Experience-dependent specialization of receptive field surround for selective coding of natural scenes

At eye opening, neurons in primary visual cortex (V1) are selective for stimulus features, but circuits continue to refine in an experience-dependent manner for some weeks thereafter. How these changes contribute to the coding of visual features embedded in complex natural scenes remains unknown. Here we show that normal visual experience after eye opening is required for V1 neurons to develop a sensitivity for the statistical structure of natural stimuli extending beyond the boundaries of their receptive fields (RFs), which leads to improvements in coding efficiency for full-field natural scenes (increased selectivity and information rate). These improvements are mediated by an experience-dependent increase in the effectiveness of natural surround stimuli to hyperpolarize the membrane potential specifically during RF-stimulus epochs triggering action potentials. We suggest that neural circuits underlying surround modulation are shaped by the statistical structure of visual input, which leads to more selective coding of features in natural scenes

The cognitive profile of type 1 Gaucher disease patients

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: The absence of neurological symptoms and signs is traditionally considered mandatory for a diagnosis of type 1 Gaucher disease (GD1), but in recent years many reports have emerged on neurological manifestations in GD1 patients. Nevertheless, it has been unclear whether cognitive deficits are part of the disease as well. METHODS: Cognitive function was assessed in a large cohort of GD1 patients with the use of the CDR system, a set of computerised cognitive tests. Testing was performed at baseline and every 6 months thereafter during a two-year study period. RESULTS: Our patient cohort (84 patients, median age 40 years, median time from diagnosis 15 years) showed mild deficits relative to healthy age-matched subjects on the composite scores: power of attention (Z-score (mean ± SD) -0.9 ± 1.37) and speed of memory (Z-score (mean ± SD) -1.39 ± 1.49). No decline in cognitive function was seen during the two-year period. Age correlated with the composite scores variability of attention and quality of working memory. Moreover, severely affected patients (Zimran severity score (SSI) ≥ 15) scored more poorly compared to mildly affected patients (SSI ≤ 5) on the composite measure power of attention, reflecting the ability to concentrate. CONCLUSIONS: GD1 patients exhibit mild deficits in power of attention and speed of memory, reflecting a decreased ability to focus attention and process information, together with a slowing in the speed of retrieval of items from memory. The clinical relevance of these findings is uncertain.This work was supported by Actelion Pharmaceuticals Ltd, Allschwil, Switzerland. This study was set up under the auspices of the European Working Group on Gaucher Disease (EWGGD). MB received financial support from Actelion to conduct her activities related to this study. MB, CEMH, INvS and AM have received consultancy fees from Actelion for participation in clinical trial programs and other projects, and CEMH, INvS and AM have received speaker fees for participation in scientific congresses and sponsored events. MB and CEMH donate all fees to the Gaucher Stichting, a national foundation that supports research in the field of lysosomal storage disorders. Consulting fees for INvS are donated to the Stichting Klinische Neurologie, a local foundation that supports research in the field of neurological disorders. DH has received consultancy fees from Actelion for participation in clinical trials, grants for local laboratory projects, and speaker fees for participation in scientific congresses and sponsored events. KEM, PG and LM have received speaker fees from Actelion for participation in sponsored events. PG received consultancy fees for participation in local clinical projects. LM received a travel grant from Actelion and was financially supported by TÁMOP 4.2.1./B-09/1/KONV-2010-0007 and TÁMOP 4.2.2-08/1-2008-0015. CN got speaker fees for participation in scientific meetings. KAW was sole shareholder of Cognitive Drug Research Ltd. Cognitive Drug Research Ltd supplied the CDR System for the study and received financial support from Actelion. KAW is currently an employee of United BioSource Corporation (UBC) that owns the CDR System since August 2009. CL is an employee of Actelion Pharmaceuticals Ltd. MP and MM report no conflicts of interest

The cognitive profile of type 1 Gaucher disease patients

BACKGROUND: The absence of neurological symptoms and signs is traditionally considered mandatory for a diagnosis of type 1 Gaucher disease (GD1), but in recent years many reports have emerged on neurological manifestations in GD1 patients. Nevertheless, it has been unclear whether cognitive deficits are part of the disease as well. METHODS: Cognitive function was assessed in a large cohort of GD1 patients with the use of the CDR system, a set of computerised cognitive tests. Testing was performed at baseline and every 6 months thereafter during a two-year study period. RESULTS: Our patient cohort (84 patients, median age 40 years, median time from diagnosis 15 years) showed mild deficits relative to healthy age-matched subjects on the composite scores: power of attention (Z-score (mean ± SD) -0.9 ± 1.37) and speed of memory (Z-score (mean ± SD) -1.39 ± 1.49). No decline in cognitive function was seen during the two-year period. Age correlated with the composite scores variability of attention and quality of working memory. Moreover, severely affected patients (Zimran severity score (SSI) ≥ 15) scored more poorly compared to mildly affected patients (SSI ≤ 5) on the composite measure power of attention, reflecting the ability to concentrate. CONCLUSIONS: GD1 patients exhibit mild deficits in power of attention and speed of memory, reflecting a decreased ability to focus attention and process information, together with a slowing in the speed of retrieval of items from memory. The clinical relevance of these findings is uncertain

Standardized and reproducible measurement of decision-making in mice

Progress in science requires standardized assays whose results can be readily shared, compared, and reproduced across laboratories. Reproducibility, however, has been a concern in neuroscience, particularly for measurements of mouse behavior. Here we show that a standardized task to probe decision-making in mice produces reproducible results across multiple laboratories. We designed a task for head-fixed mice that combines established assays of perceptual and value-based decision making, and we standardized training protocol and experimental hardware, software, and procedures. We trained 140 mice across seven laboratories in three countries, and we collected 5 million mouse choices into a publicly available database. Learning speed was variable across mice and laboratories, but once training was complete there were no significant differences in behavior across laboratories. Mice in different laboratories adopted similar reliance on visual stimuli, on past successes and failures, and on estimates of stimulus prior probability to guide their choices. These results reveal that a complex mouse behavior can be successfully reproduced across multiple laboratories. They establish a standard for reproducible rodent behavior, and provide an unprecedented dataset and open-access tools to study decision-making in mice. More generally, they indicate a path towards achieving reproducibility in neuroscience through collaborative open-science approaches

Denoising Two-Photon Calcium Imaging Data

Two-photon calcium imaging is now an important tool for in vivo imaging of biological systems. By enabling neuronal population imaging with subcellular resolution, this modality offers an approach for gaining a fundamental understanding of brain anatomy and physiology. Proper analysis of calcium imaging data requires denoising, that is separating the signal from complex physiological noise. To analyze two-photon brain imaging data, we present a signal plus colored noise model in which the signal is represented as harmonic regression and the correlated noise is represented as an order autoregressive process. We provide an efficient cyclic descent algorithm to compute approximate maximum likelihood parameter estimates by combing a weighted least-squares procedure with the Burg algorithm. We use Akaike information criterion to guide selection of the harmonic regression and the autoregressive model orders. Our flexible yet parsimonious modeling approach reliably separates stimulus-evoked fluorescence response from background activity and noise, assesses goodness of fit, and estimates confidence intervals and signal-to-noise ratio. This refined separation leads to appreciably enhanced image contrast for individual cells including clear delineation of subcellular details and network activity. The application of our approach to in vivo imaging data recorded in the ferret primary visual cortex demonstrates that our method yields substantially denoised signal estimates. We also provide a general Volterra series framework for deriving this and other signal plus correlated noise models for imaging. This approach to analyzing two-photon calcium imaging data may be readily adapted to other computational biology problems which apply correlated noise models.National Institutes of Health (U.S.) (DP1 OD003646-01)National Institutes of Health (U.S.) (R01EB006385-01)National Institutes of Health (U.S.) (EY07023)National Institutes of Health (U.S.) (EY017098

Cre-Dependent Expression of Multiple Transgenes in Isolated Neurons of the Adult Forebrain

Background: Transgenic mice with mosaic, Golgi-staining-like expression of enhanced green fluorescent protein (EGFP) have been very useful in studying the dynamics of neuronal structure and function. In order to further investigate the molecular events regulating structural plasticity, it would be useful to express multiple proteins in the same sparse neurons, allowing co-expression of functional proteins or co-labeling of subcellular compartments with other fluorescent proteins. However, it has been difficult to obtain reproducible expression in the same subset of neurons for direct comparison of neurons expressing different functional proteins. Principal Findings: Here we describe a Cre-transgenic line that allows reproducible expression of transgenic proteins of choice in a small number of neurons of the adult cortex, hippocampus, striatum, olfactory bulb, subiculum, hypothalamus, superior colliculus and amygdala. We show that using these Cre-transgenic mice, multiple Cre-dependent transgenes can be expressed together in the same isolated neurons. We also describe a Cre-dependent transgenic line expressing a membrane associated EGFP (EGFP-F). Crossed with the Cre-transgenic line, EGFP-F expression starts in the adolescent forebrain, is present in dendrites, dendritic protrusions, axons and boutons and is strong enough for acute or chronic in vivo imaging. Significance: This triple transgenic approach will aid the morphological and functional characterization of neurons in various Cre-dependent transgenic mice

Loss of Arc renders the visual cortex impervious to the effects of sensory experience or deprivation

A myriad of mechanisms have been suggested to account for the full richness of visual cortical plasticity. We found that visual cortex lacking Arc is impervious to the effects of deprivation or experience. Using intrinsic signal imaging and chronic visually evoked potential recordings, we found that Arc−/− mice did not exhibit depression of deprived-eye responses or a shift in ocular dominance after brief monocular deprivation. Extended deprivation also failed to elicit a shift in ocular dominance or open-eye potentiation. Moreover, Arc−/− mice lacked stimulus-selective response potentiation. Although Arc−/− mice exhibited normal visual acuity, baseline ocular dominance was abnormal and resembled that observed after dark-rearing. These data suggest that Arc is required for the experience-dependent processes that normally establish and modify synaptic connections in visual cortex.Howard Hughes Medical InstituteNational Science Foundation (U.S.

GABA Expression and Regulation by Sensory Experience in the Developing Visual System

The developing retinotectal system of the Xenopus laevis tadpole is a model of choice for studying visual experience-dependent circuit maturation in the intact animal. The neurotransmitter gamma-aminobutyric acid (GABA) has been shown to play a critical role in the formation of sensory circuits in this preparation, however a comprehensive neuroanatomical study of GABAergic cell distribution in the developing tadpole has not been conducted. We report a detailed description of the spatial expression of GABA immunoreactivity in the Xenopus laevis tadpole brain at two key developmental stages: stage 40/42 around the onset of retinotectal innervation and stage 47 when the retinotectal circuit supports visually-guided behavior. During this period, GABAergic neurons within specific brain structures appeared to redistribute from clusters of neuronal somata to a sparser, more uniform distribution. Furthermore, we found that GABA levels were regulated by recent sensory experience. Both ELISA measurements of GABA concentration and quantitative analysis of GABA immunoreactivity in tissue sections from the optic tectum show that GABA increased in response to a 4 hr period of enhanced visual stimulation in stage 47 tadpoles. These observations reveal a remarkable degree of adaptability of GABAergic neurons in the developing brain, consistent with their key contributions to circuit development and function

Microglial Interactions with Synapses Are Modulated by Visual Experience

Microglia, the brain's immune cells, show unique interactions with nearby synaptic elements under non-pathological conditions that are sensitive to changes in sensory experience