scholarly journals Influence of data sampling methods on the representation of neural spiking activity in vivo

2022 ◽  
Author(s):  
Meike E van der Heijden ◽  
Amanda M Brown ◽  
Roy V Sillitoe
Keyword(s):  
Firing Rate ◽  
Single Neuron ◽  
Cerebellar Nuclei ◽  
Group Differences ◽  
Data Sampling ◽  
Disease States ◽  
Neural Spiking ◽  
Single Unit Recordings ◽  
Firing Properties

In vivo single-unit recordings distinguish the basal spiking properties of neurons in different experimental settings and disease states. Here, we examined over 300 spike trains recorded from Purkinje cells and cerebellar nuclei neurons to test whether data sampling approaches influence the extraction of rich descriptors of firing properties. Our analyses included neurons recorded in awake and anesthetized control mice, as well as disease models of ataxia, dystonia, and tremor. We find that recording duration circumscribes overall representations of firing rate and pattern. Notably, shorter recording durations skew estimates for global firing rate variability towards lower values. We also find that only some populations of neurons in the same mouse are more similar to each other than to neurons recorded in different mice. These data reveal that recording duration and approach are primary considerations when interpreting task-independent single-neuron firing properties. If not accounted for, group differences may be concealed or exaggerated.

Dynamic Synchronization of Purkinje Cell Simple Spikes

2006 ◽  
Vol 96 (6) ◽  
pp. 3485-3491 ◽  
Author(s):  
Soon-Lim Shin ◽  
Erik De Schutter
Keyword(s):  
Purkinje Cell ◽  
Firing Rate ◽  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Cerebellar Nuclei ◽  
Temporal Coding ◽  
Sharp Peak ◽  
Deep Cerebellar Nuclei

Purkinje cells (PCs) integrate all computations performed in the cerebellar cortex to inhibit neurons in the deep cerebellar nuclei (DCN). Simple spikes recorded in vivo from pairs of PCs separated by <100 μm are known to be synchronized with a sharp peak riding on a broad peak, but the significance of this finding is unclear. We show that the sharp peak consists exclusively of simple spikes associated with pauses in firing. The broader, less precise peak was caused by firing-rate co-modulation of faster firing spikes. About 13% of all pauses were synchronized, and these pauses had a median duration of 20 ms. As in vitro studies have reported that synchronous pauses can reliably trigger spikes in DCN neurons, we suggest that the subgroup of spikes causing the sharp peak is important for precise temporal coding in the cerebellum.

scholarly journals Non-additive activity modulation during a decision making task involving tactic selection

2021 ◽  
Author(s):  
Wilhelm Braun ◽  
Yoshiya Matsuzaka ◽  
Hajime Mushiake ◽  
Georg Northoff ◽  
André Longtin
Keyword(s):  
Decision Making ◽  
Firing Rate ◽  
Regional Differences ◽  
Single Neuron ◽  
Principal Component ◽  
Motor Area ◽  
Perceptual Decision Making ◽  
Population Activity ◽  
Time Courses

AbstractHuman brain imaging has revealed that stimulus-induced activity does generally not simply add to the pre-stimulus activity, but rather builds in a non-additive way on this activity. Here we investigate this subject at the single neuron level and address the question whether and to what extent a strong form of non-additivity where activity drops post-cue is present in different areas of monkey cortex, including prefrontal and agranular frontal areas, during a perceptual decision making task involving action and tactic selection. Specifically we analyze spike train data recorded in vivo from the posterior dorsomedial prefrontal cortex (pmPFC), the supplementary motor area (SMA) and the presupplementary motor area (pre-SMA). For each neuron, we compute the ratio of the trial-averaged pre-stimulus spike count to the trial-averaged post-stimulus count. We also perform the ratio and averaging procedures in reverse order. We find that the statistics of these quantities behave differently across areas. pmPFC involved in tactic selection shows stronger non-additivity compared to the two other areas which more generically just increase their firing rate pos-stimulus. pmPFC behaved more similarly to pre-SMA, a likely consequence of the reciprocal connections between these areas. The trial-averaged ratio statistic was reproduced by a surrogate inhomogeneous Poisson process in which the measured trial-averaged firing rate for a given neuron is used as its time-dependent rate. Principal component analysis (PCA) of the trial-averaged firing rates of neuronal ensembles further reveals area-specific time courses of response to the stimulus, including latency to peak neural response, for the typical population activity. Our work demonstrates subtle forms of area-specific non-additivity based on the fine variability structure of pre- and post-stimulus spiking activity on the single neuron level. It also reveals significant differences between areas for PCA and surrogate analysis, complementing previous observations of regional differences based solely on post-stimulus responses. Moreover, we observe regional differences in non-additivity which are related to the monkey’s successful tactic selection and decision making.

scholarly journals Effects of Glutamate andγ-Aminobutyric Acid on Spontaneously Active Intraocular Spinal Cord Graft Neurons

1991 ◽  
Vol 2 (2) ◽  
pp. 101-111
Author(s):  
J. G. Broton ◽  
R. P. Yezierski ◽  
Å. Seiger
Keyword(s):  
Spinal Cord ◽  
Firing Rate ◽  
Gaba Receptor ◽  
Aminobutyric Acid ◽  
Lumbar Spinal Cord ◽  
Adult Rat ◽  
Fetal Rat ◽  
Single Unit Recordings ◽  
Lumbar Spinal

Pieces of fetal rat lumbar spinal cord were transplanted into the anterior eye chamber of adult rat hosts. At least seven months later, extracellular single-unit recordings of spontaneously active graft neurons were made prior to and during the superfusion of either glutamate orγ-aminobutyric acid (GABA). Superfusion of glutamate produced an increase (five cells), decrease (three cells), or had no effect (two cells) on the firing rate of neurons tested. Superfusion of GABA decreased the firing rate of all twelve neurons tested, while superfusion of the GABA receptor antagonist bicuculline increased the firing rates of all eight neurons tested. The latency and magnitude of the responses to glutamate and GABA were not related to depth of the recording electrode below the graft surface. Together, these data suggest that the intraocular spinal cord graft is suitable for thein vivostudy of GABA and glutamate neuropharmacology.

scholarly journals Corticotropin-releasing factor increases Purkinje neuron excitability by modulating sodium, potassium, and Ih currents

2015 ◽  
Vol 114 (6) ◽  
pp. 3339-3350 ◽  
Author(s):  
Avraham M. Libster ◽  
Ben Title ◽  
Yosef Yarom
Keyword(s):  
Firing Rate ◽  
Stress Responses ◽  
Sodium Current ◽  
Ionic Currents ◽  
Corticotropin Releasing Factor ◽  
Voltage Dependent ◽  
Biophysical Mechanism ◽  
The Central Nervous System ◽  
Firing Properties

Corticotropin-releasing factor (CRF) is a neuromodulator closely associated with stress responses. It is synthesized and released in the central nervous system by various neurons, including neurons of the inferior olive. The targets of inferior olivary neurons, the cerebellar Purkinje neurons (PNs), are endowed with CRF receptors. CRF increases the excitability of PNs in vivo, but the biophysical mechanism is not clear. Here we examine the effect of CRF on the firing properties of PNs using acute rat cerebellar slices. CRF increased the PN firing rate, regardless of whether they were firing tonically or switching between firing and quiescent periods. Current- and voltage-clamp experiments showed that the increase in firing rate was associated with a voltage shift of the activation curve of the persistent sodium current and hyperpolarizing-activated current, as well as activation of voltage-dependent potassium current. The multiple effects on various ionic currents, which are in agreement with the possibility that activation of CRF receptors triggers several intracellular pathways, are manifested as an increase excitability of PN.

Nitroxyl Modified Tobacco Mosaic Virus as a Metal-Free High-Relaxivity MRI and EPR Active Superoxide Sensor

2018 ◽  
Author(s):  
Madushani Dharmarwardana ◽  
André F. Martins ◽  
Zhuo Chen ◽  
Philip M. Palacios ◽  
Chance M. Nowak ◽  
...  
Keyword(s):  
Tobacco Mosaic Virus ◽  
Mosaic Virus ◽  
Single Molecule ◽  
Biological Fluids ◽  
Cellular Respiration ◽  
Organic Radical ◽  
Paramagnetic Resonance ◽  
Metal Free ◽  
Disease States

Superoxide overproduction is known to occur in multiple disease states requiring critical care yet non-invasive detection of superoxide in deep tissue remains a challenge. Herein, we report a metal-free magnetic resonance imaging (MRI) and electron paramagnetic resonance (EPR) active contrast agent prepared by “click conjugating” paramagnetic organic radical contrast agents (ORCAs) to the surface of tobacco mosaic virus (TMV). While ORCAs are known to be reduced <i>in vivo</i> to an MRI/EPR silent state, their oxidation is facilitated specifically by reactive oxygen species—in particular superoxide—and are largely unaffected by peroxides and molecular oxygen. Unfortunately, single molecule ORCAs typically offer weak MRI contrast. In contrast, our data confirm that the macromolecular ORCA-TMV conjugates show marked enhancement for <i>T<sub>1</sub></i> contrast at low field (<3.0 T), and <i>T<sub>2</sub></i> contrast at high field (9.4 T). Additionally, we demonstrated that the unique topology of TMV allows for “quenchless fluorescent” bimodal probe for concurrent fluorescence and MRI/EPR imaging, which was made possible by exploiting the unique inner and outer surface of the TMV nanoparticle. <a>Finally, we show TMV-ORCAs do not respond to normal cellular respiration, minimizing the likelihood for background, yet still respond to enzymatically produced superoxide in complicated biological fluids like serum.</a>

scholarly journals A deep convolutional visual encoding model of neuronal responses in the LGN

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Eslam Mounier ◽  
Bassem Abdullah ◽  
Hani Mahdi ◽  
Seif Eldawlatly
Keyword(s):  
Firing Rate ◽  
Visual Information ◽  
Visual Stimulation ◽  
Neuronal Population ◽  
Neuronal Firing ◽  
Electrode Arrays ◽  
Deep Convolutional Neural Networks ◽  
Firing Rates ◽  
Spatiotemporal Representation

AbstractThe Lateral Geniculate Nucleus (LGN) represents one of the major processing sites along the visual pathway. Despite its crucial role in processing visual information and its utility as one target for recently developed visual prostheses, it is much less studied compared to the retina and the visual cortex. In this paper, we introduce a deep learning encoder to predict LGN neuronal firing in response to different visual stimulation patterns. The encoder comprises a deep Convolutional Neural Network (CNN) that incorporates visual stimulus spatiotemporal representation in addition to LGN neuronal firing history to predict the response of LGN neurons. Extracellular activity was recorded in vivo using multi-electrode arrays from single units in the LGN in 12 anesthetized rats with a total neuronal population of 150 units. Neural activity was recorded in response to single-pixel, checkerboard and geometrical shapes visual stimulation patterns. Extracted firing rates and the corresponding stimulation patterns were used to train the model. The performance of the model was assessed using different testing data sets and different firing rate windows. An overall mean correlation coefficient between the actual and the predicted firing rates of 0.57 and 0.7 was achieved for the 10 ms and the 50 ms firing rate windows, respectively. Results demonstrate that the model is robust to variability in the spatiotemporal properties of the recorded neurons outperforming other examined models including the state-of-the-art Generalized Linear Model (GLM). The results indicate the potential of deep convolutional neural networks as viable models of LGN firing.

scholarly journals Characterization and Reconstitution of Human Lipoyl Synthase (LIAS) Supports ISCA2 and ISCU as Primary Cluster Donors and an Ordered Mechanism of Cluster Assembly

2021 ◽  
Vol 22 (4) ◽  
pp. 1598
Author(s):  
Amber L. Hendricks ◽  
Christine Wachnowsky ◽  
Brian Fries ◽  
Insiya Fidai ◽  
James A. Cowan
Keyword(s):  
Cluster Assembly ◽  
Paramagnetic Resonance ◽  
Iron Sulfur Cluster ◽  
Sulfur Transfer ◽  
Disease States ◽  
Isolation And Characterization ◽  
Iron Sulfur ◽  
Natural Iron ◽  
Lipoyl Synthase

Lipoyl synthase (LIAS) is an iron–sulfur cluster protein and a member of the radical S-adenosylmethionine (SAM) superfamily that catalyzes the final step of lipoic acid biosynthesis. The enzyme contains two [4Fe–4S] centers (reducing and auxiliary clusters) that promote radical formation and sulfur transfer, respectively. Most information concerning LIAS and its mechanism has been determined from prokaryotic enzymes. Herein, we detail the expression, isolation, and characterization of human LIAS, its reactivity, and evaluation of natural iron–sulfur (Fe–S) cluster reconstitution mechanisms. Cluster donation by a number of possible cluster donor proteins and heterodimeric complexes has been evaluated. [2Fe–2S]-cluster-bound forms of human ISCU and ISCA2 were found capable of reconstituting human LIAS, such that complete product turnover was enabled for LIAS, as monitored via a liquid chromatography–mass spectrometry (LC–MS) assay. Electron paramagnetic resonance (EPR) studies of native LIAS and substituted derivatives that lacked the ability to bind one or the other of LIAS’s two [4Fe–4S] clusters revealed a likely order of cluster addition, with the auxiliary cluster preceding the reducing [4Fe–4S] center. These results detail the trafficking of Fe–S clusters in human cells and highlight differences with respect to bacterial LIAS analogs. Likely in vivo Fe–S cluster donors to LIAS are identified, with possible connections to human disease states, and a mechanistic ordering of [4Fe–4S] cluster reconstitution is evident.

Effect of Common Anesthetics on Dendritic Properties in Layer 5 Neocortical Pyramidal Neurons

2008 ◽  
Vol 99 (3) ◽  
pp. 1394-1407 ◽  
Author(s):  
Sarah Potez ◽  
Matthew E. Larkum
Keyword(s):  
High Frequency ◽  
Pyramidal Neurons ◽  
Animal Experiments ◽  
Apical Dendrite ◽  
Network Activity ◽  
Calcium Spikes ◽  
Firing Properties ◽  
The Impact

Understanding the impact of active dendritic properties on network activity in vivo has so far been restricted to studies in anesthetized animals. However, to date no study has been made to determine the direct effect of the anesthetics themselves on dendritic properties. Here, we investigated the effects of three types of anesthetics commonly used for animal experiments (urethane, pentobarbital and ketamine/xylazine). We investigated the generation of calcium spikes, the propagation of action potentials (APs) along the apical dendrite and the somatic firing properties in the presence of anesthetics in vitro using dual somatodendritic whole cell recordings. Calcium spikes were evoked with dendritic current injection and high-frequency trains of APs at the soma. Surprisingly, we found that the direct actions of anesthetics on calcium spikes were very different. Two anesthetics (urethane and pentobarbital) suppressed dendritic calcium spikes in vitro, whereas a mixture of ketamine and xylazine enhanced them. Propagation of spikes along the dendrite was not significantly affected by any of the anesthetics but there were various changes in somatic firing properties that were highly dependent on the anesthetic. Last, we examined the effects of anesthetics on calcium spike initiation and duration in vivo using high-frequency trains of APs generated at the cell body. We found the same anesthetic-dependent direct effects in addition to an overall reduction in dendritic excitability in anesthetized rats with all three anesthetics compared with the slice preparation.

scholarly journals High-Sugar, but Not High-Fat, Food Activates Supraoptic Nucleus Neurons in the Male Rat

Endocrinology ◽  
2017 ◽  
Vol 158 (7) ◽  
pp. 2200-2211 ◽  
Author(s):  
Catherine Hume ◽  
Nancy Sabatier ◽  
John Menzies
Keyword(s):  
Firing Rate ◽  
Supraoptic Nucleus ◽  
Male Rat ◽  
Plasma Sodium ◽  
Neural Activation ◽  
High Fat ◽  
Gastric Distention ◽  
High Sugar ◽  
Anesthetized Rats

Abstract Oxytocin is a potent anorexigen and is believed to have a role in satiety signaling. We developed rat models to study the activity of oxytocin neurons in response to voluntary consumption or oral gavage of foods using c-Fos immunohistochemistry and in vivo electrophysiology. Using c-Fos expression as an indirect marker of neural activation, we showed that the percentage of magnocellular oxytocin neurons expressing c-Fos increased with voluntary consumption of sweetened condensed milk (SCM). To model the effect of food in the stomach, we gavaged anesthetized rats with SCM. The percentage of supraoptic nucleus and paraventricular nucleus magnocellular oxytocin-immunoreactive neurons expressing c-Fos increased with SCM gavage but not with gastric distention. To further examine the activity of the supraoptic nucleus, we made in vivo electrophysiological recordings from SON neurons, where anesthetized rats were gavaged with SCM or single cream. Pharmacologically identified oxytocin neurons responded to SCM gavage with a linear, proportional, and sustained increase in firing rate, but cream gavage resulted in a transient reduction in firing rate. Blood glucose increased after SCM gavage but not cream gavage. Plasma osmolarity and plasma sodium were unchanged throughout. We show that in response to high-sugar, but not high-fat, food in the stomach, there is an increase in the activity of oxytocin neurons. This does not appear to be a consequence of stomach distention or changes in osmotic pressure. Our data suggest that the presence of specific foods with different macronutrient profiles in the stomach differentially regulates the activity of oxytocin neurons.

scholarly journals The Whisking Rhythm Generator: A Novel Mammalian Network for the Generation of Movement

2007 ◽  
Vol 97 (3) ◽  
pp. 2148-2158 ◽  
Author(s):  
Nathan P. Cramer ◽  
Ying Li ◽  
Asaf Keller
Keyword(s):  
Firing Rate ◽  
Serotonin Receptor ◽  
Central Pattern Generators ◽  
Rhythm Generator ◽  
Low Concentrations ◽  
Rhythmic Firing ◽  
Pattern Generators ◽  
Cortical Inputs

Using the rat vibrissa system, we provide evidence for a novel mechanism for the generation of movement. Like other central pattern generators (CPGs) that underlie many movements, the rhythm generator for whisking can operate without cortical inputs or sensory feedback. However, unlike conventional mammalian CPGs, vibrissa motoneurons (vMNs) actively participate in the rhythmogenesis by converting tonic serotonergic inputs into the patterned motor output responsible for movement of the vibrissae. We find that, in vitro, a serotonin receptor agonist, α-Me-5HT, facilitates a persistent inward current (PIC) and evokes rhythmic firing in vMNs. Within each motoneuron, increasing the concentration of α-Me-5HT significantly increases the both the magnitude of the PIC and the motoneuron's firing rate. Riluzole, which selectively suppresses the Na+ component of PICs at low concentrations, causes a reduction in both of these phenomena. The magnitude of this reduction is directly correlated with the concentration of riluzole. The joint effects of riluzole on PIC magnitude and firing rate in vMNs suggest that the two are causally related. In vivo we find that the tonic activity of putative serotonergic premotoneurons is positively correlated with the frequency of whisking evoked by cortical stimulation. Taken together, these results support the hypothesized novel mammalian mechanism for movement generation in the vibrissa motor system where vMNs actively participate in the rhythmogenesis in response to tonic drive from serotonergic premotoneurons.

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