I am a molecular physiologist investigating the structure and function of the inhibitory neurotransmitter glycine receptor (GlyR) and GABA type- A receptor (GABAAR) chloride channels. We are interested in understanding how these receptors open and close
I am a neuroscientist- neuropharmacologist determining molecular, cellular, synaptic and behavioural mechanisms of opioid addiction and persistent pain states.
I am a clinical scientist translating basic science findings into clinical science questions and answers that impart better understanding and management of pain and painful disease.
Speech and chewing are accomplished automatically by the jaw muscles which have both the power to chew meat and even bone, and the precision to make extremely fine adjustments to the shape of the mouth that enable speech. The brain needs constant inputs from sensory receptors in and around the mouth to control these muscles. We will investigate how these sensory mechanisms automatically fine-tune the activity of the jaw muscles and the mechanisms that keep the jaw in its normal position when the ....Speech and chewing are accomplished automatically by the jaw muscles which have both the power to chew meat and even bone, and the precision to make extremely fine adjustments to the shape of the mouth that enable speech. The brain needs constant inputs from sensory receptors in and around the mouth to control these muscles. We will investigate how these sensory mechanisms automatically fine-tune the activity of the jaw muscles and the mechanisms that keep the jaw in its normal position when the subject is sitting quietly, or when the head is moving up and down during running. This normal rest position of the jaw is a vital point of reference for dentists who are making false teeth and for surgeons who are restoring damaged faces, but it is not known what mechanisms are responsible for it. Anyone who has experienced a sore tooth or sore jaw muscles will know that pain adversely affects normal chewing. A common symptom is limitation of jaw movements. We will determine how pain affects the control of jaw muscles. This is important for people with chronic facial pain from arthritis of the jaw joint or from grinding their teeth while they are asleep. Even if it is not possible to eliminate their pain, we hope to suggest approaches which will alleviate its effects. Another part of our study involves a computer model of the chewing system. Computer models enable scientists to examine the effect of various interventions such as surgery or orthodontics on a model before these are tried on humans. It is also possible to use such a virtual patient to answer important functional questions that cannot be examined in humans because the methods are unavailable, or because the procedures would be ethically unacceptable. The current version of the computer model is quite sophisticated anatomically, but lacks important information on the control systems that activate the muscles. We will collaborate with the developers of the model by providing this information.Read moreRead less
Neurochemical And Metabolomic Studies Of The Cortical GABAergic System
Funder
National Health and Medical Research Council
Funding Amount
$282,559.00
Summary
This work will use targeted neuropharmacology, systems analysis and multivariate statistics to provide a unique perspective on detailed aspects of the organization and function of the GABAergic system in the brain, as well as the mode of action of the drug of abuse GHB. This will have broad benefits for a wide range of disorders, including sleep disorders, pain and epilepsy as well as providing clearer targets for drug development.
Synaptic Integration And Plasticity In The Rat Piriform Cortex
Funder
National Health and Medical Research Council
Funding Amount
$250,500.00
Summary
The human cerebral cortex is the pinnacle of evolution. It is the most complex structure known, responsible for all of those skills - like language and reasoning - that make our species so remarkable. It is also a major site of many brain diseases, like schizophrenia and epilepsy. An understanding of how the cerebral cortex works would be a remarkable achievement, of immeasurable benefit to human health. How can one go about studying such a complex structure? The strategy taken in this project i ....The human cerebral cortex is the pinnacle of evolution. It is the most complex structure known, responsible for all of those skills - like language and reasoning - that make our species so remarkable. It is also a major site of many brain diseases, like schizophrenia and epilepsy. An understanding of how the cerebral cortex works would be a remarkable achievement, of immeasurable benefit to human health. How can one go about studying such a complex structure? The strategy taken in this project is to begin by studying one of the simplest regions of the cerebral cortex, the olfactory (or piriform) cortex. The olfactory cortex is an evolutionarily ancient region of cortex, with a simpler architecture than other cortical regions. Its task is to process the sense of smell, a primitive sense that is more elaborated in lower animals than in humans. The broad goal of our research is to understand, by studying the olfactory cortex of rats, how olfactory processing occurs at the level of nerve cells (neurons). We will use a number of powerful techniques - including microelectrode recording and laser microscopy - to measure the electrical properties of individual neurons. We will also study the synaptic connections between neurons, and how these connections change following memory-inducing stimuli. It is hoped that this work will shed light on how the healthy cortex is able to process and store information, and how brain diseases cause these functions to deteriorate.Read moreRead less
Synaptic Transmission In The Mammalian Central Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$460,500.00
Summary
In order to properly understand the complex functions of the brain and the abnormalities underlying neurological disorders, we must understand how individual neurons communicate with each other. Communication occurs at specialized contacts, or synapses. An individual neuron may receive tens of thousands of synaptic contacts from hundreds or thousands of other neurons. Despite intensive investigation, the processes which regulate synaptic strength between central neurons are poorly understood. Th ....In order to properly understand the complex functions of the brain and the abnormalities underlying neurological disorders, we must understand how individual neurons communicate with each other. Communication occurs at specialized contacts, or synapses. An individual neuron may receive tens of thousands of synaptic contacts from hundreds or thousands of other neurons. Despite intensive investigation, the processes which regulate synaptic strength between central neurons are poorly understood. The overall aim of this proposal is to understand the basic mechanisms underlying synaptic transmission at excitatory and inhibitory synaptic connections in the mammalian brain. We will investigate specific synaptic connections in the central pathways of the auditory system, because our previous studies have demonstrated a number of key technical advantages in studying these synapses. We will use electrophysiological recording from synaptic terminals and neurons in isolated living slices of the brainstem of mice. We will use imaging techniques and electron-microscopy to examine the structural details of synaptic connections, as structure is thought to play a major role in determining the strength of synaptic transmission. We will also study the structural and functional properties of auditory synaptic connections in congenitally deaf animals. Our recent study comparing normal and congenitally deaf mice has already revealed significant differences. Our results will provide important insights in the regulation of synaptic strength in the central nervous system, and into the regulation of synaptic transmission at central synapses which have developed under conditions of abnormal sensory activation.Read moreRead less
The Contributions Of Different Sources Of Calcium To The Induction Of Long Term Potentiation
Funder
National Health and Medical Research Council
Funding Amount
$267,750.00
Summary
When we make memories, we alter the strength of synaptic connections between nerve cells.These changes are particularly marked in the hippopcampus ; a region of the brain involved in the formation of memories. The strength of a synaptic connection is altered if it activates a neurone sufficiently to cause a rise in the level of calcium ions. Calcium can be derived from several sources within the neurone. This project aims to assess the relative importance of these different sources of calcium in ....When we make memories, we alter the strength of synaptic connections between nerve cells.These changes are particularly marked in the hippopcampus ; a region of the brain involved in the formation of memories. The strength of a synaptic connection is altered if it activates a neurone sufficiently to cause a rise in the level of calcium ions. Calcium can be derived from several sources within the neurone. This project aims to assess the relative importance of these different sources of calcium in inducing increases in synaptic strength.Read moreRead less