cortical circuits group
The research in our lab aims to understand the biological implementation of information processing in cortical circuits, with a particular focus of sensory circuits and associated brain regions. We use a range of in vivo imaging approaches to record and manipulate neural activity at single cell and sub-cellular resolution in order to shed light on 1) how specific patterns of connectivity between neurons gives rise to computation and information processing, and 2) the rules and mechanisms through which these complex patterns of connectivity are initially 'wired' during development. We are additionally involved in diverse collaborative projects using the same powerful in vivo imaging methods to study questions unrelated to cortical computation including the role of astrocytes in epileptic seizure initiation (Crunelli lab, UK), abnormal microglia cytoskeletal remodelling in Alzheimer's disease (Taylor lab, UK) and hemodynamic coupling of blood vessel dilation to neural activity (Murphy lab, UK).
Currently we have a particular interest in:
The connectivity of cortical feedback circuits which may allow flexible sensory processing depending upon current context or behaviour
The rules which determine how neurons in cortical circuits 'decide' which other neurons to listen and speak to, and how this is driven by experience of the environment
Impairments in predictive or top-down cortical circuits as an explanation of symptoms of psychosis
We use a range of state of the art in vivo brain imaging approaches to visualise neural activity and structure in awake behaving mice. The main technique we use is in vivo two-photon imaging together with genetically encoded neural activity indicators (such as GCaMP). This allows visualisation of neural activity at spatial scales ranging from populations, to single neurons, axons, dendrites and individual spines. As well as this we use a lower resolution approach known as intrinsic signal imaging to perform in vivo mapping of the location of gross brain regions.
We combine these neural activity recording methods with sensory stimulation, visually guided detection behaviours, eye position tracking and simple virtual reality environments in order to visualise cortical circuits while they are in action processing information and guiding action.
recruitment of topdown circuits from ACC to V1 during visually guided behaviour
The cingulate cortex (Cg) provides long-range retinotopically specific top-down input to the primary visual cortex (V1) in mice. Previous studies have argued that this circuit may serve as a mechanism of selective attention, as optogenetic stimulation of this projection enhances visual responses and improves visual discrimination. Other work has argued for a role of this projection in relaying predictive motor signals to sensory cortex. In this study we are characterising the endogenous recruitment of this circuit during visually guided behaviour. Specifically, we are using two-photon microscopy to longitudinally image activity of GCaMP6s labelled axons originating from Cg in layer 1 of V1 while animals performed a Go/Nogo visual discrimination task.
Top-Down Suppression of Sensory Cortex in an NMDAR Hypofunction Model of Psychosis
Conceptual and computational models have suggested that perceptual disturbances in psychosis, such as hallucinations, may arise due to a disruption in the balance between bottom-up (i.e. sensory) and top-down (i.e. from higher brain areas) information streams in sensory cortex. In this project we are using in vivo 2-photon imaging to measure frontal top-down signals from the anterior cingulate cortex (ACC) and their influence on activity of the primary visual cortex (V1) in mice in a pharmacological model of psychosis. Our findings so far are consistent with a model in which perceptual disturbances in psychosis are caused in part by aberrant top-down frontal cortex activity which suppresses the transmission of sensory signals through early sensory areas.
the rules and development of the targeting of visual feedback signals
Higher visual areas, such as the lateral medial visual area in rodents, send dense axonal projections to lower levels of the processing hierarchy. The purpose or function of these feedback signals remains unclear, but they have been suggested to provide a substrate for a form of predictive processing (Marques et al. 2018). In this study we are examining 1) the relationship between the functional properties of LM>V1 axons and the neurons they target in V1 in the awake brain, and 2) the manner in which this feedback circuit forms after eye opening, testing the hypothesis that this putative predictive circuit recapitulates visual experience.
encoding of visual cues in
the mouse retrosplenial cortex
The rodent retrosplenial cortex functions as an integrative hub for sensory and motor signals, serving roles in both navigation and memory. While retrosplenial cortex (RSC) is reciprocally connected with the sensory cortex, the form in which sensory information is represented in the retrosplenial cortex and how it interacts with behavioural state is unclear. Here, we used 2-photon cellular imaging of neural activity of putative excitatory (CaMKII expressing) and inhibitory (parvalbumin expressing) neurons to measure visual and running evoked activity in RSC and compare it to primary visual cortex (V1). We found that while stimulus positional information was preserved between V1 and RSC, and even organised topographically, responses were more invariant with respect to higher order feature such as stimulus orientation.