Biology subjects

Lawlor, J.

Publications and source records attributed to Lawlor, J..

5 recordsLinked to original sources

bioRxiv2025

Fast and accessible morphology-free functional fluorescence imaging analysis

Optical calcium imaging is a powerful tool for recording neural activity across a wide range of spatial scales, from dendrites and spines to whole-brain imaging through two-photon and widefield microscopy. Traditional methods for analyzing functional calcium imaging data rely heavily on spatial features, such as the compact shapes of somas, to extract regions of interest and their associated temporal traces. This spatial dependency can introduce biases in time trace estimation and limit the applicability of these methods across different neuronal morphologies and imaging scales. To address these limitations, the Graph Filtered Temporal Dictionary Learning (GraFT) uses a graph-based approach to identify neural components based on shared temporal activity rather than spatial proximity, enhancing generalizability across diverse datasets. Here we present significant advancements to the GraFT algorithm, including the integration of a more efficient solver for the L1 least absolute shrinkage and selection operator (LASSO) problem and the application of compressive sensing techniques to reduce computational complexity. By employing random projections to reduce data dimensionality, we achieve substantial speedups while maintaining analytical accuracy. These advancements significantly accelerate the GraFT algorithm, making it more scalable for larger and more complex datasets. Moreover, to increase accessibility, we developed a graphical user interface to facilitate running and analyzing the outputs of GraFT. Finally, we demonstrate the utility of GraFT to imaging data beyond meso-scale imaging, including vascular and axonal imaging.

bioinformatics↗

bioRxiv2025

Revealing hidden knowledge in amnestic mice

Alzheimers disease (AD) is a form of dementia in which memory and cognitive decline is thought to arise from underlying neurodegeneration. These cognitive impairments, however, are transient when they first appear and can fluctuate across disease progression. Here, we investigate the neural mechanisms underlying fluctuations of performance in amnestic mice. We trained APP/PS1+ mice on an auditory go/no-go task that dissociated learning of task contingencies (knowledge) from its more variable expression under reinforcement (performance). APP/PS1+ exhibited significant performance deficits compared to control mice. Using large-scale two-photon imaging of 6,216 excitatory neurons in 8 mice, we found that auditory cortical networks were more suppressed, less selective to the sensory cues, and exhibited aberrant higher-order encoding of reward prediction compared to control mice. A small sub-population of neurons, however, displayed the opposite phenotype, reflecting a potential compensatory mechanism. Volumetric analysis demonstrated that deficits were concentrated near A{beta} plaques. Strikingly, we found that these cortical deficits were reversed almost instantaneously on probe (non-reinforced) trials when APP/PS1+ performed as well as control mice, providing neural evidence for intact stimulus-action knowledge despite variable ongoing performance. A biologically-plausible reinforcement learning model recapitulated these results and showed that synaptic weights from sensory-to-decision neurons were preserved (i.e. intact stimulus-action knowledge) despite poor performance that was due to inadequate contextual scaling (i.e. impaired performance). Our results suggest that the amnestic phenotype is transient, contextual, and endogenously reversible, with the underlying neural circuits retaining the underlying stimulus-action associations. Thus, memory deficits commonly observed in amnestic mouse models, and potentially at early stages of dementia in humans, relate more to contextual drivers of performance rather than degeneration of the underlying memory traces.

neuroscience↗

bioRxiv2023

Spatially clustered neurons encode vocalization categories in the bat midbrain

Rapid categorization of vocalizations enables adaptive behavior across species. While categorical perception is thought to arise in the neocortex, humans and other animals could benefit from functional organization of ethologically-relevant sounds at earlier stages in the auditory hierarchy. Here, we developed two-photon calcium imaging in the awake echolocating bat (Eptesicus fuscus) to study encoding of sound meaning in the Inferior Colliculus, which is as few as two synapses from the inner ear. Echolocating bats produce and interpret frequency sweep-based vocalizations for social communication and navigation. Auditory playback experiments demonstrated that individual neurons responded selectively to social or navigation calls, enabling robust population-level decoding across categories. Strikingly, category-selective neurons formed spatial clusters, independent of tonotopy within the IC. These findings support a revised view of categorical processing in which specified channels for ethologically-relevant sounds are spatially segregated early in the auditory hierarchy, enabling rapid subcortical organization of call meaning.

neuroscience↗

bioRxiv2022

A parallel channel of state-dependent sensory signaling from the cholinergic basal forebrain to the auditory cortex

Cholinergic basal forebrain (CBF) signaling exhibits multiple timescales of activity with classic, slow signals related to brain and behavioral states and faster, phasic signals reflecting behavioral events, including movement and reinforcement. Recent evidence suggests that the CBF may also exhibit fast, sensory-evoked responses. It remains unknown, however, whether such sensory signals target the sensory cortex and how they relate to local functional topography. Moreover, the extent to which fast and slow CBF activity interact has been largely unexplored. Here, we used simultaneous two-channel, two-photon imaging of CBF axons and auditory cortical (AC) neurons to reveal that CBF axons project a robust, non-habituating, and stimulus-specific sensory signal to the AC. Individual axon segments exhibited heterogeneous but stable tuning to auditory stimuli allowing stimulus identity to be decoded from the population. However, CBF axons displayed no tonotopy and their frequency tuning was uncoupled from that of nearby cortical neurons. Chemogenetic suppression revealed the auditory thalamus as a principal source of auditory information to the CBF. Finally, slow fluctuations in cholinergic activity modulated the fast, sensory-evoked signals in the same axons, suggesting that a multiplexed combination of fast and slow signals is projected from the CBF to the AC. Taken together, our work demonstrates a novel, non-canonical function of the CBF as a parallel channel of state-dependent sensory signaling to the sensory cortex that provides repeated representations of a broad range of sound stimuli at all points on the tonotopic map.

neuroscience↗

bioRxiv2021

Hidden temporal structure of the ongoing task impacts detection strategy and is reflected in pupillary dynamics

Estimating temporal regularities in incoming sensory inputs supports optimal decisions in noisy environments. In particular, inferred temporal structure can ease the detection of likely target events. Here we postulated that timely urgency signals can adapt subjects decision-making to the ongoing task temporal structure, possibly through neuromodulatory tone. To test this hypothesis, we used an auditory change detection task in which targets followed a block-based temporal contingency, unbeknownst to participants. False alarm occurrences were driven by the distribution of target timings, indicating that participants adapted their behavior to the ongoing temporal structure. Task-evoked pupillary responses were larger for blocks with earliest target timings, and correlated with individual subjects behavioral adaptation. Individual pupil responses matched an urgency signal extracted from a decision model fitted to behavior. This work demonstrates that internal temporal expectation can be tracked through pupillary dynamics, suggesting a role of neuromodulatory systems in context-dependent modulation of decision variable dynamics.

neuroscience↗