Age-related dysregulation of homeostatic control in neuronal microcircuits.

Neuronal homeostasis prevents hyperactivity and hypoactivity. Age-related hyperactivity suggests homeostasis may be dysregulated in later life. However, plasticity mechanisms preventing age-related hyperactivity and their efficacy in later life are unclear.

Pinpointing the locus of GABAergic vulnerability in Alzheimer's disease.

The early stages of Alzheimer's disease (AD) have been linked to microcircuit dysfunction and pathophysiological neuronal firing in several brain regions. Inhibitory GABAergic microcircuitry is a critical feature of stable neural-circuit function in the healthy brain, and its dysregulation has therefore been proposed as contributing to AD-related pathophysiology. However, exactly how the critical balance between excitatory and inhibitory microcircuitry is modified by AD pathogenesis remains unclear.

Multi-scale network imaging in a mouse model of amyloidosis.

The adult neocortex is not hard-wired but instead retains the capacity to reorganise across multiple spatial scales long into adulthood. Plastic reorganisation occurs at the level of mesoscopic sensory maps, functional neuronal assemblies and synaptic ensembles and is thought to be a critical feature of neuronal network function. Here, we describe a series of approaches that use calcium imaging to measure network reorganisation across multiple spatial scales in vivo.

Audio-visual experience strengthens multisensory assemblies in adult mouse visual cortex.

We experience the world through multiple senses simultaneously. To better understand mechanisms of multisensory processing we ask whether inputs from two senses (auditory and visual) can interact and drive plasticity in neural-circuits of the primary visual cortex (V1). Using genetically-encoded voltage and calcium indicators, we find coincident audio-visual experience modifies both the supra and subthreshold response properties of neurons in L2/3 of mouse V1.

Global brain volume reductions in a sub-chronic phencyclidine animal model for schizophrenia and their relationship to recognition memory.

Background: Cognitive deficits and structural brain changes co-occur in patients with schizophrenia. Improving our understanding of the relationship between these is important to develop improved therapeutic strategies. Back-translation of these findings into rodent models for schizophrenia offers a potential means to achieve this goal.

NMDA receptor antagonist rodent models for cognition in schizophrenia and identification of novel drug treatments, an update.

Negative and cognitive deficit symptoms in schizophrenia remain an unmet clinical need. Improved understanding of the neuro- and psychopathology of cognitive dysfunction in the illness is urgently required to enhance the development of new improved therapeutic strategies. Careful validation of animal models that mimic the behaviour and pathology of complex psychiatric disorders is an essential step towards this goal.

Towards the development of improved tests for negative symptoms of schizophrenia in a validated animal model.

Negative symptoms in schizophrenia remain an unmet clinical need. There is no licensed treatment specifically for this debilitating aspect of the disorder and effect sizes of new therapies are too small to make an impact on quality of life and function. Negative symptoms are multifactorial but often considered in terms of two domains, expressive deficit incorporating blunted affect and poverty of speech and avolition incorporating asociality and lack of drive.