An Isotonic Model of Neuron Swelling Based on Co-Transport of Salt and Water

© 2023 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)Neurons spend most of their energy building ion gradients across the cell membrane. During energy deprivation the neurons swell, and the concomitant mixing of their ions is commonly assumed to lead toward a Donnan equilibrium, at which the concentration gradients of all permeant ion species have the same Nernst potential. This Donnan equilibrium, however, is not isotonic, as the total concentration of solute will be greater inside than outside the neurons. The present theoretical paper, in contrast, proposes that neurons follow a path along which they swell quasi-isotonically by co-transporting water and ions. The final neuronal volume on the path is taken that at which the concentration of impermeant anions in the shrinking extracellular space equals that inside the swelling neurons. At this final state, which is also a Donnan equilibrium, all permeant ions can mix completely, and their Nernst potentials vanish. This final state is isotonic and electro-neutral, as are all intermediate states along this path. The path is in principle reversible, and maximizes the work of mixing.Peer reviewe

Effect of extracellular volume on the energy stored in transmembrane concentration gradients

© 2021 American Physical Society. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1103/PhysRevE.104.044409The amount of energy that can be retrieved from a concentration gradient across a membrane separating two compartments depends on the relative size of the compartments. Having a larger low-concentration compartment is in general beneficial. It is shown here analytically that the retrieved energy further increases when the high-concentration compartment shrinks during the mixing process, and a general formula is derived for the energy when the ratio of transported solvent to solute varies. These calculations are then applied to the interstitial compartment of the brain, which is rich in and ions and poor in . The reported shrinkage of this compartment, and swelling of the neurons, during oxygen deprivation is shown to enhance the energy recovered from NaCl entering the neurons. The slight loss of energy on the part of can be compensated for by the uptake of ions by glial cells. In conclusion, the present study proposes that the reported fluctuations in the size of the interstitial compartment of the brain (expansion during sleep and contraction during oxygen deprivation) optimize the amount of energy that neurons can store in, and retrieve from, their ionic concentration gradients.Peer reviewedFinal Accepted Versio

An Interneuron Circuit Reproducing Essential Spectral Features of Field Potentials

This document is the Accepted Manuscript version of the following article: Reinoud Maex, ‘An Interneuron Circuit Reproducing Essential Spectral Features of Field Potentials’, Neural Computation, March 2018. Under embargo until 22 June 2018. The final, definitive version of this paper is available online at doi: https://doi.org/10.1162/NECO_a_01068. © 2018 Massachusetts Institute of Technology. Content in the UH Research Archive is made available for personal research, educational, and non-commercial purposes only. Unless otherwise stated, all content is protected by copyright, and in the absence of an open license, permissions for further re-use should be sought from the publisher, the author, or other copyright holder.Recent advances in engineering and signal processing have renewed the interest in invasive and surface brain recordings, yet many features of cortical field potentials remain incompletely understood. In the present computational study, we show that a model circuit of interneurons, coupled via both GABA(A) receptor synapses and electrical synapses, reproduces many essential features of the power spectrum of local field potential (LFP) recordings, such as 1/f power scaling at low frequency (< 10 Hz) , power accumulation in the γ-frequency band (30–100 Hz), and a robust α rhythm in the absence of stimulation. The low-frequency 1/f power scaling depends on strong reciprocal inhibition, whereas the α rhythm is generated by electrical coupling of intrinsically active neurons. As in previous studies, the γ power arises through the amplifica- tion of single-neuron spectral properties, owing to the refractory period, by parameters that favour neuronal synchrony, such as delayed inhibition. The present study also confirms that both synaptic and voltage-gated membrane currents substantially contribute to the LFP, and that high-frequency signals such as action potentials quickly taper off with distance. Given the ubiquity of electrically coupled interneuron circuits in the mammalian brain, they may be major determinants of the recorded potentials.Peer reviewe

Determinants of gain modulation enabled by short-term depression at an inhibitory cerebellar synapse

Abstract from the 23rd Annual Computational Neuroscience Meeting: CNS 2014. © 2014 Bampasakis et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedNeurons adapt rapidly the slope, also known as gain, of their input-output function to time-varying conditions. Gain modulation is a prominent mechanism in many brain processes, such as auditory processing and attention scaling of orientation tuning curves.Peer reviewe

A potential role for the cerebellar nuclei in absence seizures

© 2013 Alva et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Poster presented ar CNS 2013Non peer reviewe

Understanding the role α7 nicotinic receptors play in dopamine efflux in nucleus accumbens

This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.Neuronal nicotinic acetylcholine receptors (NNRs) of the α7 subtype have been shown to contribute to the release of dopamine in the nucleus accumbens. The site of action and the underlying mechanism, however, are unclear. Here we applied a circuit modeling approach, supported by electrochemical in vivo recordings, to clarify this issue. Modeling revealed two potential mechanisms for the drop in accumbal dopamine efflux evoked by the selective α7 partial agonist TC-7020. TC-7020 could desensitize α7 NNRs located predominantly on dopamine neurons or glutamatergic afferents to them or, alternatively, activate α7 NNRs located on the glutamatergic afferents to GABAergic interneurons in the ventral tegmental area. Only the model based on desensitization, however, was able to explain the neutralizing effect of coapplied PNU-120596, a positive allosteric modulator. According to our results, the most likely sites of action are the preterminal α7 NNRs controlling glutamate release from cortical afferents to the nucleus accumbens. These findings offer a rationale for the further investigation of α7 NNR agonists as therapy for diseases associated with enhanced mesolimbic dopaminergic tone, such as schizophrenia and addiction.Peer reviewe

Temporal integration and 1/f power scaling in a circuit model of cerebellar interneurons

This document is the Accepted Manuscript version of a published work that appeared in final form in Journal of Neurophysiology after peer review and technical editing by the publisher. Under embargo until 1 July 2018. To access the final edited and published work see: https://doi.org/10.1152/jn.00789.2016.Inhibitory interneurons interconnected via electrical and chemical (GABAA receptor) synapses form extensive circuits in several brain regions. They are thought to be involved in timing and synchronization through fast feedforward control of principal neurons. Theoretical studies have shown, however, that whereas self-inhibition does indeed reduce response duration, lateral inhibition, in contrast, may generate slow response components through a process of gradual disinhibition. Here we simulated a circuit of interneurons (stellate and basket cells) of the molecular layer of the cerebellar cortex and observed circuit time constants that could rise, depending on parameter values, to >1 s. The integration time scaled both with the strength of inhibition, vanishing completely when inhibition was blocked, and with the average connection distance, which determined the balance between lateral and self-inhibition. Electrical synapses could further enhance the integration time by limiting heterogeneity among the interneurons and by introducing a slow capacitive current. The model can explain several observations, such as the slow time course of OFF-beam inhibition, the phase lag of interneurons during vestibular rotation, or the phase lead of Purkinje cells. Interestingly, the interneuron spike trains displayed power that scaled approximately as 1/f at low frequencies. In conclusion, stellate and basket cells in cerebellar cortex, and interneuron circuits in general, may not only provide fast inhibition to principal cells but also act as temporal integrators that build a very short-term memory.NEW & NOTEWORTHY The most common function attributed to inhibitory interneurons is feedforward control of principal neurons. In many brain regions, however, the interneurons are densely interconnected via both chemical and electrical synapses but the function of this coupling is largely unknown. Based on large-scale simulations of an interneuron circuit of cerebellar cortex, we propose that this coupling enhances the integration time constant, and hence the memory trace, of the circuit.Peer reviewe

The beneficial effects of non-specific synaptic plasticity for pattern recognition in auto-associative memory

© 2011 Calcraft et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Poster presented at CNS 2011Non peer reviewe

Non-specific LTD at parallel fibre - Purkinje cell synapses in cerebellar cortex provides robustness against local spatial noise during pattern recognition

© 2011 Safaryan et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citedPoster presented at CNS 2011Peer reviewe