Dimensionality reduction of calcium-imaged neuronal population activity.

Calcium imaging has been widely adopted for its ability to record from large neuronal populations. To summarize the time course of neural activity, dimensionality reduction methods, which have been applied extensively to population spiking activity, may be particularly useful. However, it is unclear if the dimensionality reduction methods applied to spiking activity are appropriate for calcium imaging. We thus carried out a systematic study of design choices based on standard dimensionality reduction methods. We also developed a method to perform deconvolution and dimensionality reduction simultaneously (Calcium Imaging Linear Dynamical System, CILDS). CILDS most accurately recovered the single-trial, low-dimensional time courses from simulated calcium imaging data. CILDS also outperformed the other methods on calcium imaging recordings from larval zebrafish and mice. More broadly, this study represents a foundation for summarizing calcium imaging recordings of large neuronal populations using dimensionality reduction in diverse experimental settings.

Visual experience has opposing influences on the quality of stimulus representation in adult primary visual cortex.

Transient dark exposure, typically 7-10 days in duration, followed by light reintroduction is an emerging treatment for improving the restoration of vision in amblyopic subjects whose occlusion is removed in adulthood. Dark exposure initiates homeostatic mechanisms that together with light-induced changes in cellular signaling pathways result in the re-engagement of juvenile-like plasticity in the adult such that previously deprived inputs can gain cortical territory. It is possible that dark exposure itself degrades visual responses, and this could place constraints on the optimal duration of dark exposure treatment. To determine whether eight days of dark exposure has a lasting negative impact on responses to classic grating stimuli, neural activity was recorded before and after dark exposure in awake head-fixed mice using two-photon calcium imaging. Neural discriminability, assessed using classifiers, was transiently reduced following dark exposure; a decrease in response reliability across a broad range of spatial frequencies likely contributed to the disruption. Both discriminability and reliability recovered. Fixed classifiers were used to demonstrate that stimulus representation rebounded to the original, pre-deprivation state, thus dark exposure did not appear to have a lasting negative impact on visual processing. Unexpectedly, we found that dark exposure significantly stabilized orientation preference and signal correlation. Our results reveal that natural vision exerts a disrupting influence on the stability of stimulus preference for classic grating stimuli and, at the same time, improves neural discriminability for both low and high-spatial frequency stimuli.

Existing function in primary visual cortex is not perturbed by new skill acquisition of a non-matched sensory task.

Acquisition of new skills has the potential to disturb existing network function. To directly assess whether previously acquired cortical function is altered during learning, mice were trained in an abstract task in which selected activity patterns were rewarded using an optical brain-computer interface device coupled to primary visual cortex (V1) neurons. Excitatory neurons were longitudinally recorded using 2-photon calcium imaging. Despite significant changes in local neural activity during task performance, tuning properties and stimulus encoding assessed outside of the trained context were not perturbed. Similarly, stimulus tuning was stable in neurons that remained responsive following a different, visual discrimination training task. However, visual discrimination training increased the rate of representational drift. Our results indicate that while some forms of perceptual learning may modify the contribution of individual neurons to stimulus encoding, new skill learning is not inherently disruptive to the quality of stimulus representation in adult V1.

Development of Natural Scene Representation in Primary Visual Cortex Requires Early Postnatal Experience.

The development of the visual system is known to be shaped by early-life experience. To identify response properties that contribute to enhanced natural scene representation, we performed calcium imaging of excitatory neurons in the primary visual cortex (V1) of awake mice raised in three different conditions (standard-reared, dark-reared, and delayed-visual experience) and compared neuronal responses to natural scene features in relation to simpler grating stimuli that varied in orientation and spatial frequency. We assessed population selectivity in the V1 by using decoding methods and found that natural scene discriminability increased by 75% between the ages of 4 and 6 weeks. Both natural scene and grating discriminability were higher in standard-reared animals than in those raised in the dark. This increase in discriminability was accompanied by a reduction in the number of neurons that responded to low-spatial-frequency gratings. At the same time, there was an increase in neuronal preference for natural scenes. Light exposure restricted to a 2- to 4-week window during adulthood did not induce improvements in natural scene or in grating stimulus discriminability. Our results demonstrate that experience reduces the number of neurons needed to effectively encode grating stimuli and that early visual experience enhances natural scene discriminability by directly increasing responsiveness to natural scene features.

Feature selectivity is stable in primary visual cortex across a range of spatial frequencies.

Reliable perception of environmental signals is a critical first step to generating appropriate responses and actions in awake behaving animals. The extent to which stimulus features are stably represented at the level of individual neurons is not well understood. To address this issue, we investigated the persistence of stimulus response tuning over the course of 1-2 weeks in the primary visual cortex of awake, adult mice. Using 2-photon calcium imaging, we directly compared tuning stability to two stimulus features (orientation and spatial frequency) within the same neurons, specifically in layer 2/3 excitatory neurons. The majority of neurons that were tracked and tuned on consecutive imaging sessions maintained stable orientation and spatial frequency preferences (83% and 76% of the population, respectively) over a 2-week period. Selectivity, measured as orientation and spatial frequency bandwidth, was also stable. Taking into account all 4 parameters, we found that the proportion of stable neurons was less than two thirds (57%). Thus, a substantial fraction of neurons (43%) were unstable in at least one parameter. Furthermore, we found that instability of orientation preference was not predictive of instability of spatial frequency preference within the same neurons. Population analysis revealed that noise correlation values were stable well beyond the estimated decline in monosynaptic connectivity (~250-300 microns). Our results demonstrate that orientation preference is stable across a range of spatial frequencies and that the tuning of distinct stimulus features can be independently maintained within a single neuron.