Biomedical subjects

Yoram Ben-Shaul

Publications and source records attributed to Yoram Ben-Shaul.

7 recordsLinked to original sources

PubMed2006

Temporally precise cortical firing patterns are associated with distinct action segments.

Despite many reports indicating the existence of precise firing sequences in cortical activity, serious objections have been raised regarding the statistics used to detect them and the relations of these sequences to behavior. We show that in behaving monkeys, pairs of spikes from different neurons tend to prefer certain time delays when measured in relation to a specific behavior. Single-unit activity was recorded from eight microelectrodes inserted into the motor and premotor cortices of two monkeys while they were performing continuous drawinglike hand movements. Repeated scribbling paths, termed drawing components, were extracted by data-mining techniques. The set of the least predictable relations between drawing components and pairs of neurons was determined and represented by one statistic termed the relations score. The chance probability of the relations score was evaluated by teetering the spike times: 1,000 surrogates were generated by randomly teetering the original time of each spike in a small window. In nine of 13 experimental days the precision was better than 12 ms and, in the best case, spike precision reached 0.5 ms.

Animals↗

PubMed2006

Modulated splicing-associated gene expression in P19 cells expressing distinct acetylcholinesterase splice variants.

Alternative splicing configurations and acetylcholinesterase (AChE) gene expression are both modified in neurons under stress. However, it is unclear if these phenomena are functionally interrelated. Using a home-made spotted microarray focused on splicing-associated transcripts, we tested the effects of excess 3' splice variants of human AChE on splicing-related gene expression in semi-differentiated neuronal P19 cells. Of the tested transcripts, 17.3% and 20.2% showed modified expression levels (log2 of the ratio<-0.3 or>0.3) in transfected P19 cells overexpressing the stress-inducible AChE-R variant or the synaptic AChE-S protein, respectively. Multiple transcripts encoding serine-arginine rich (SR) and SR-related splicing regulators were suppressed in cells expressing either of these variants, whereas the gene groups including splicing-related helicases and transcripts involved in apoptosis displayed variant-specific changes. Our findings are compatible with the assumption that both neuronal overexpression and alternative splicing of pre-AChE mRNA may be causally involved in initiating global changes in neuronal alternative splicing, causing subsequent modifications in the expression patterns of numerous target genes.

Acetylcholinesterase↗

PubMed2005

Neurons of the cerebral cortex exhibit precise interspike timing in correspondence to behavior.

We show that times of spikes can be very precise. In the cerebral cortex, where each nerve cell is affected by thousands of others, it is the common belief that the exact time of a spike is random up to an averaged firing rate over tens of milliseconds. In a brain slice, precise time relations of several neurons have been observed. It remained unclear whether this phenomenon can also be observed in brains of behaving animals. Here we show, in behaving monkeys, that time intervals between spikes, measured in correspondence to a specific behavior, may be controlled to within the milliseconds range.

Action Potentials↗

PubMed2005

Chronic cholinergic imbalances promote brain diffusion and transport abnormalities.

Cholinergic imbalances occur after traumatic effects and in the initial stages of neurodegenerative diseases, but their long-lasting effects remained largely unexplained. To address this, we used TgS transgenic mice constitutively overexpressing synaptic acetylcholinesterase (AChE-S) and presenting a complex phenotype of progressive neurodeterioration. T1- and T2-weighted magnetic resonance (MR) brain images appeared similar. However, diffusion-weighted MRI showed decreased baseline water apparent diffusion coefficient in the brains of TgS animals. Furthermore, contrast-enhanced MRI after gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) injection demonstrated slower recovery of normal signals in the TgS brains than with controls. Perfusion MR imaging and difference T1 maps calculated from pre- postcontrast T1-weighted MR images indicated accumulation of more Gd-DTPA molecules in the TgS brains than in the parent strain, reflecting impaired blood-brain barrier (BBB) functioning in these transgenic mice. To explore the molecular mechanism(s) underlying these global phenotypes, we performed microarray analysis in the stress-controlling prefrontal cortex of TgS vs. strain-matched wild-type animals. Profound overexpression of numerous ion channels, transporters, and adhesion genes was confirmed by real time RT-PCR tests. Immunohistochemical and immunoblot analyses revealed corresponding increases in the level and cellular distributions of the chloride channel CLCN3 and the water channel AQP4, both of which contribute to BBB maintenance. Our study attributes to balanced cholinergic neurotransmission, a central role in the brain's maintenance of water diffusion and ion transport, and indicates that chronic impairments in this maintenance facilitate neurodeterioration through interference with BBB function.

Acetylcholine↗

PubMed2004

Identifying subtle interrelated changes in functional gene categories using continuous measures of gene expression.

MOTIVATION: Analysis of large-scale expression data is greatly facilitated by the availability of gene ontologies (GOs). Many current methods test whether sets of transcripts annotated with specific ontology terms contain an excess of 'changed' transcripts. This approach suffers from two main limitations. First, since gene expression is continuous rather than discrete, designating a gene as changed or unchanged is arbitrary and oblivious to the actual magnitude of the change. Second, by considering only the number of changed genes, finer changes in expression patterns associated with the category may be ignored. Since genes generally participate in multiple networks, widespread and subtle modifications in expression patterns are at least as important as extreme increases/decreases of a few genes. RESULTS: Numerical simulations confirm that incorporating continuous measures of gene expression for all measured transcripts yields detection of considerably more subtle changes. Applying continuous measures to microarray data from brains of mice injected with the Parkinsonian neurotoxin, MPTP, enables detection of changes in various biologically relevant GO terms, many of which are overlooked by discrete approaches.

Algorithms↗

PubMed2003

Neuronal activity in motor cortical areas reflects the sequential context of movement.

Natural actions can be described as chains of simple elements, whereas individual motion elements are readily concatenated to generate countless movement sequences. Sequence-specific neurons have been described extensively, suggesting that the motor system may implement temporally complex motions by using such neurons to recruit lower-level movement neurons modularly. Here, we set out to investigate whether activity of movement-related neurons is independent of the sequential context of the motion. Two monkeys were trained to perform linear arm movements either individually or as components of double-segment motions. However, comparison of neuronal activity between these conditions is delicate because subtle kinematic variations generally occur within different contexts. We therefore used extensive procedures to identify the contribution of variations in motor execution to differences in neuronal activity. Yet, even after application of these procedures we find that neuronal activity in the motor cortex (PMd and M1) associated with a given motion segment differs between the two contexts. These differences appear during preparation and become even more prominent during motion execution. Interestingly, despite context-related differences on the single-neuron level, the population as a whole still allows a reliable readout of movement direction regardless of the sequential context. Thus the direction of a movement and the sequential context in which it is embedded may be simultaneously and reliably encoded by neurons in the motor cortex.

Action Potentials↗

PubMed2003

Dynamical organization of directional tuning in the primate premotor and primary motor cortex.

Although previous studies have shown that activity of neurons in the motor cortex is related to various movement parameters, including the direction of movement, the spatial pattern by which these parameters are represented is still unresolved. The current work was designed to study the pattern of representation of the preferred direction (PD) of hand movement over the cortical surface. By studying pairwise PD differences, and by applying a novel implementation of the circular variance during preparation and movement periods in the context of a center-out task, we demonstrate a nonrandom distribution of PDs over the premotor and motor cortical surface of two monkeys. Our analysis shows that, whereas PDs of units recorded by nonadjacent electrodes are not more similar than expected by chance, PDs of units recorded by adjacent electrodes are. PDs of units recorded by a single electrode display the greatest similarity. Comparison of PD distributions during preparation and movement reveals that PDs of nearby units tend to be more similar during the preparation period. However, even for pairs of units recorded by a single electrode, the mean PD difference is typically large (45 degrees and 75 degrees during preparation and movement, respectively), so that a strictly modular representation of hand movement direction over the cortical surface is not supported by our data.

Animals↗