Biology subjects

Ollerenshaw, D. R.

Publications and source records attributed to Ollerenshaw, D. R..

10 recordsLinked to original sources

bioRxiv2026

Topographic structure and function of locus coeruleus norepinephrine neurons

Norepinephrine (NE) is released throughout most of the central nervous system by neurons in the locus coeruleus (LC). We found a relationship between the morphologies, gene expression, and activity of LC-NE neurons in mice. Axonal projections of individual neurons were extensive but largely confined to subsets of brain regions. Axonal projections and graded gene expression correlated with locations of cell bodies in LC. In a behavioral task requiring ongoing learning from actions, neurons in dorsal LC projecting to the cerebral cortex were excited when mice made a different choice from the previous one and by reward prediction errors, a signal driving learning. Background activity of neurons in ventral LC was higher when mice ignored stimuli indicating potential reward availability. These observations reveal a topographically organized structure and function of a neurotransmitter system and show that it contains learning signals for flexible behavior.

neuroscience↗

bioRxiv2022

Influence of claustrum on cortex varies by area, layer, and cell type

The claustrum is a small subcortical structure with widespread connections with disparate regions of the cortex. These far-reaching projections have led to many hypotheses concerning its function. However, we know little about how claustrum input affects neural activity in cortex, particularly beyond frontal areas. Here, using optogenetics and multi-regional Neuropixels recordings from over 15,000 neurons in awake mice, we demonstrate that the effect of claustrum input differs depending on brain area, layer, and cell type. Brief claustrum stimulation produces approximately 1 spike per claustrum neuron, which affects many fast-spiking (FS; putative inhibitory) but very few regular-spiking (RS; putative excitatory) cortical neurons. Prolonged claustrum stimulation affects many more cortical FS and RS neurons. More inhibition occurs in frontal regions and deeper layers, while more excitation occurs in posterior regions and superficial layers. These differences imply that the function of claustrum input to cortex depends on the area, supporting the idea that claustro-cortical circuits are organized into functional modules.

neuroscience↗

bioRxiv2021

Anterior claustrum cells are responsive during behavior but not passive sensory stimulation

The claustrum is uniquely positioned to communicate with almost all higher-order cortical areas through widespread and reciprocal anatomical projections, yet the in vivo functional properties of claustrum neurons are not well understood. Here we use microendoscope imaging in mice to measure activity in populations of genetically-labelled Gnb4+ claustrum neurons. We find that only a small fraction of cells in the anterior claustrum are responsive to visual or auditory stimuli when delivered under passive yet wakeful conditions. In contrast, during a visual behavioral task, the majority of cells in the anterior claustrum are strongly modulated, with separate and spatially intermingled cell populations showing either increases or decreases in activity relative to spontaneous levels. Our results suggest that the Gnb4+ cells in the anterior claustrum do not represent passively presented sensory stimuli; rather, these cells are strongly engaged during behavior associated with sensory-motor transformations.

neuroscience↗

bioRxiv2020

Adaptation supports short-term memory in a visual change detection task

The maintenance of short-term memories is critical for survival in a dynamically changing world. Previous studies suggest that this memory can be stored in the form of persistent neural activity or using a synaptic mechanism, such as with short-term plasticity. Here, we compare the predictions of these two mechanisms to neural and behavioral measurements in a visual change detection task. Mice were trained to respond to changes in a repeated sequence of natural images while neural activity was recorded using two-photon calcium imaging. We also trained two types of artificial neural networks on the same change detection task as the mice. Following fixed pre-processing using a pretrained convolutional neural network, either a recurrent neural network (RNN) or a feedforward neural network with short-term synaptic depression (STPNet) was trained to the same level of performance as the mice. While both networks are able to learn the task, the STPNet model contains units whose activity are more similar to the in vivo data and produces errors which are more similar to the mice. When images are omitted, an unexpected perturbation which was absent during training, mice often do not respond to the omission but are more likely to respond to the subsequent image. Unlike the RNN model, STPNet also produces a similar pattern of behavior. These results suggest that simple neural adaptation mechanisms may serve as an important bottom-up memory signal in this task, which can be used by downstream areas in the decision-making process. Author SummaryAnimals have to adapt to environments with rich dynamics and maintain multiple types of memories. In this study, we focus on a visual change detection task in mice which requires short-term memory. Learning which features need to be maintained in short-term memory can be realized in a recurrent neural network by changing connections in the network, resulting in memory maintenance through persistent activity. However, in biological networks, a large diversity of time-dependent intrinsic mechanisms are also available. As an alternative to persistent neural activity, we find that learning to make use of internal adapting dynamics better matches both the observed neural activity and behavior of animals in this simple task. The presence of a large diversity of temporal traces could be one of the reasons for the diversity of cells observed. We believe that both learning to keep representations of relevant stimuli in persistent activity and learning to make use of intrinsic time-dependent mechanisms exist, and their relative use will be dependent on the exact task.

neuroscience↗

bioRxiv2020

Similar visual perception in GCaMP6 transgenic mice despite differences in learning and motivation

To study mechanisms of perception and cognition, neural measurements must be made during behavior. A goal of the Allen Brain Observatory is to map activity in distinct cortical cell classes during visual processing and behavior. Here we characterize learning and performance of five GCaMP6-expressing transgenic lines trained on a visual change detection task. We used automated training procedures to facilitate comparisons across mice. Training times varied, but most transgenic mice learned the task. Motivation levels also varied across mice. To compare mice in similar motivational states we subdivided sessions into over-, under-, and optimally motivated periods. When motivated, the pattern of perceptual decisions were highly correlated across transgenic lines, although overall d-prime was lower in one line labeling somatostatin inhibitory cells. These results provide important context for using these mice to map neural activity underlying perception and behavior.

neuroscience↗

bioRxiv2019

Quantifying and Modelling Transfer Learning in Mice Between Consecutive Training Stages of a Change Detection Task

Animals are known to be able to rapidly transfer knowledge between tasks with similar structure. We trained a set of mice on a visual change detection task with multiple stages, starting with direct transitions between gratings, adding an intervening gray screen, and subsequently moving to multiple sets of natural images. We observe that, when progressing to new stages, the performance increases very fast. However, when transitioning to a task of higher complexity, the peak performance decreases. This setup facilitates for the first time an experimental platform to study the transfer learning phenomena in mice using visual stimuli. Based on these results and additional neuroscience insight, we propose a cognitive model to explain the quick adaptation observed in mice. It extends a deep Q learning agent with a multi-tiered architecture and the possibility of performing a representation remapping at every level of the hierarchy to prevent the downstream propagation of representation anomalies. This architecture provides the substrate of an adaptation algorithm based on ideas of optimal transport of probability distributions. It matches well key behavioral aspects observed in mice and the experimental constraint that the mice are initially trained using a single task variant before it transitions to the new training phase. The modelling process helped us to gain biological insights: first, the optimal transport mechanism of the representation remapping indicated that a possible reason for the reduced performance when mice move to a new more complex task could be due to limited representation resources which were optimized for the previous task. Second, the multi-tiered architecture was first an engineering constraint and later a biologic insight confirmed by the literature. A final insight came from the computations required to perform the representation remapping. These computations are interesting because they could help to confirm this transfer learning theory by looking for similar neural correlates during the adaptation process.

animal behavior and cognition↗

bioRxiv2019

Experience shapes activity dynamics and stimulus coding of VIP inhibitory and excitatory cells

Cortical circuits are flexible and can change with experience and learning. However, the effects of experience on specific cell types, including distinct inhibitory types, are not well understood. Here we investigated how excitatory and VIP inhibitory cells in layer 2/3 of mouse visual cortex were impacted by visual experience in the context of a behavioral task. Mice learned to perform an image change detection task with a set of eight natural scene images, viewing these images thousands of times. Subsequently, during 2-photon imaging experiments, mice performed the task with these familiar images and three additional sets of novel images. Novel images evoked stronger overall activity in both excitatory and VIP populations, and familiar images were more sparsely coded by excitatory cells. The temporal dynamics of VIP activity differed markedly between novel and familiar images: VIP cells were stimulus-driven by novel images but displayed ramping activity during the inter-stimulus interval for familiar images. Moreover, when a familiar stimulus was omitted from an expected sequence, VIP cells showed extended ramping activity until the subsequent image presentation. This prominent shift in response dynamics suggests that VIP cells may adopt different modes of processing during familiar versus novel conditions.\n\nHIGHLIGHTSO_LIExperience with natural images in a change detection task reduces overall activity of cortical excitatory and VIP inhibitory cells\nC_LIO_LIEncoding of natural images is sharpened with experience in excitatory neurons\nC_LIO_LIVIP cells are stimulus-driven by novel images but show pre-stimulus ramping for familiar images\nC_LIO_LIVIP cells show strong ramping activity during the omission of an expected stimulus\nC_LI

neuroscience↗

bioRxiv2017

A suite of transgenic driver and reporter mouse lines with enhanced brain cell type targeting and functionality

Modern genetic approaches are powerful in providing access to diverse types of neurons within the mammalian brain and greatly facilitating the study of their function. We here report a large set of driver and reporter transgenic mouse lines, including 23 new driver lines targeting a variety of cortical and subcortical cell populations and 26 new reporter lines expressing an array of molecular tools. In particular, we describe the TIGRE2.0 transgenic platform and introduce Cre-dependent reporter lines that enable optical physiology, optogenetics, and sparse labeling of genetically-defined cell populations. TIGRE2.0 reporters broke the barrier in transgene expression level of single-copy targeted-insertion transgenesis in a wide range of neuronal types, along with additional advantage of a simplified breeding strategy compared to our first-generation TIGRE lines. These novel transgenic lines greatly expand the repertoire of high-precision genetic tools available to effectively identify, monitor, and manipulate distinct cell types in the mouse brain.

neuroscience↗

bioRxiv2017

Mouse hue and wavelength-specific luminance contrast sensitivity are non-uniform across visual space

Mammalian visual behaviors, as well as responses in the neural systems thought to underlie these behaviors, are driven by luminance and hue contrast. With tools for measuring activity in cell-type specific populations in the mouse during visual behavior gaining traction, it is important to define the extent of luminance and hue information that is behaviorally-accessible to the mouse. A non-uniform distribution of cone opsins in the mouse potentially complicates both luminance and hue sensitivity: opposing gradients of short (UV-shifted) and middle (blue/green) cone opsins suggest that hue discrimination and wavelength-specific luminance contrast sensitivity may differ depending on retinotopic location. Here we ask if, and how well, mice can discriminate color and wavelength-specific luminance across visuotopic space. We found that mice were able to discriminate hue, and were able to do so more broadly across visuotopic space than expected from the cone-opsin distribution. We also found wavelength-band specific differences in luminance sensitivity.

neuroscience↗

bioRxiv2017

Aberrant Cortical Activity In Multiple GCaMP6-Expressing Transgenic Mouse Lines

Transgenic mouse lines are invaluable tools for neuroscience but as with any technique, care must be taken to ensure that the tool itself does not unduly affect the system under study. Here we report aberrant electrical activity, similar to interictal spikes, and accompanying fluorescence events in some genotypes of transgenic mice expressing GCaMP6 genetically-encoded calcium sensors. These epileptiform events have been observed particularly, but not exclusively, in mice with Emx1-Cre and Ai93 transgenes, across multiple laboratories. The events occur at >0.1 Hz, are very large in amplitude (>1.0 mV local field potentials, >10% df/f widefield imaging signals), and typically cover large regions of cortex. Many properties of neuronal responses and behavior seem normal despite these events, though rare subjects exhibit overt generalized seizures. The underlying mechanisms of this phenomenon remain unclear, but we speculate about possible causes on the basis of diverse observations. We encourage researchers to be aware of these activity patterns while interpreting neuronal recordings from affected mouse lines and when considering which lines to study.

neuroscience↗