@article {126, title = {REST Regulates Non-Cell-Autonomous Neuronal Differentiation and Maturation of Neural Progenitor Cells via Secretogranin II.}, journal = {J Neurosci}, volume = {35}, year = {2015}, month = {2015 Nov 4}, pages = {14872-84}, abstract = {

UNLABELLED: RE-1 silencing transcription factor (REST), a master negative regulator of neuronal differentiation, controls neurogenesis by preventing the differentiation of neural stem cells. Here we focused on the role of REST in the early steps of differentiation and maturation of adult hippocampal progenitors (AHPs). REST knockdown promoted differentiation and affected the maturation of rat AHPs. Surprisingly, REST knockdown cells enhanced the differentiation of neighboring wild-type AHPs, suggesting that REST may play a non-cell-autonomous role. Gene expression analysis identified Secretogranin II (Scg2) as the major secreted REST target responsible for the non-cell-autonomous phenotype. Loss-of-function of Scg2 inhibited differentiation in vitro, and exogenous SCG2 partially rescued this phenotype. Knockdown of REST in neural progenitors in mice led to precocious maturation into neurons at the expense of mushroom spines in vivo. In summary, we found that, in addition to its cell-autonomous function, REST regulates differentiation and maturation of AHPs non-cell-autonomously via SCG2.

SIGNIFICANCE STATEMENT: Our results reveal that REST regulates differentiation and maturation of neural progenitor cells in vitro by orchestrating both cell-intrinsic and non-cell-autonomous factors and that Scg2 is a major secretory target of REST with a differentiation-enhancing activity in a paracrine manner. In vivo, REST depletion causes accelerated differentiation of newborn neurons at the expense of spine defects, suggesting a potential role for REST in the timing of the maturation of granule neurons.

}, keywords = {Animals, Cell Differentiation, Cells, Cultured, Female, Hippocampus, Mice, Mice, Inbred C57BL, Neural Stem Cells, Neurogenesis, Neurons, Rats, Wistar, Repressor Proteins, Secretogranin II}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.4286-14.2015}, author = {Kim, Hyung Joon and Denli, Ahmet M and Wright, Rebecca and Baul, Tithi D and Clemenson, Gregory D and Morcos, Ari S and Zhao, Chunmei and Schafer, Simon T and Gage, Fred H and Kagalwala, Mohamedi N} } @article {1671, title = {Rats and humans differ in processing collinear visual features.}, journal = {Front Neural Circuits}, volume = {7}, year = {2013}, month = {2013}, pages = {197}, abstract = {

Behavioral studies in humans and rats demonstrate that visual detection of a target stimulus is sensitive to surrounding spatial patterns. In both species, the detection of an oriented visual target is affected when the surrounding region contains flanking stimuli that are collinear to the target. In many studies, collinear flankers have been shown to improve performance in humans, both absolutely (compared to performance with no flankers) and relative to non-collinear flankers. More recently, collinear flankers have been shown to impair performance in rats both absolutely and relative to non-collinear flankers. However, these observations spanned different experimental paradigms. Past studies in humans have shown that the magnitude and even sign of flanker effects can depend critically on the details of stimulus and task design. Therefore either task differences or species could explain the opposite findings. Here we provide a direct comparison of behavioral data between species and show that these differences persist--collinear flankers improve performance in humans, and impair performance in rats--in spite of controls that match stimuli, experimental paradigm, and learning procedure. There is evidence that the contrasts of the target and the flankers could affect whether surround processing is suppressive or facilitatory. In a second experiment, we explored a range of contrast conditions in the rat, to determine if contrast could explain the lack of collinear facilitation. Using different pairs of target and flanker contrast, the rat{\textquoteright}s collinear impairment was confirmed to be robust across a range of contrast conditions. We conclude that processing of collinear features is indeed different between rats and humans. We speculate that the observed difference between rat and human is caused by the combined impact of differences in the statistics in natural retinal images, the representational capacity of neurons in visual cortex, and attention.

}, keywords = {Animals, Attention, Contrast Sensitivity, Humans, Orientation, Pattern Recognition, Visual, Photic Stimulation, Rats, Visual Cortex, Visual Perception}, issn = {1662-5110}, doi = {10.3389/fncir.2013.00197}, author = {Meier, Philip M and Reinagel, Pamela} } @article {195, title = {Rat performance on visual detection task modeled with divisive normalization and adaptive decision thresholds.}, journal = {J Vis}, volume = {11}, year = {2011}, month = {2011}, abstract = {

Performance on any perceptual task depends on both the perceptual capacity and the decision strategy of the subject. We provide a model to fit both aspects and apply it to data from rats performing a detection task. When rats must detect a faint visual target, the presence of other nearby stimuli ("flankers") increases the difficulty of the task. In this study, we consider two specific factors. First, flankers could diminish the sensory response to the target via spatial contrast normalization in early visual processing. Second, rats may treat the sensory signal caused by the flankers as if it belonged to the target. We call this source confusion, which may be sensory, cognitive, or both. We account for contrast normalization and source confusion by fitting model parameters to the likelihood of the observed behavioral data. We test multiple combinations of target and flanker contrasts using a yes/no detection task. Contrast normalization was crucial to explain the rats{\textquoteright} flanker-induced detection impairment. By adding a decision variable to the contrast normalization framework, our model provides a new tool to assess differences in visual or cognitive brain function between normal and abnormal rodents.

}, keywords = {Adaptation, Physiological, Animals, Choice Behavior, Cognition, Conditioning (Psychology), Contrast Sensitivity, Male, Models, Neurological, Photic Stimulation, Psychomotor Performance, Rats, Rats, Long-Evans, Visual Perception}, issn = {1534-7362}, doi = {10.1167/11.9.1}, author = {Meier, Philip and Reinagel, Pamela} }