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

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

Analysis of Coplanar On-Chip Interconnects on Lossy Semiconducting Substrates

In this paper, a method for analysis and modeling of coplanar transmission interconnect lines that are placed on top of silicon-silicon oxide substrates is presented. The potential function is expressed by series expansions in terms of solutions of the Laplace equation for each homogeneous region of layered structure. The expansion coefficients of different series are related to each other and to potentials applied to the conductors via boundary conditions. In the plane of conductors, boundary conditions are satisfied at Nd discrete points with Nd being equal to the number of terms in the series expansions. The resulting system of inhomogeneous linear equations is solved by matrix inversion. No iterations are required. A discussion of the calculated line admittance parameters as functions of width of conductors, thickness of the layers, and frequency is given. The interconnect capacitance and conductance per unit length results are given and compared with those obtained using full wave solutions, and good agreement have been obtained in all the cases treated

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

Proximity effects and Andreev reflection in mesoscopic SNS junction with perfect NS interfaces

Low temperature transport measurements on superconducting film - normal metal wire - superconducting film (SNS) junctions fabricated on the basis of 6 nm thick superconducting polycrystalline PtSi films are reported. The structures with the normal metal wires of two different lengths L=1.5 $\mu$m and L=6$\mu$m and the same widths W=0.3$\mu$m are studied. Zero bias resistance dip related to pair current proximity effect is observed for all junctions whereas the subharmonic energy gap structure originating from phase coherent multiple Andreev reflections have occurs only in the SNS junctions with short wires.Comment: ReVTex, 4 pages, 4 eps figures include

EEG microstates: Functional significance and short-term test-retest reliability

Appendix A: Supplementary data to this article can be found online at https://doi. org/10.1016/j.ynirp.2022.100089.Copyright /© 2022 The Authors. EEG signal power, may have clinical relevance; however, their functional significance and test-retest reliability remain unclear. To investigate the functional significance of the canonical EEG microstate classes and their pairwise transitions, and to establish their within-session test-retest reliability, we recorded 36-channel EEGs in 20 healthy volunteers during three eyes-closed conditions: mind-wandering, verbalization (silently repeating the word ‘square’ every 2 s), and visualization (visualizing a square every 2 s). Each condition lasted 3 min and the sequence of three conditions was repeated four times (two runs of two sequence repetitions). The participants' alertness and their sense of effort during the experiment were rated using visual-analogue scales. The EEG data were 2–20 Hz bandpass-filtered and analysed into the four canonical microstate classes: A, B, C, and D. EEG microstate classes C and D were persistently more dominant than classes A and B in all conditions. Of the first-order microstate parameters, average microstate duration was most reliable. The duration of class D microstate was longer during mind-wandering (106.8 ms) than verbalization (102.2 ms) or visualization (99.8 ms), with a concomitantly higher coverage (36.4% vs. 34.7% and 35.2%), but otherwise there was no clear association of the four microstate classes to particular mental states. The test-retest reliability was higher at the beginning of each run, together with higher average alpha power and subjective ratings of alertness. Only the transitions between classes C and D (from C to D in particular) were significantly higher than what would be expected from the respective microstates' occurrences. The transition probabilities, however, did not distinguish between conditions, and their test-retest reliability was overall lower than that of the first-order parameters such as duration and coverage. Further studies are needed to establish the functional significance of the canonical EEG microstate classes. This might be more fruitfully achieved by looking at their complex syntax beyond pairwise transitions. To ensure greater test-retest reliability of microstate parameters, study designs should allow for shorter experimental runs with regular breaks, particularly when using EEG microstates as clinical biomarkers.BIAL Foundation (grant number: 183/16)

The effect of non-specific LTD on pattern recognition in cerebellar Purkinje cells

© 2010 Safaryan et al; licensee BioMed Central Ltd.Poster presented at CNS 2010Peer reviewe

Endogenous cholinergic inputs and local circuit mechanisms govern the phasic mesolimbic dopamine response to nicotine

Nicotine exerts its reinforcing action by stimulating nicotinic acetylcholine receptors (nAChRs) and boosting dopamine (DA) output from the ventral tegmental area (VTA). Recent data have led to a debate about the principal pathway of nicotine action: direct stimulation of the DAergic cells through nAChR activation, or disinhibition mediated through desensitization of nAChRs on GABAergic interneurons. We use a computational model of the VTA circuitry and nAChR function to shed light on this issue. Our model illustrates that the α4β2-containing nAChRs either on DA or GABA cells can mediate the acute effects of nicotine. We account for in vitro as well as in vivo data, and predict the conditions necessary for either direct stimulation or disinhibition to be at the origin of DA activity increases. We propose key experiments to disentangle the contribution of both mechanisms. We show that the rate of endogenous acetylcholine input crucially determines the evoked DA response for both mechanisms. Together our results delineate the mechanisms by which the VTA mediates the acute rewarding properties of nicotine and suggest an acetylcholine dependence hypothesis for nicotine reinforcement.Peer reviewe

Quantitative Organization of GABAergic Synapses in the Molecular Layer of the Mouse Cerebellar Cortex

In the cerebellar cortex, interneurons of the molecular layer (stellate and basket cells) provide GABAergic input to Purkinje cells, as well as to each other and possibly to other interneurons. GABAergic inhibition in the molecular layer has mainly been investigated at the interneuron to Purkinje cell synapse. In this study, we used complementary subtractive strategies to quantitatively assess the ratio of GABAergic synapses on Purkinje cell dendrites versus those on interneurons. We generated a mouse model in which the GABAA receptor α1 subunit (GABAARα1) was selectively removed from Purkinje cells using the Cre/loxP system. Deletion of the α1 subunit resulted in a complete loss of GABAAR aggregates from Purkinje cells, allowing us to determine the density of GABAAR clusters in interneurons. In a complementary approach, we determined the density of GABA synapses impinging on Purkinje cells using α-dystroglycan as a specific marker of inhibitory postsynaptic sites. Combining these inverse approaches, we found that synapses received by interneurons represent approximately 40% of all GABAergic synapses in the molecular layer. Notably, this proportion was stable during postnatal development, indicating synchronized synaptogenesis. Based on the pure quantity of GABAergic synapses onto interneurons, we propose that mutual inhibition must play an important, yet largely neglected, computational role in the cerebellar cortex