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Reimer, J.

Publications and source records attributed to Reimer, J..

5 recordsLinked to original sources

Stimulus domain transfer in recurrent models for large scale cortical population prediction on video

To better understand the representations in visual cortex, we need to generate better predictions of neural activity in awake animals presented with their ecological input: natural video. Despite recent advances in models for static images, models for predicting responses to natural video are scarce and standard linear-nonlinear models perform poorly. We developed a new deep recurrent network architecture that predicts inferred spiking activity of thousands of mouse V1 neurons simulta-neously recorded with two-photon microscopy, while accounting for confounding factors such as the animals gaze position and brain state changes related to running state and pupil dilation. Powerful system identification models provide an opportunity to gain insight into cortical functions through in silico experiments that can subsequently be tested in the brain. However, in many cases this approach requires that the model is able to generalize to stimulus statistics that it was not trained on, such as band-limited noise and other parameterized stimuli. We investigated these domain transfer properties in our model and find that our model trained on natural images is able to correctly predict the orientation tuning of neurons in responses to artificial noise stimuli. Finally, we show that we can fully generalize from movies to noise and maintain high predictive performance on both stimulus domains by fine-tuning only the final layers weights on a network otherwise trained on natural movies. The converse, however, is not true.

neuroscience

Optogenetic manipulation of medullary neurons in the locust optic lobe

Locust is a widely used animal model for studying sensory processing and its relation to behavior. Due to the lack of genomic information, genetic tools to manipulate neural circuits in locusts are not yet available. We examined whether Semliki Forest virus is suitable to mediate exogenous gene expression in neurons of the locust optic lobe. We subcloned a channelrhodopsin variant and the yellow fluorescent protein Venus into a Semliki Forest virus vector and injected the virus into the optic lobe of locusts (Schistocerca americana). Fluorescence was observed in all injected optic lobes. Most neurons that expressed the recombinant proteins were located in the first two neuropils of the optic lobe, the lamina and medulla. Extracellular recordings demonstrated that laser illumination increased the firing rate of medullary neurons expressing channelrhodopsin. The optogenetic activation of the medullary neurons also triggered firing of a postsynaptic, looming-sensitive neuron, the Lobula Giant Movement Detector (LGMD). These results indicate that Semliki Forest virus is efficient at mediating transient exogenous gene expression and provides a tool to manipulate neural circuits in the locust nervous system and likely other insects.\n\nNew and NoteworthyUsing Semliki Forest virus, we efficiently delivered channelrhodopsin into neurons of the locust optic lobe. We demonstrate that laser illumination increases the firing of the medullary neurons expressing channelrhodopsin and of an identified postsynaptic target neuron, the LGMD neuron. This technique allows to manipulate the neuronal activity in locust neural circuits using optogenetics.

neuroscience

Penalized matrix decomposition for denoising, compression, and improved demixing of functional imaging data

Calcium imaging has revolutionized systems neuroscience, providing the ability to image large neural populations with single-cell resolution. The resulting datasets are quite large (with scales of TB/hour in some cases), which has presented a barrier to routine open sharing of this data, slowing progress in reproducible research. State of the art methods for analyzing this data are based on non-negative matrix factorization (NMF); these approaches solve a non-convex optimization problem, and are highly effective when good initializations are available, but can break down e.g. in low-SNR settings where common initialization approaches fail.\n\nHere we introduce an improved approach to compressing and denoising functional imaging data. The method is based on a spatially-localized penalized matrix decomposition (PMD) of the data to separate (low-dimensional) signal from (temporally-uncorrelated) noise. This approach can be applied in parallel on local spatial patches and is therefore highly scalable, does not impose non-negativity constraints or require stringent identifiability assumptions (leading to significantly more robust results compared to NMF), and estimates all parameters directly from the data, so no hand-tuning is required. We have applied the method to a wide range of functional imaging data (including one-photon, two-photon, three-photon, widefield, somatic, axonal, dendritic, calcium, and voltage imaging datasets): in all cases, we observe ~2-4x increases in SNR and compression rates of 20-300x with minimal visible loss of signal, with no adjustment of hyperparameters; this in turn facilitates the process of demixing the observed activity into contributions from individual neurons. We focus on two challenging applications: dendritic calcium imaging data and voltage imaging data in the context of optogenetic stimulation. In both cases, we show that our new approach leads to faster and much more robust extraction of activity from the video data.

neuroscience

Community-based benchmarking improves spike inference from two-photon calcium imaging data

In recent years, two-photon calcium imaging has become a standard tool to probe the function of neural circuits and to study computations in neuronal populations1, 2. However, the acquired signal is only an indirect measurement of neural activity due to the comparatively slow dynamics of fluorescent calcium indicators3. Different algorithms for estimating spike trains from noisy calcium measurements have been proposed in the past4-8, but it is an open question how far performance can be improved. Here, we report the results of the spikefinder challenge, launched to catalyze the development of new spike inference algorithms through crowd-sourcing. We present ten of the submitted algorithms which show improved performance compared to previously evaluated methods. Interestingly, the top-performing algorithms are based on a wide range of principles from deep neural networks to generative models, yet provide highly correlated estimates of the neural activity. The competition shows that benchmark challenges can drive algorithmic developments in neuroscience.

neuroscience

Refinement of intraperitoneal injection of sodium pentobarbital for euthanasia inlaboratory rats (Rattus norvegicus)

BackgroundThe Canadian Council on Animal Care and American Veterinary Medical Association classify intraperitoneal (IP) pentobarbital as an acceptable euthanasia method in rats. However, federal guidelines do not exist for a recommended dose or volume and IP euthanasia has been described as unreliable, with misinjections leading to variable success in ensuring a timely death. The aims of this study were to assess and improve efficacy and consistency of IP euthanasia.\n\nMethodsIn a randomized, blinded study, 51 adult female Sprague-Dawley rats (170-495 g) received one of four treatments: low-dose low-volume (LL) IP pentobarbital (n = 13, 200 mg/kg pentobarbital), low-dose high-volume (LH) IP pentobarbital (n = 14, 200 mg/kg diluted 1:3 with phosphate buffered saline), high-dose high-volume (HH, n = 14, 800 mg/kg pentobarbital), or saline. Times to loss of righting reflex (LORR) and cessation of heartbeat (CHB) were recorded. To identify misinjections, necropsy examinations were performed on all rats. Video recordings of LL and HH groups were analyzed for pain-associated behaviors. Between-group comparisons were performed with 1-way ANOVA and Games-Howell post hoc tests. Variability for CHB was assessed by coefficient of variation (CV) calculation.\n\nResultsThe fastest euthanasia method (CHB) was HH (283.7 {+/-} 38 s), compared with LL (485.8 {+/-} 140.7 s, p = 0.002) and LH (347.7 {+/-} 72.0 s, p = 0.039). Values for CV were: HH, 13.4%; LH, 20.7%; LL, 29.0%. LORR time was longest in LL (139.5 {+/-} 29.6 s), compared with HH (111.6 {+/-} 19.7 s, p = 0.046) and LH (104.2 {+/-} 19.3 s, p = 0.01). Misinjections occurred in 15.7% (8/51) of euthanasia attempts. Pain-associated behavior incidence ranged from 36% (LL) to 46% (HH).\n\nConclusionThese data illustrate refinement of this euthanasia technique. Both dose and volume contribute to speed of death with IP pentobarbital and an increase in volume alone does not significantly reduce variability. The proportion of misinjections was similar to that of previous studies.\n\nAbbreviations

physiology