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Gregory D Horwitz

Publications and source records attributed to Gregory D Horwitz.

8 recordsLinked to original sources
PubMed2021

Comparative cellular analysis of motor cortex in human, marmoset and mouse.

The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch-seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.

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PubMed2006

Selective and quickly reversible inactivation of mammalian neurons in vivo using the Drosophila allatostatin receptor.

Genetic strategies for perturbing activity of selected neurons hold great promise for understanding circuitry and behavior. Several such strategies exist, but there has been no direct demonstration of reversible inactivation of mammalian neurons in vivo. We previously reported quickly reversible inactivation of neurons in vitro using expression of the Drosophila allatostatin receptor (AlstR). Here, adeno-associated viral vectors are used to express AlstR in vivo in cortical and thalamic neurons of rats, ferrets, and monkeys. Application of the receptor's ligand, allatostatin (AL), leads to a dramatic reduction in neural activity, including responses of visual neurons to optimized visual stimuli. Additionally, AL eliminates activity in spinal cords of transgenic mice conditionally expressing AlstR. This reduction occurs selectively in AlstR-expressing neurons. Inactivation can be reversed within minutes upon washout of the ligand and is repeatable, demonstrating that the AlstR/AL system is effective for selective, quick, and reversible silencing of mammalian neurons in vivo.

Action Potentials↗
PubMed2005

Paucity of chromatic linear motion detectors in macaque V1.

The motion of a color-defined edge is often more difficult to perceive than the motion of a luminance-defined edge. Neurons subserving motion vision may therefore be particularly sensitive to luminance contrast. One class of neurons thought to play a critical role in motion perception is V1 neurons whose spatiotemporal receptive fields are oriented in space-time. We used the reverse correlation technique to study the relationship between color tuning and space-time receptive field orientation in V1 neurons of awake, fixating monkeys. Neurons with space-time oriented receptive fields were tuned almost exclusively for luminance, whereas neurons with nonoriented space-time receptive fields were tuned for luminance or for color. These results suggest that the special role of luminance contrast in motion perception is due in part to the establishment of space-time oriented receptive fields among luminance-tuned, but not color-tuned, V1 neurons.

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PubMed2004

Blue-yellow signals are enhanced by spatiotemporal luminance contrast in macaque V1.

We measured the color tuning of a population of S-cone-driven V1 neurons in awake, fixating monkeys. Analysis of randomly chosen color stimuli that were effective in evoking action potentials showed that these neurons received opposite sign input from the S cones and a combination of L and M cones. Surprisingly, these cells also responded to LM cone contrast irrespective of polarity, a nonlinear sensitivity that was masked by conventional linear analysis methods. Taken together, these observations can be summarized in a nonlinear model that combines nonopponent and opponent signals such that luminance contrast enhances color processing. These findings indicate that important aspects of the cortical representation of color cannot be described by classical linear analysis, and reveal a possible neural correlate of perceptual color-luminance interactions.

Action Potentials↗
PubMed2004

Direction-selective visual responses in macaque superior colliculus induced by behavioral training.

In a previous report, we described a heretofore undetected population of neurons in the intermediate and deep layers of the monkey superior colliculus (SC) that yielded directionally selective visual responses to stimuli presented within the central 4 degrees of the visual field. We observed these neurons in three monkeys that had been extensively trained to perform a visual direction discrimination task in this region of the visual field. The task required the monkeys to report the perceived direction of motion by making a saccadic eye movement to one of two targets aligned with the two possible directions of motion. We hypothesized that these neurons reflect a learned association between visual motion direction and saccade direction formed through extensive training on the direction discrimination task. We tested this hypothesis by searching for direction-selective visual responses in two monkeys that had been trained to perform a similar motion discrimination task in which the direction of stimulus motion was dissociated from the direction of the operant saccade. Strongly directional visual responses were absent in these monkeys, consistent with the notion that extensive training can induce highly specific visual responses in a subpopulation of SC neurons.

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PubMed2004

Representation of an abstract perceptual decision in macaque superior colliculus.

We recorded from neurons in the intermediate and deep layers of the superior colliculus (SC) while monkeys performed a novel direction discrimination task. In contrast to the task we used previously, the new version required the monkey to dissociate perceptual judgments from preparation to execute specific operant saccades. The monkey discriminated between 2 opposed directions of motion in a random-dot motion stimulus and was required to maintain the decision in memory throughout a delay period before the target of the required operant saccade was revealed. We hypothesized that perceptual decisions made in this paradigm would be represented in an "abstract" or "categorical" form within the brain, probably in the frontal cortex, and that decision-related neural activity would be eliminated from spatially organized preoculomotor structures such as the SC. To our surprise, however, a small population of neurons in the intermediate and deep layers of the SC fired in a choice-specific manner early in the trial well before the monkey could plan the operant saccade. Furthermore, the representation of the decision during the delay period appeared to be spatial: the active region in the SC map corresponded to the region of space toward which the perceptually discriminated stimulus motion flowed. Electrical microstimulation experiments suggested that these decision-related SC signals were not merely related to covert saccade planning. We conclude that monkeys may employ, in part, a spatially referenced mnemonic strategy for representing perceptual decisions, even when an abstract, categorical representation might appear more likely a priori.

Algorithms↗
PubMed2003

Short-latency fixational saccades induced by luminance increments.

We investigated the effect of peripheral visual stimulation on small-amplitude saccades that occur naturally during fixation. Two macaque monkeys were rewarded for fixating while a colorful stimulus flickered randomly in the periphery. Reverse correlation revealed a lawful relationship between the stimulus sequence and saccade occurrences: on average, a transient increase in stimulus intensity evoked saccades at a latency of approximately 70 ms. The spectral tuning of this increase was roughly, but not exactly, consistent with a pure luminance increase. We conclude that peripheral luminance increases can evoke fixational saccades.

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