Two-photon calcium imaging

…The fellow uses in vivo two-photon calcium imaging in mice, behavioural assays and computational modelling to track how learning-driven changes emerge in these early circuits and how they shape perception. The post sits in the School of Biomedical Sciences, Faculty of Biological Sciences, within a Leeds neuroscience community of more than 44 research labs. Grade 7, £41,064–£48,82

…Its CaRMA imaging framework links large-scale measurements of neural activity in behaving mice to post hoc molecular identification of the same recorded neurons, combining in vivo two-photon calcium imaging with spatial transcriptomics and circuit mapping to determine how molecularly defined populations control food seeking, consumption and satiety. The Research Specialist is the lab's primary technical and scientific resource for in vivo two-photon imaging: chronic

Predicting neural activity in higher visual areas (HVAs) in mice during spatial navigation is challenging due to the complex interaction between spatial and temporal processing. One recent two-stream hypothesis for rodents proposed by Saleem (2020) suggests that form-based goals and detailed landmark signals are processed by cortical areas biased towards the central visual field, while self-motion signals are processed in the periphery. Inspired by this, we developed a deep learning model that splits visual input into two streams: a convolutional neural network (CNN) processed the central visu

Adaptive behavior is critically dependent on associative learning, where environmental cues are linked with subsequent positive or negative outcomes. At the core of this process, primary neocortical sensory areas serve as pivotal nodes, processing stimuli and distributing information to cortical and subcortical networks. Layer 5 (L5) of the cortex comprises two types of pyramidal projection neurons---intratelencephalic (IT) and extratelencephalic (ET) neurons---each with distinct downstream targets. Sensory cortex exhibits plastic changes after forming a sensory-reward association and L5 neuro

…motor learning, we performed repeated two-photon calcium imaging of the same L5 PT apic

…We employed large-scale, longitudinal two-photon calcium imaging to record activity from thousands of neurons in the CA1 region of the hippocampus while mice learned to efficiently collect rewards from two subtly different linear tracks in virtual reality. The results provide a de

The ability to reconstruct imagery represented by the brain has the potential to give us an intuitive understanding of what the brain “sees”. Reconstruction of visual input from human fMRI data has garnered significant attention in recent years. Comparatively less focus has been directed towards vision reconstruction from single-cell recordings, despite its potential to provide a more direct measure of the information represented by the brain. Here, we achieve high-quality reconstructions of videos presented to mice, from the activity of neurons in their visual cortex. With our method of video

Rapid learning confers significant advantages to animals in ecological environments. Despite the need for speed, animals appear to only slowly learn to associate rewarded actions with predictive cues. This slow learning is thought to be supported by a gradual expansion of predictive cue representation in the sensory cortex. However, evidence is growing that animals learn more rapidly than classical performance measures suggest, challenging the prevailing model of sensory cortical plasticity. Here, we investigated the relationship between learning and sensory cortical representations. We traine

…We performed two-photon calcium imaging in layer 2/3 of each area (>8,000 neurons, 19 sessions, 4 mice). Th

…In particular, two-photon holographic optogenetics now enables precise photostimulation of experimenter-specified groups of individual neurons, while simultaneous two-photon calcium imaging enables the measurement of ongoing and induced activity across the neural population. Despite the enormous space of potential photostimulation patterns and the time-consuming nature of photostimulation experiments, very little algorithmic work has been done to dete

…In a data set of two-photon calcium imaging from the visual cortex of mice (Cleppien et al., 2024+), we identified short temporal stripes of interest from the un

The hippocampus (HC) plays a pivotal role in spatial navigation and memory in the human brain. Place cells, specialised neurons residing within the hippocampus, exhibit selective firing patterns corresponding to specific spatial locations, collectively contributing to the cognitive mapping of the environment. In healthy state, the place fields in the CA1 region exhibits continuous representational turnover [1]. Spatial navigation is disrupted in Alzheimer’s Disease (AD). AD, a neurodegenerative disorder characterised by progressive cognitive decline, is associated with deficits in learning a

…complex spatiotemporal patterns of calcium activity during animal behavior. The properties, mechanisms, and physiological relevance of these patterns are still poorly understood. Here, we performed two-photon calcium imaging in cortical astrocytes expressing cyto-GCaMP6f in head-fixed mice running on a rotating platform. In each imaging frame, suprathreshold calcium activity regions (segments of spatiotemporal calcium events) were detected. We analyzed ΔF/F, total active area, mean segment area, and segment density during

The visual system consists of a hierarchy of distinct brain areas, each responsible for processing different aspects of visual features. To better understand how signals from an upstream area contribute to visual processing in the downstream area, this project will focus on a specific type of computation broadly found in the visual system: i.e., selectivity to motion direction. Many neurons in the mouse superior colliculus, a direct target of the retina, preferentially respond to stimuli moving in one direction, but not the opposite, with diverse direction preferences across populations. Such

Sleep is a physiological state often associated with a cutoff from the external world, and especially loss of conscious perception of sensory stimuli. Even though brain signatures of sleep have been studied for years, the mechanisms that prevent sensory information from reaching consciousness remain to be elucidated. Recently published findings suggest that the loss of perception experienced in anesthesia may be due to neurons population activity coding of stimuli in the cortex collapsing into the spontaneous activity subspace, therefore reflecting internally generated dynamics rather than evo

Multiple studies suggest that inhibitory neurons are involved in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). ALS and FTD are two devastating, frequently co-occurring neurodegenerative disorders. While ALS primarily affects motor neurons, causing rapid progressive paralysis and premature death, FTD affects frontal and temporal lobes, leading to severe changes in personality, behaviour, or language skills. To characterise the contribution of inhibitory neurons to these phenotypes, we generated a mouse model based on the expression of mutant Fused in Sarcoma (FUS) selec

…We employed two-photon calcium imaging to observe neuronal activity (hippocampal CA1 neurons) in behaving mice performing spatial memory tasks, capturing the dynamics of memory-related circuits. Shannon Information Theory provides a useful toolbox, applicable to the analysis of calcium imaging datasets, to assay changes in information representation and processing in brain circuits while mice are performing such cognitive tasks. In particular, the recently developed Partial Informat

…choice task and longitudinal two-photon calcium imaging, we find LHb neurons with risk-preference-selective activity re

Animals exhibit flexible and adaptive behavior in novel situations, in part relying on reward-based learning. Although the reinforcement of positive outcomes plays a central role in shaping behavior, the neural circuit mechanisms of goal-directed sensorimotor transformation remain incompletely understood. Common behavioral paradigms for studying such mechanisms are hindered by the prolonged training period needed to reach expert performance, impeding the real-time observation of plastic changes. Here, we developed a rapid whisker-based detection task where thirsty mice learn to associate a nov

The brain continuously receives a wealth of sensory information, and uses this information to guide behaviour. However, the process by which different sensory streams are integrated to form a unified percept remains poorly understood. Cortical regions dedicated to a specific sensory modality nonetheless receive input related to other modalities. The mouse auditory cortex sends numerous projections to the primary visual cortex and surrounding higher visual areas. These inputs may be crucial to the integration and binding of auditory and visual signals. Yet the exact nature of the auditory infor

Breaking the neural code requires the systematic identification and characterization of neuronal ensembles related to specific brain functions. Recent research suggests that neuronal ensembles underlie brain functions such as perception, movement, and memory processes. However, the standardization of different mathematical algorithms that allow the identification and characterization of the properties of neuronal ensembles is still lacking in the systems neuroscience field. Our work addresses this gap by introducing an open-source Graphic User Interface (GUI) designed for researchers intereste

The question of how animals make decisions and adapt their behavior in a dynamic environment – known as behavioral flexibility – is crucial for survival. It requires a balance between exploiting acquired knowledge (exploitation) and exploring potentially better alternatives (exploration). Despite its significance, the intricate computational and neural mechanisms that underpin these processes remain unclear. To address this question, we designed a task in which head-fixed mice acquire and reverse self-initiated lever-pressing preferences in the absence of instructive external cues. We combined

…which can be used in conjunction with two-photon calcium imaging to investigate changes in hippocampal network activity, including spatial and tr

…Using two-photon calcium imaging of CA3 outputs combined with simultaneous local field potential recordings, we show that the statistics of replay deviate significantly from those of experience: hig