Subthreshold dynamics of the neural membrane potential driven by stochastic synaptic input

In the cerebral cortex, neurons are subject to a continuous bombardment of synaptic inputs originating from the network's background activity. This leads to ongoing, mostly subthreshold membrane dynamics that depends on the statistics of the background activity and of the synapses made on a neuron. Subthreshold membrane polarization is, in turn, a potent modulator of neural responses. The present paper analyzes the subthreshold dynamics of the neural membrane potential driven by synaptic inputs of stationary statistics. Synaptic inputs are considered in linear interaction. The analysis identifies regimes of input statistics which give rise to stationary, fluctuating, oscillatory, and unstable dynamics. In particular, I show that (i) mere noise inputs can drive the membrane potential into sustained, quasiperiodic oscillations (noise-driven oscillations), in the absence of a stimulus-derived, intraneural, or network pacemaker; (ii) adding hyperpolarizing to depolarizing synaptic input can increase neural activity (hyperpolarization-induced activity), in the absence of hyperpolarization-activated currents

Democratization in a passive dendritic tree : an analytical investigation

One way to achieve amplification of distal synaptic inputs on a dendritic tree is to scale the amplitude and/or duration of the synaptic conductance with its distance from the soma. This is an example of what is often referred to as “dendritic democracy”. Although well studied experimentally, to date this phenomenon has not been thoroughly explored from a mathematical perspective. In this paper we adopt a passive model of a dendritic tree with distributed excitatory synaptic conductances and analyze a number of key measures of democracy. In particular, via moment methods we derive laws for the transport, from synapse to soma, of strength, characteristic time, and dispersion. These laws lead immediately to synaptic scalings that overcome attenuation with distance. We follow this with a Neumann approximation of Green’s representation that readily produces the synaptic scaling that democratizes the peak somatic voltage response. Results are obtained for both idealized geometries and for the more realistic geometry of a rat CA1 pyramidal cell. For each measure of democratization we produce and contrast the synaptic scaling associated with treating the synapse as either a conductance change or a current injection. We find that our respective scalings agree up to a critical distance from the soma and we reveal how this critical distance decreases with decreasing branch radius

High-threshold and low-overhead fault-tolerant quantum memory

Quantum error correction becomes a practical possibility only if the physical error rate is below a threshold value that depends on a particular quantum code, syndrome measurement circuit, and a decoding algorithm. Here we present an end-to-end quantum error correction protocol that implements fault-tolerant memory based on a family of LDPC codes with a high encoding rate that achieves an error threshold of $0.8\%$ for the standard circuit-based noise model. This is on par with the surface code which has remained an uncontested leader in terms of its high error threshold for nearly 20 years. The full syndrome measurement cycle for a length-$n$ code in our family requires $n$ ancillary qubits and a depth-7 circuit composed of nearest-neighbor CNOT gates. The required qubit connectivity is a degree-6 graph that consists of two edge-disjoint planar subgraphs. As a concrete example, we show that 12 logical qubits can be preserved for ten million syndrome cycles using 288 physical qubits in total, assuming the physical error rate of $0.1\%$. We argue that achieving the same level of error suppression on 12 logical qubits with the surface code would require more than 4000 physical qubits. Our findings bring demonstrations of a low-overhead fault-tolerant quantum memory within the reach of near-term quantum processors

What we talk about when we talk about capacitance measured with the voltage-clamp step method

Capacitance is a fundamental neuronal property. One common way to measure capacitance is to deliver a small voltage-clamp step that is long enough for the clamp current to come to steady state, and then to divide the integrated transient charge by the voltage-clamp step size. In an isopotential neuron, this method is known to measure the total cell capacitance. However, in a cell that is not isopotential, this measures only a fraction of the total capacitance. This has generally been thought of as measuring the capacitance of the “well-clamped” part of the membrane, but the exact meaning of this has been unclear. Here, we show that the capacitance measured in this way is a weighted sum of the total capacitance, where the weight for a given small patch of membrane is determined by the voltage deflection at that patch, as a fraction of the voltage-clamp step size. This quantifies precisely what it means to measure the capacitance of the “well-clamped” part of the neuron. Furthermore, it reveals that the voltage-clamp step method measures a well-defined quantity, one that may be more useful than the total cell capacitance for normalizing conductances measured in voltage-clamp in nonisopotential cells

Model of Low-pass Filtering of Local Field Potentials in Brain Tissue

Local field potentials (LFPs) are routinely measured experimentally in brain tissue, and exhibit strong low-pass frequency filtering properties, with high frequencies (such as action potentials) being visible only at very short distances ($\approx$10~$\mu m$) from the recording electrode. Understanding this filtering is crucial to relate LFP signals with neuronal activity, but not much is known about the exact mechanisms underlying this low-pass filtering. In this paper, we investigate a possible biophysical mechanism for the low-pass filtering properties of LFPs. We investigate the propagation of electric fields and its frequency dependence close to the current source, i.e. at length scales in the order of average interneuronal distance. We take into account the presence of a high density of cellular membranes around current sources, such as glial cells. By considering them as passive cells, we show that under the influence of the electric source field, they respond by polarisation, i.e., creation of an induced field. Because of the finite velocity of ionic charge movement, this polarization will not be instantaneous. Consequently, the induced electric field will be frequency-dependent, and much reduced for high frequencies. Our model establishes that with respect to frequency attenuation properties, this situation is analogous to an equivalent RC-circuit, or better a system of coupled RC-circuits. We present a number of numerical simulations of induced electric field for biologically realistic values of parameters, and show this frequency filtering effect as well as the attenuation of extracellular potentials with distance. We suggest that induced electric fields in passive cells surrounding neurons is the physical origin of frequency filtering properties of LFPs.Comment: 10 figs, revised tex file and revised fig

Post-thaw development of in vitro produced buffalo embryos cryopreserved by cytoskeletal stabilization and vitrification

The present study was conducted to examine post-thaw in vitro developmental competence of buffalo embryos cryopreserved by cytoskeletal stabilization and vitrification. In vitro produced embryos were incubated with a medium containing cytochalasin-b (cyto-b) in a CO2 incubator for 40 min for microfilament stabilization and were cryopreserved by a two-step vitrification method at 24℃ in the presence of cyto-b. Initially, the embryos were exposed to 10% ethylene glycol (EG) and 10% dimethylsulfoxide (DMSO) in a base medium for 4 min. After the initial exposure, the embryos were transferred to a 7 µl drop of 25% EG and 25% DMSO in base medium and 0.3 M sucrose for 45 sec. After warming, the embryos were cultured in vitro for 72 h. The post-thaw in vitro developmental competence of the cyto-b-treated embryos did not differ significantly from those vitrified without cyto-b treatment. The hatching rates of morulae vitrified without cyto-b treatment was significantly lower than the non-vitrified control. However, the hatching rate of cyto-b-treated vitrified morulae did not differ significantly from the non-vitrified control. This study demonstrates that freezing of buffalo embryos by cytoskeletal stabilization and vitrification is a reliable method for long-term preservation

A missing dimension in measures of vaccination impacts

Immunological protection, acquired from either natural infection or vaccination, varies among hosts, reflecting underlying biological variation and affecting population-level protection. Owing to the nature of resistance mechanisms, distributions of susceptibility and protection entangle with pathogen dose in a way that can be decoupled by adequately representing the dose dimension. Any infectious processes must depend in some fashion on dose, and empirical evidence exists for an effect of exposure dose on the probability of transmission to mumps-vaccinated hosts [1], the case-fatality ratio of measles [2], and the probability of infection and, given infection, of symptoms in cholera [3]. Extreme distributions of vaccine protection have been termed leaky (partially protects all hosts) and all-or-nothing (totally protects a proportion of hosts) [4]. These distributions can be distinguished in vaccine field trials from the time dependence of infections [5]. Frailty mixing models have also been proposed to estimate the distribution of protection from time to event data [6], [7], although the results are not comparable across regions unless there is explicit control for baseline transmission [8]. Distributions of host susceptibility and acquired protection can be estimated from dose-response data generated under controlled experimental conditions [9]–[11] and natural settings [12], [13]. These distributions can guide research on mechanisms of protection, as well as enable model validity across the entire range of transmission intensities. We argue for a shift to a dose-dimension paradigm in infectious disease science and community health

Optimization principles of dendritic structure

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Acute effects of insulin and insulin-induced hypoglycaemia on carotid body chemoreceptor activity and cardiorespiratory responses in dogs

Funding: Silvia V. Conde declares that Galvani Bioelectronics provided funds to support their work associated with Type 2 diabetic project.New Findings: What is the central question of this study? What are the effects of insulin and insulin-induced hypoglycaemia on carotid body chemoreceptor activity in vivo and how do carotid body chemoreceptor stimulation-mediated cardiorespiratory responses in beagle dogs compare during euglycaemia and insulin-induced hypoglycaemia? What is the main finding and its importance? Intracarotid insulin administration leads to sustained increase in carotid body chemoreceptor activity and respiratory response with significant cardiovascular effects. Insulin-induced hypoglycaemia exacerbated NaCN-mediated carotid body chemoreceptor activity and respiratory response with enhanced cardiovascular reflex response. These findings suggest that insulin-induced hypoglycaemia augments the carotid body chemoreceptors to initiate the adaptive counter-regulatory responses to restore the normoglycaemic condition. Abstract: The carotid body chemoreceptors (CBC) play an important role in the adaptive counter-regulatory response to hypoglycaemia by evoking the CBC-mediated sympathetic neuronal system to restore normoglycaemia. Ex vivo studies have shown varied responses of insulin-induced hypoglycaemia on CBC function, and several in vivo studies have indirectly established the role of CBCs in restoring normoglycaemia in both animals and humans. However, a direct effect of insulin and/or insulin-induced hypoglycaemia on CBC activity is not established in animal models. Therefore, the aim of this study was to evaluate in vivo effects of insulin and insulin-induced hypoglycaemia on CBC activity and cardiorespiration in a preclinical large animal model. The carotid sinus nerve (CSN) activity and cardiorespiratory responses to sodium cyanide (NaCN; 25 µg/kg) were compared before (euglycaemic) and after (hypoglycaemic) intracarotid administration of insulin (12.5–100 µU/dogs) in beagle dogs. Insulin administration increased CSN activity and minute ventilation ((Formula presented.) E) with significant (P < 0.0001) effects on heart rate and blood pressure. Insulin-mediated effects on CSN and cardiorespiration were sustained and the change in (Formula presented.) E was driven by tidal volume only. Insulin significantly (P < 0.0001) lowered blood glucose level. NaCN-mediated CSN activity and (Formula presented.) E were significantly (P < 0.0001) augmented during insulin-induced hypoglycaemia. The augmented (Formula presented.) E was primarily driven by respiratory frequency and partially by tidal volume. The cardiovascular reflex response mediated through CBC stimulation was significantly (P < 0.0001) exacerbated during insulin-induced hypoglycaemia. Collectively, these results demonstrate direct effects of insulin and insulin-induced hypoglycaemia on CBC chemosensitivity to potentiate CBC-mediated neuroregulatory pathways to initiate adaptive neuroendocrine and cardiorespiratory counter-regulatory responses to restore normoglycaemia.publishersversionepub_ahead_of_prin