Keywords: Alisma plantago-aquatica, in vivo secretions, Erysipelothrix rhusiopathiae, population density, topical type of connections.


2016 ◽  
pp. 3564-3575 ◽  
Author(s):  
Ara Sergey Avetisyan

The efficiency of virtual cross sections method and MELS (Magneto Elastic Layered Systems) hypotheses application is shown on model problem about distribution of wave field in thin surface layers of waveguide when plane wave signal is propagating in it. The impact of surface non-smoothness on characteristics of propagation of high-frequency horizontally polarized wave signal in isotropic elastic half-space is studied. It is shown that the non-smoothness leads to strong distortion of the wave signal over the waveguide thickness and along wave signal propagation direction as well.  Numerical comparative analysis of change in amplitude and phase characteristics of obtained wave fields against roughness of weakly inhomogeneous surface of homogeneous elastic half-space surface is done by classical method and by proposed approach for different kind of non-smoothness.


Author(s):  
Hossam Ebaid ◽  
Mohamed Habila ◽  
Iftekhar Hassan ◽  
Jameel Al-Tamimi ◽  
Mohamed S. Omar ◽  
...  

Background: Hepatotoxicity remains an important clinical challenge. Hepatotoxicity observed in response to toxins and hazardous chemicals may be alleviated by delivery of the curcumin in silver nanoparticles (AgNPs-curcumin). In this study, we examined the impact of AgNPs-curcumin in a mouse model of carbon tetrachloride (CCl4)-induced hepatic injury. Methods: Male C57BL/6 mice were divided into three groups (n=8 per group). Mice in group 1 were treated with vehicle control alone, while mice in Group 2 received a single intraperitoneal injection of 1 ml/kg CCl4 in liquid paraffin (1:1 v/v). Mice in group 3 were treated with 2.5 mg/kg AgNPs-curcumin twice per week for three weeks after the CCl4 challenge. Results: Administration of CCL4 resulted in oxidative dysregulation, including significant reductions in reduced glutathione and concomitant elevations in the level of malondialdehyde (MDA). CCL4 challenge also resulted in elevated levels of serum aspartate transaminase (AST) and alanine transaminase (ALT); these findings were associated with the destruction of hepatic tissues. Treatment with AgNPs-curcumin prevented oxidative imbalance, hepatic dysfunction, and tissue destruction. A comet assay revealed that CCl4 challenge resulted in significant DNA damage as documented by a 70% increase in nuclear DNA tail-length; treatment with AgNPs-curcumin inhibited the CCL4-mediated increase in nuclear DNA tail-length by 34%. Conclusion: Administration of AgNPs-curcumin resulted in significant antioxidant activity in vivo. This agent has the potential to prevent the hepatic tissue destruction and DNA damage that results from direct exposure to CCL4.


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