Biology subjects

Wahl, A.-S.

Publications and source records attributed to Wahl, A.-S..

5 recordsLinked to original sources

bioRxiv2026

Layer-specific wide-field calcium imaging of neocortical activity

The mammalian neocortex is highly organized in local microcircuits and through long-range projection patterns between different regions. Since various features of local and long-range connectivity are determined by the cortical layer in which the respective neurons reside, understanding the flow of cortical information within and across layers is essential. Wide-field calcium imaging enables mesoscale functional mapping of genetically identified neurons across cortical areas. However, it has been applied primarily to superficial cortical layers, and systematic comparisons of wide-field signals across cortical layers are scarce. Here, we apply wide-field calcium imaging to different cortical layers using transgenic mouse lines with selective expression of GCaMP6f in layers 2/3, 5, and 6. We address several challenges of layer-specific wide-field imaging and provide possible solutions. First, to improve the registration of functional data to standard atlases, we demonstrate the benefit of layer-specific registration maps that are warped on the basis of the depth-dependent surface projections of the labeled cell populations. These maps help to assign the imaged calcium signals to the specific regions from which they originate. Second, we measure the depth-dependent blurring of wide-field fluorescence signals induced by light scattering and reveal stronger blurring in deep vs. superficial layers, in line with previous theoretical predictions from simulations. We used measured point spread functions to deconvolve single-whisker-evoked calcium signals in the barrel cortex and demonstrate improved signal confinement to individual barrel columns across layers. Finally, we investigate cross-regional functional connectivity during awake resting state periods for distinct layers. We find that mesoscopic functional connectivity is largely conserved between the cortical layers, with subtle differences for key regions of the default mode network (retrosplenial cortex and medial prefrontal cortex). Our approaches facilitate the comprehensive characterization of layer-specific cortico-cortical interactions, expanding wide-field calcium imaging as a powerful tool to investigate the layered organization of distributed brain dynamics.

neuroscience↗

bioRxiv2025

Contralesional activity reflects compensation, while brainstem detour pathways support skilled motor recovery after stroke

Large strokes frequently result in lasting motor deficits and trigger extensive reorganization within the brain and spinal cord. Altered neuronal activity in the contralesional hemisphere has been documented in both humans and rodent models, yet its role in functional recovery versus maladaptation remains unresolved. Here, we used chronic wide-field calcium imaging to monitor bilateral cortical activity in mice performing a skilled reach-to-grasp task before and days to weeks after stroke. Strokes produced persistent fine motor impairments, which were only partly alleviated by intensive rehabilitative training. While cortical activity was in particular suppressed in the ipsilesional cortex after stroke, training promoted sustained increases in contralesional sensorimotor activity. However, ridge regression analysis of neural and behavioral data indicated that this activity largely reflected compensatory use of the intact paw rather than recovery of the impaired forelimb. Axonal tracing nevertheless revealed enhanced projections from contralesional motor cortex to ipsilesional brainstem nuclei - including the midbrain and pontine reticular nucleus - specifically in trained animals. These findings identify a rehabilitation-induced corticofugal pathway supporting motor recovery, highlighting a target for neuromodulation strategies in chronic post-stroke impairment.

neuroscience↗

bioRxiv2024

Brain-wide microstrokes affect the stability of memory circuits in the hippocampus

Cognitive deficits affect over 70% of stroke survivors, yet the mechanisms by which multiple small ischemic events contribute to cognitive decline remain poorly understood. In this study, we employed chronic two-photon calcium imaging to longitudinally track the fate of individual neurons in the hippocampus of mice navigating a virtual reality environment, both before and after inducing brain-wide microstrokes. Our findings reveal that, under normal conditions, hippocampal neurons exhibit varying degrees of stability in their spatial memory coding. However, microstrokes disrupted this functional network architecture, leading to cognitive impairments. Notably, the preservation of stable coding place cells, along with the stability, precision, and persistence of the hippocampal network, was strongly predictive of cognitive outcomes. Mice with more synchronously active place cells near important locations demonstrated recovery from cognitive impairment. This study uncovers critical cellular responses and network alterations following brain injury, providing a foundation for novel therapeutic strategies preventing cognitive decline.

neuroscience↗

bioRxiv2022

EXPLORE: A novel deep learning-based analysis method for exploration behaviour in object recognition tests

Object recognition tests are widely used in neuroscience to assess memory function in rodents. Despite the experimental simplicity of the task, the interpretation of behavioural features that are counted as object exploration can be complicated. Thus, object exploration is often analysed by manual scoring, which is time-consuming and variable across researchers. Current software using tracking points often lacks precision in capturing complex ethological behaviour. Switching or losing tracking points can bias outcome measures. To overcome these limitations we developed "EXPLORE", a simple, ready-to use and open source pipeline. EXPLORE consists of a convolutional neural network trained in a supervised manner, that extracts features from images and classifies behaviour of rodents near a presented object. EXPLORE achieves human-level accuracy in identifying and scoring exploration behaviour and outperforms commercial software with higher precision, higher versatility and lower time investment, in particular in complex situations. By labeling the respective training data set, users decide by themselves, which types of animal interactions on objects are in- or excluded, ensuring a precise analysis of exploration behaviour. A set of graphical user interfaces (GUIs) provides a beginning-to-end analysis of object recognition tests, accelerating a fast and reproducible data analysis without the need of expertise in programming or deep learning.

animal behavior and cognition↗

bioRxiv2019

Context-dependent limb movement encoding in neuronal populations of motor cortex

Neuronal networks of the mammalian motor cortex (M1) are important for dexterous control of limb joints. Yet it remains unclear how encoding of joint movement in M1 networks depends on varying environmental contexts. Using calcium imaging we measured neuronal activity in layer 2/3 of the mouse M1 forelimb region while mice grasped either regularly or irregularly spaced ladder rungs during locomotion. We found that population coding of forelimb joint movements is sparse and varies according to the flexibility demanded from them in the regular and irregular context, even for equivalent grasping actions across conditions. This context-dependence of M1 network encoding emerged during learning of the locomotion task, fostered more precise grasping actions, but broke apart upon silencing of projections from secondary motor cortex (M2). These findings suggest that M2 reconfigures M1 neuronal circuits to adapt joint processing to the flexibility demands in specific familiar contexts, thereby increasing the accuracy of motor output.

neuroscience↗