Biology subjects

Tyssowski, K. M.

Publications and source records attributed to Tyssowski, K. M..

3 recordsLinked to original sources

bioRxiv2025

Evolutionary expansion of the corticospinal system is linked to dexterity in Peromyscus mice

While the central nervous system is perpetually reshaped by evolution, the principles governing how such changes promote ecologically relevant behaviors without breaking established functions are poorly understood. The expansion of neuron number is a potential mechanism by which the nervous system evolves to support changes in behavior without disrupting existing circuit function. Corticospinal neurons (CSNs) are a classic example: an expansion in the corticospinal system in the primate lineage has been hypothesized to underlie their exceptional dexterity. However, the role of CSN number in behavior has been difficult to assess due to the lack of a tractable model system. We compared two closely related subspecies of deer mice (Peromyscus maniculatus): forest mice, which evolved the ability to adeptly climb, presumably to support a semi-arboreal lifestyle, and prairie mice, which are less proficient climbers. We find that forest mice have about two-fold larger corticospinal tracts (CSTs) driven by an increase in CSN number in secondary motor and sensory cortical areas (M2 and S2). Furthermore, forest mice display greater manual dexterity than their prairie counterparts in a reach-to-grasp task, consistent with the idea that an increase in CSN number supports more dexterous behavior. High-throughput neural recordings during this task revealed a difference in the timing of neural activity between forest and prairie mice, specifically in M2: in forest mice, the peak of activity was shifted towards the grasping phase of the behavior. Forest mice also outperform their prairie counterparts on an ecologically relevant climbing task, where they spend more time upright crossing a thin rod, move faster, and right themselves more quickly when they fall, suggesting a general difference in motor dexterity not restricted to hand use. Finally, we use F2 hybrid animals to show that CST size is correlated with climbing dexterity, providing support for the long-standing hypothesis that corticospinal system expansion supports the evolution of dexterity. Together, our work establishes the forest-prairie deer mouse system as a model to investigate the role of neuron number expansion, and CSNs in particular, in dexterous movement.

neuroscience↗

bioRxiv2019

Blue light induces neuronal-activity-regulated gene expression in the absence of optogenetic proteins

Optogenetics is widely used to control diverse cellular functions with light, requiring experimenters to expose cells to bright light. Because extended exposure to visible light can be toxic to cells, it is important to characterize the effects of light stimulation on cellular function in the absence of exogenous optogenetic proteins. Here we exposed cultured mouse cortical neurons that did not express optogenetic proteins to several hours of flashing blue, red, or green light. We found that exposing neurons to as short as one hour of blue, but not red or green, light results in the induction of neuronal-activity-regulated genes without inducing neuronal activity. Our findings suggest blue light stimulation is ill-suited to long-term optogenetic experiments, especially those that measure transcription.\n\nSignificance StatementOptogenetics is widely used to control cellular functions using light. In neuroscience, channelrhodopsins, exogenous light-sensitive channels, are used to achieve light-dependent control of neuronal firing. This optogenetic control of neuronal firing requires exposing neurons to high-powered light. We ask how this light exposure, in the absence of channelrhodopsin, affects the expression of neuronal-activity-regulated genes, i.e., the genes that are transcribed in response to neuronal stimuli. Surprisingly, we find that neurons without channelrhodopsin express neuronal-activity-regulated genes in response to as short as an hour of blue, but not red or green, light exposure. These findings suggest that experimenters wishing to achieve longer-term (an hour or more) optogenetic control over neuronal firing should avoid using systems that require blue light.

neuroscience↗

bioRxiv2017

Distinct neuronal activity patterns induce different gene expression programs

Brief and sustained neuronal activity patterns can have opposite effects on synaptic strength that both require activity-regulated gene (ARG) expression. However, whether distinct patterns of activity induce different sets of ARGs is unknown. In genome-scale experiments, we reveal that a neurons activity-pattern history can be predicted from the ARGs it expresses. Surprisingly, brief activity selectively induces a small subset of the ARG program that that corresponds precisely to the first of three temporal waves of genes induced by sustained activity. These first-wave genes are distinguished by an open chromatin state, proximity to rapidly activated enhancers, and a requirement for MAPK/ERK signaling for their induction. MAPK/ERK mediates rapid RNA polymerase recruitment to promoters, as well as enhancer RNA induction but not histone acetylation at enhancers. Thus, the same mechanisms that establish the multi-wave temporal structure of ARG induction also enable different sets of genes to be induced by distinct activity patterns.

neuroscience↗