Biology subjects

Celikel, T.

Publications and source records attributed to Celikel, T..

26 records · Page 2Linked to original sources

bioRxiv2019

Assessing the utility of MAGNETO to control neuronal excitability in the somatosensory cortex

Magnetic neuromodulation has outstanding promise for the development of novel neural interfaces without direct physical intervention with the brain. Here we tested the utility of Magneto in the adult somatosensory cortex by performing whole-cell intracellular recordings in vitro and extracellular recordings in freely moving mice. Results show that magnetic stimulation does not alter subthreshold membrane excitability or contribute to the generation of action potentials in virally transduced neurons expressing Magneto.

neuroscience↗

bioRxiv2019

Development of adaptive motor control for tactile navigation

Navigation is a result of complex sensorimotor computation which requires integration of sensory information in allocentric and egocentric coordinates as the brain computes a motor plan to drive navigation. In this active sensing process, motor commands are adaptively regulated based on prior sensory information. In the darkness, rodents commonly rely on their tactile senses, in particular to their whiskers, to gather the necessary sensory information and instruct navigation. Previous research has shown that rodents can process whisker input to guide mobility even prior to whisking onset by the end of the second postnatal week, however, when and how adaptive sensorimotor control of whisker position matures is still not known. Here, we addressed this question in rats longitudinally as animals searched for a stationary target in darkness. The results showed that juvenile rats perform object localization by controlling their body, but not whisker position, based on the expected location of the target. Adaptive, closed-loop, control of whisker position matures only after the third postnatal week. Computational modeling of the active whisking showed the emergence of the closed-loop control of whisker position and reactive retraction, i.e. whisker retraction that ensures the constancy of duration of tactile sampling, facilitate the maturation of sensorimotor exploration strategies during active sensing. These results argue that adaptive motor control of body and whiskers develop sequentially, and sensorimotor control of whisker position emerges later in postnatal development upon the maturation of intracortical sensorimotor circuits.

neuroscience↗

bioRxiv2019

Serotonergic development of active sensing

Active sensing requires adaptive motor (positional) control of sensory organs based on contextual, sensory and task requirements, and develops postnatally after the maturation of intracortical circuits. Alterations in sensorimotor network connectivity during this period are likely to impact sensorimotor computation also in adulthood. Serotonin is among the cardinal developmental regulators of network formation, thus changing the serotonergic drive might have consequences for the emergence and maturation of sensorimotor control. Here we tested this hypothesis on an object localization task by quantifying the motor control dynamics of whiskers during tactile navigation. The results showed that sustained alterations in serotonergic signaling in serotonin transporter knockout rats, or the transient pharmacological inactivation of the transporter during early postnatal development, impairs the emergence of adaptive motor control of whisker position based on recent sensory information. A direct outcome of this altered motor control is that the mechanical force transmitted to whisker follicles upon contact is reduced, suggesting that increased excitability observed upon altered serotonergic signaling is not due to increased synaptic drive originating from the periphery upon whisker contact. These results argue that postnatal development of adaptive motor control requires intact serotonergic signaling and that even its transient dysregulation during early postnatal development causes lasting sensorimotor impairments in adulthood.

neuroscience↗

bioRxiv2019

PASER for automated analysis of neural signals recorded in pulsating magnetic fields

Thanks to the advancements in multichannel intracranial neural recordings, magnetic neuroimaging and magnetic neurostimulation techniques (including magnetogenetics), it is now possible to perform large-scale high-throughput neural recordings while imaging or controlling neural activity in a magnetic field. Analysis of neural recordings performed in a switching magnetic field, however, is not a trivial task as gradient and pulse artefacts interfere with the unit isolation. Here we introduce a toolbox called PASER, Processing and Analysis Schemes for Extracellular Recordings, that performs automated denoising, artefact removal, quality control of electrical recordings, unit classification and visualization. PASER is written in MATLAB and modular by design. The current version integrates with third party applications to provide additional functionality, including data import, spike sorting and the analysis of local field potentials. After the description of the toolbox, we evaluate 9 different spike sorting algorithms based on computational cost, unit yield, unit quality and clustering reliability across varying conditions including self-blurring and noise-reversal. Implementation of the best performing spike sorting algorithm (KiloSort) in the default version of the PASER provides the end user with a fully automated pipeline for quantitative analysis of broadband extracellular signals. PASER can be integrated with any established pipeline that sample neural activity with intracranial electrodes. Unlike the existing algorithmic solutions, PASER provides an end-to-end solution for neural recordings made in switching magnetic fields independent from the number of electrodes and the duration of recordings, thus enables high-throughput analysis of neural activity in a wide range of electro-magnetic recording conditions.

neuroscience↗

bioRxiv2018

Real-time contextual feedback for close-loop control of navigation

ObjectiveClose-loop control of brain and behavior will benefit from real-time detection of behavioral events to enable low-latency communication with peripheral devices. In animal experiments, this is typically achieved by using sparsely distributed (embedded) sensors that detect animal presence in select regions of interest. High-speed cameras provide high-density sampling across large arenas, capturing the richness of animal behavior, however, the image processing bottleneck prohibits real-time feedback in the context of rapidly evolving behaviors.\n\nApproachHere we developed an open-source software, named PolyTouch, to track animal behavior in large arenas and provide rapid close-loop feedback in ~5.7 ms, ie. average latency from the detection of an event to analog stimulus delivery, e.g. auditory tone, TTL pulse, when tracking a single body. This stand-alone software is written in JAVA. The included wrapper for MATLAB provides experimental flexibility for data acquisition, analysis and visualization.\n\nMain resultsAs a proof-of-principle application we deployed the PolyTouch for place awareness training. A user-defined portion of the arena was used as a virtual target; visit (or approach) to the target triggered auditory feedback. We show that mice develop awareness to virtual spaces, tend to stay shorter and move faster when they reside in the virtual target zone if their visits are coupled to relatively high stimulus intensity ([≥]49dB). Thus, close-loop presentation of perceived aversive feedback is sufficient to condition mice to avoid virtual targets within the span of a single session (~20min).\n\nSignificanceNeuromodulation techniques now allow control of neural activity in a cell-type specific manner in spiking resolution. Using animal behavior to drive closed-loop control of neural activity would help to address the neural basis of behavioral state and environmental context-dependent information processing in the brain.

animal behavior and cognition↗

bioRxiv2018

A databank for intracellular electrophysiological mapping of the adult somatosensory cortex

BackgroundNeurons in the supragranular layers of the somatosensory cortex integrate sensory (bottom-up) and cognitive/perceptual (top-down) information as they orchestrate communication across cortical columns. It has been inferred, based on intracellular recordings from juvenile animals, that supragranular neurons are electrically mature by the fourth postnatal week. However, the dynamics of the neuronal integration in the adulthood is largely unknown. Electrophysiological characterization of the active properties of these neurons throughout adulthood will help to address the biophysical and computational principles of the neuronal integration.\n\nFindingsHere we provide a database of whole-cell intracellular recordings from 315 neurons located in the supragranular layers (L2/3) of the primary somatosensory cortex in adult mice (9-45 weeks old) from both sexes (females, N=195; males, N=120). Data include 361 somatic current-clamp (CC) and 476 voltage-clamp (VC) experiments, recorded using a step-and-hold protocol (CC, N=257; VC, N=46), frozen noise injections (CC, N=104) and triangular voltage sweeps (VC, 10 (N=132), 50 (N=146) and 100 ms (N=152)), from regular spiking (N=169) and fast-spiking neurons (N=66).\n\nConclusionsThe data can be used to systematically study the properties of somatic integration, and the principles of action potential generation across sexes and across electrically characterized neuronal classes in adulthood. Understanding the principles of the somatic transformation of postsynaptic potentials into action potentials will shed light onto the computational principles of intracellular information transfer in single neurons and information processing in neuronal networks, helping to recreate neuronal functions in artificial systems.

neuroscience↗

bioRxiv2017

Molecules of map plasticity in the somatosensory cortex

Sensory maps are representations of the sensory epithelia in the brain. Despite the intuitive explanatory power behind sensory maps as being neuronal precursors to sensory perception, and sensory cortical plasticity as a neural correlate of perceptual learning, molecular mechanisms that regulate map plasticity are not well understood. Here we perform a meta-analysis of transcriptional and translational changes during altered whisker use to nominate the major molecular correlates of experience-dependent map plasticity in the barrel cortex. We argue that brain plasticity is a systems level response, involving all cell classes, from neuron and glia to non-neuronal cells including endothelia. Using molecular pathway analysis, we further propose a gene regulatory network that could couple activity dependent changes in neurons to adaptive changes in neurovasculature, and finally we show that transcriptional regulations observed in major brain disorders target genes that are modulated by altered sensory experience. Thus understanding the molecular mechanisms of experience-dependent plasticity of sensory maps might help to unravel the cellular events that shape brain plasticity in health and disease.\n\nHighlightsO_LIExperience alters gene transcription in all major cell types of the brain\nC_LIO_LIGene expression profile during brain plasticity is cell-type specific\nC_LIO_LITemporal profile of gene expression is dynamic, regulated by recent experience\nC_LIO_LINeural activity-dependent gene regulation might cause neurovascular reorganization\nC_LIO_LIGenes that are regulated by experience are commonly dysregulated in brain disorders\nC_LI

neuroscience↗

bioRxiv2017

Neocortical microdissection at columnar and laminar resolution for molecular interrogation

The heterogeneous organization of the mammalian neocortex poses a challenge to elucidate the molecular mechanisms underlying its physiological processes. Although high-throughput molecular methods are increasingly deployed in neuroscience, their anatomical specificity is often lacking. Here we introduce a targeted microdissection technique that enables extraction of high-quality RNA and proteins at high anatomical resolution from acutely prepared brain slices. We exemplify its utility by isolating single cortical columns and laminae from the mouse primary somatosensory (barrel) cortex. Tissues can be isolated from living slices in minutes, and the extracted RNA and protein are of sufficient quantity and quality to be used for RNA-sequencing and mass spectrometry. This technique will help to increase the anatomical specificity of molecular studies of the neocortex, and the brain in general as it is applicable to any brain structure that can be identified using optical landmarks in living slices.

neuroscience↗