Projects -  Diseases -  Processes -  Techniques -  Equipment -  Collaborations -  Group members -  Publications & further information

Research

Research in my lab focuses on a wide range of projects from molecular mechanisms of synaptic plasticity in the brain to pathological aspects of the central nervous system (CNS) including Alzheimer's disease. This is achieved through electrophysiological recordings, calcium imaging, molecular biology, cell culture, gene transfection, immunocytochemical techniques and MRI-brain imaging.

The plastic nature of synapses means that long-term potentiation (LTP, a prolonged increase in synaptic transmission) and long-term depression (LTD, a long-lasting depression of synaptic transmission) can be induced.

Using brain slice electrophysiology and calcium imaging techniques, our findings from the perirhinal cortex have suggested a new form of LTD in which G-protein coupled metabotropic glutamate receptors (mGluRs) have an important role. These findings have led to a greater understanding of mechanisms that regulate mGluRs and the ways in which mGluRs interact with other receptors. Our group is also investigating the molecular roles of postsynaptic calcium sensors and caspase-cascades in hippocampal and perirhinal LTP.

Synaptic plasticity in human embryonic stem cell-derived neurons: One of the major questions at the present time is whether the CNS can be repaired following head injury and/or degenerative disorders. Head injury or aging frequently leads to disorders which are associated with substantial levels of cognitive disability.

Recent studies have suggested that the generation of neurons and glia from multipotential stem cells represents a promising strategy for CNS repair.

Our studies have established a protocol to differentiate neurons from human embryonic stem (hES) cells in brain slices. We intend to investigate the functional synaptic properties and synapse formation in human ES cell-derived neurons.

Stress is defined as any condition that seriously perturbs physiological and psychological homeostasis, ranging from anxiety to posttraumatic stress disorder: There may be evolutionary advantages in learning to cope with stress because of the unpredictable nature of life. However, excessive or prolonged stress can lead to physical and emotional exhaustion, including mental illness and memory disorders.

Corticosterone, which is secreted during stress, has been implicated in beta-amyloid protein deposition. My group investigates the mechanism by which stress triggers beta-amyloid protein deposition in the brain, which causes Alzheimer's disease.

Stress-related hormones in excitatory synaptic transmission: Stress has been shown to have a profound effect on cognitive functioning, synaptic plasticity, dendritic morphology and neurogenesis within the CNS. We are studying the action of stress hormone corticosterone in excitatory and inhibitory synaptic transmission in the hippocampus and the perirhinal cortex.

Aging and stress-related decline of recognition memory in humans: Recognition memory requires judgement concerning prior occurrence. For example, if you see a person in the street you might recollect information such as their name, or where you previously met. In the normal person, the ability to discriminate between what is novel and what is familiar, or what has occurred recently is an effortless task. Such judgements of prior occurrence are important for everyday human life. Loss of recognition memory is a major symptom of amnesia and early Alzheimer's disease.

In our lab, we are investigating the role of the perirhinal cortex in visual recognition memory during normal aging and stress. We are also characterising the relationship between circadian-mediated stress and cognition and assessing whether the correlation between stress and cognitive deficit is due to neurological insults such as brain atrophy.

Top

Projects -  Diseases -  Processes -  Techniques -  Equipment -  Collaborations -  Group members -  Publications & further information

Top