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Gabriel Kreiman

Publications and source records attributed to Gabriel Kreiman.

10 recordsLinked to original sources
PubMed2006

Gene expression changes and molecular pathways mediating activity-dependent plasticity in visual cortex.

Two key models for examining activity-dependent development of primary visual cortex (V1) involve either reduction of activity in both eyes via dark-rearing (DR) or imbalance of activity between the two eyes via monocular deprivation (MD). Combining DNA microarray analysis with computational approaches, RT-PCR, immunohistochemistry and physiological imaging, we find that DR leads to (i) upregulation of genes subserving synaptic transmission and electrical activity, consistent with a coordinated response of cortical neurons to reduction of visual drive, and (ii) downregulation of parvalbumin expression, implicating parvalbumin-expressing interneurons as underlying the delay in cortical maturation after DR. MD partially activates homeostatic mechanisms but differentially upregulates molecular pathways related to growth factors and neuronal degeneration, consistent with reorganization of connections after MD. Expression of a binding protein of insulin-like growth factor-1 (IGF1) is highly upregulated after MD, and exogenous application of IGF1 prevents the physiological effects of MD on ocular dominance plasticity examined in vivo.

Animals↗
PubMed2006

Object selectivity of local field potentials and spikes in the macaque inferior temporal cortex.

Local field potentials (LFPs) arise largely from dendritic activity over large brain regions and thus provide a measure of the input to and local processing within an area. We characterized LFPs and their relationship to spikes (multi and single unit) in monkey inferior temporal cortex (IT). LFP responses in IT to complex objects showed strong selectivity at 44% of the sites and tolerance to retinal position and size. The LFP preferences were poorly predicted by the spike preferences at the same site but were better explained by averaging spikes within approximately 3 mm. A comparison of separate sites suggests that selectivity is similar on a scale of approximately 800 microm for spikes and approximately 5 mm for LFPs. These observations imply that inputs to IT neurons convey selectivity for complex shapes and that such input may have an underlying organization spanning several millimeters.

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PubMed2005

Fast readout of object identity from macaque inferior temporal cortex.

Understanding the brain computations leading to object recognition requires quantitative characterization of the information represented in inferior temporal (IT) cortex. We used a biologically plausible, classifier-based readout technique to investigate the neural coding of selectivity and invariance at the IT population level. The activity of small neuronal populations (approximately 100 randomly selected cells) over very short time intervals (as small as 12.5 milliseconds) contained unexpectedly accurate and robust information about both object "identity" and "category." This information generalized over a range of object positions and scales, even for novel objects. Coarse information about position and scale could also be read out from the same population.

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PubMed2004

Variation in alternative splicing across human tissues.

BACKGROUND: Alternative pre-mRNA splicing (AS) is widely used by higher eukaryotes to generate different protein isoforms in specific cell or tissue types. To compare AS events across human tissues, we analyzed the splicing patterns of genomically aligned expressed sequence tags (ESTs) derived from libraries of cDNAs from different tissues. RESULTS: Controlling for differences in EST coverage among tissues, we found that the brain and testis had the highest levels of exon skipping. The most pronounced differences between tissues were seen for the frequencies of alternative 3' splice site and alternative 5' splice site usage, which were about 50 to 100% higher in the liver than in any other human tissue studied. Quantifying differences in splice junction usage, the brain, pancreas, liver and the peripheral nervous system had the most distinctive patterns of AS. Analysis of available microarray expression data showed that the liver had the most divergent pattern of expression of serine-arginine protein and heterogeneous ribonucleoprotein genes compared to the other human tissues studied, possibly contributing to the unusually high frequency of alternative splice site usage seen in liver. Sequence motifs enriched in alternative exons in genes expressed in the brain, testis and liver suggest specific splicing factors that may be important in AS regulation in these tissues. CONCLUSIONS: This study distinguishes the human brain, testis and liver as having unusually high levels of AS, highlights differences in the types of AS occurring commonly in different tissues, and identifies candidate cis-regulatory elements and trans-acting factors likely to have important roles in tissue-specific AS in human cells.

Alternative Splicing↗
PubMed2004

Identification of sparsely distributed clusters of cis-regulatory elements in sets of co-expressed genes.

Sequence information and high-throughput methods to measure gene expression levels open the door to explore transcriptional regulation using computational tools. Combinatorial regulation and sparseness of regulatory elements throughout the genome allow organisms to control the spatial and temporal patterns of gene expression. Here we study the organization of cis-regulatory elements in sets of co-regulated genes. We build an algorithm to search for combinations of transcription factor binding sites that are enriched in a set of potentially co-regulated genes with respect to the whole genome. No knowledge is assumed about involvement of specific sets of transcription factors. Instead, the search is exhaustively conducted over combinations of up to four binding sites obtained from databases or motif search algorithms. We evaluate the performance on random sets of genes as a negative control and on three biologically validated sets of co-regulated genes in yeasts, flies and humans. We show that we can detect DNA regions that play a role in the control of transcription. These results shed light on the structure of transcription regulatory regions in eukaryotes and can be directly applied to clusters of co-expressed genes obtained in gene expression studies. Supplementary information is available at http://www.mit.edu/ approximately kreiman/resources/cisregul/.

Algorithms↗
PubMed2004

A gene atlas of the mouse and human protein-encoding transcriptomes.

The tissue-specific pattern of mRNA expression can indicate important clues about gene function. High-density oligonucleotide arrays offer the opportunity to examine patterns of gene expression on a genome scale. Toward this end, we have designed custom arrays that interrogate the expression of the vast majority of protein-encoding human and mouse genes and have used them to profile a panel of 79 human and 61 mouse tissues. The resulting data set provides the expression patterns for thousands of predicted genes, as well as known and poorly characterized genes, from mice and humans. We have explored this data set for global trends in gene expression, evaluated commonly used lines of evidence in gene prediction methodologies, and investigated patterns indicative of chromosomal organization of transcription. We describe hundreds of regions of correlated transcription and show that some are subject to both tissue and parental allele-specific expression, suggesting a link between spatial expression and imprinting.

Animals↗
PubMed2004

Consciousness and neurosurgery.

The neuronal basis of consciousness is the greatest challenge to the scientific worldview. Much relevant empirical work is carried out on the minimal neuronal mechanisms underlying any one specific conscious percept. Two broad approaches are popular among brain scientists: electrophysiological recordings from individual neurons in the cortex of behaving monkeys or behavior combined with functional brain imaging in humans. However, many aspects of consciousness are problematic or remain off-limits to the former approach, while the latter one lacks sufficient spatial and temporal resolution to monitor individual neurons that are key to perception, thought, memory, and action. It is here that neurosurgeons, probing the living human brain on a daily basis, can play a decisive role. This article explores the contributions of neurosurgeons to this quest and outlines some of the results that have already been achieved.

Animals↗
PubMed2002

Single-neuron correlates of subjective vision in the human medial temporal lobe.

Visual information from the environment is transformed into perceptual sensations through several stages of neuronal processing. Flash suppression constitutes a striking example in which the same retinal input can give rise to two different conscious visual percepts. We directly recorded the responses of individual neurons during flash suppression in the human amygdala, entorhinal cortex, hippocampus, and parahippocampal gyrus, allowing us to explore the neuronal responses in untrained subjects at a high spatial and temporal resolution in the medial temporal lobe. Subjects were patients with pharmacologically intractable epilepsy implanted with depth electrodes to localize the seizure onset focus. We observed that the activity of two thirds of all visually selective neurons followed the perceptual alternations rather than the retinal input. None of the selective neurons responded to a perceptually suppressed stimulus. Therefore, the activity of most individual neurons in the medial temporal lobe of naive human subjects directly correlates with the phenomenal visual experience.

Adult↗
PubMed2002

Stimulus encoding and feature extraction by multiple sensory neurons.

Neighboring cells in topographical sensory maps may transmit similar information to the next higher level of processing. How information transmission by groups of nearby neurons compares with the performance of single cells is a very important question for understanding the functioning of the nervous system. To tackle this problem, we quantified stimulus-encoding and feature extraction performance by pairs of simultaneously recorded electrosensory pyramidal cells in the hindbrain of weakly electric fish. These cells constitute the output neurons of the first central nervous stage of electrosensory processing. Using random amplitude modulations (RAMs) of a mimic of the fish's own electric field within behaviorally relevant frequency bands, we found that pyramidal cells with overlapping receptive fields exhibit strong stimulus-induced correlations. To quantify the encoding of the RAM time course, we estimated the stimuli from simultaneously recorded spike trains and found significant improvements over single spike trains. The quality of stimulus reconstruction, however, was still inferior to the one measured for single primary sensory afferents. In an analysis of feature extraction, we found that spikes of pyramidal cell pairs coinciding within a time window of a few milliseconds performed significantly better at detecting upstrokes and downstrokes of the stimulus compared with isolated spikes and even spike bursts of single cells. Coincident spikes can thus be considered "distributed bursts." Our results suggest that stimulus encoding by primary sensory afferents is transformed into feature extraction at the next processing stage. There, stimulus-induced coincident activity can improve the extraction of behaviorally relevant features from the stimulus.

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