Brain Plasticity Following Changes In Sensory Input
Funder
National Health and Medical Research Council
Funding Amount
$312,576.00
Summary
The research proposed here will investigate the mechanisms our brains use to adapt to changes in sensory input, as occurs following blindness, deafness, nerve damage or loss of a limb. The information gathered will help develop treatments for diseases associated with sensory loss, as well as those associated with deficits in our ability to learn and remember, such as Alzheimer's disease.
The Role Of Action Potentials In Local Calcium Signalling And Induction Of Different Forms Of LTP
Funder
National Health and Medical Research Council
Funding Amount
$330,691.00
Summary
Our understanding of how the brain learns and remembers things is still limited. There is good evidence that changing the strength of the connections (synapses) between brain cells (neurons) can allow information to be stored. One type of synaptic change is called long-term potentiaton (LTP), which is a long-lasting increase in the efficacy of communication between neurons. Recently, I have described 3 different forms of LTP in a region of the brain that is known to be important for learning and ....Our understanding of how the brain learns and remembers things is still limited. There is good evidence that changing the strength of the connections (synapses) between brain cells (neurons) can allow information to be stored. One type of synaptic change is called long-term potentiaton (LTP), which is a long-lasting increase in the efficacy of communication between neurons. Recently, I have described 3 different forms of LTP in a region of the brain that is known to be important for learning and memory. These forms of LTP have different persistence characteristics - LTP 1 is relatively short-lasting, LTP 2 is of intermediate duration, and LTP 3 is very long-lasting and perhaps even permanent. Each form of LTP is selectively triggered by an increase in calcium in a different part of the neuron. In the present study, I will investigate the relationships between electrical activity in different parts of the neuron in order to define the 'rules' for triggering each form of LTP. This information is important for future studies into the specific role played by each form of LTP in learning and memory processing in the brain. A better understanding of the relationship between LTP and learning and memory will assist in developing effective treatment strategies for disorders of memory, including Alzheimer s disease, addictive bahaviour, and learning disorders.Read moreRead less
Sleep Disordered Breathing And Neurocognitive Function In Children Post-adenotonsillectomy: Three Year Follow-up
Funder
National Health and Medical Research Council
Funding Amount
$266,536.00
Summary
Snoring is very common and affects at least 10% of children, or an estimated 0.25 million children in Australia. It is associated with deficits in a wide range of neurocognitive areas including intelligence, memory, reasoning, learning and behaviour. We have recently studied a group of 53 snoring children both before and six months after removal of their tonsils and adenoids, to treat suspected upper airway obstruction associated with their snoring. We found that prior to surgery, intelligence, ....Snoring is very common and affects at least 10% of children, or an estimated 0.25 million children in Australia. It is associated with deficits in a wide range of neurocognitive areas including intelligence, memory, reasoning, learning and behaviour. We have recently studied a group of 53 snoring children both before and six months after removal of their tonsils and adenoids, to treat suspected upper airway obstruction associated with their snoring. We found that prior to surgery, intelligence, memory, reasoning, language and behaviour were significantly reduced, by up to 10% compared to 53 non-snoring control children matched by age, gender, social class and area of residence. To our great surprise, at six months after surgery we found that although sleep and behaviour improves, intelligence, memory, reasoning and language development do not. We now wish to study these same children at 3 years after tonsils and adenoids removal, as we believe that if the deficits that we described at 6 months are still present, they are likely now to be permanent. Given the degree of deficit that we have found in snoring compared to non-snoring children, even 6 months after the snoring group of children have been treated, if still present at 3 years post-surgery then it is likely that these deficits will affect the children's future learning potential and academic success. In turn, this would suggest that early identification and treatment of sleep-related upper airway obstruction is critical in preventing long-term deficits in children's daytime functioning and behaviour.Read moreRead less
The Extinction Of Conditioned Fear And Its Implications For Cue Exposure Therapy
Funder
National Health and Medical Research Council
Funding Amount
$322,430.00
Summary
This project studies extinction of Pavlovian conditioned fear reactions in rats. Extinction of these reactions is an animal model for exposure therapy used in the treatment of anxiety disorders in people. In exposure therapy, the patient, aided by the clinician, confronts trauma-related cues in the absence of any overt danger. The intention of this therapy is to reduce the ability of the trauma-related cues to provoke the fear reactions that are undermining the patient's quality of life. In Pavl ....This project studies extinction of Pavlovian conditioned fear reactions in rats. Extinction of these reactions is an animal model for exposure therapy used in the treatment of anxiety disorders in people. In exposure therapy, the patient, aided by the clinician, confronts trauma-related cues in the absence of any overt danger. The intention of this therapy is to reduce the ability of the trauma-related cues to provoke the fear reactions that are undermining the patient's quality of life. In Pavlovian conditioning, subjects (typically rats) are exposed to a signaling relation between an initially neutral stimulus (e.g., a noise) and a feared outcome (e.g., foot shock). When later repeatedly exposed to the initially neutral but now feared stimulus (the noise) in the absence of the feared outcome, the fear reactions it acquired progressively decline until eventually it fails to elicit any such reactions. The fear reactions are said to have been extinguished. There has been significant progress in understanding the psychological processes and neural mechanisms underlying the acquisition of fear reactions, but much less is known about the processes and mechanisms underlying the extinction of these reactions. The project has two general objectives. The first is to determine the conditions of extinction training that promote long-term loss of fear reactions. The second objective is to determine how the brain controls this extinction of learned fear. Achieving these aims will be significant for two reasons. First, it will contribute to understanding the mechanisms by which animals (including people) learn to adjust their behaviour to bring it into line with the current relations that exist between events in the world. Second, it will provide important information about how such adjustment is facilitated or impaired across extinction training and, thereby, contribute towards understanding both the successes and failures of cue exposure therapy for fear-related disorders.Read moreRead less
The amygdala is an area of the brain that is involved in assigning emotional content to sensory information. Disorders of the amygdala lead to a variety of anxiety-related mental disorders such as panic attacks and post-traumatic stress. This grant will study how the NMDA receptor, which plays a central role in memory formation, works in the amygdala. We will determine the functional role of this receptor in the amygdala and how it may be modified by experience.
Mechanisms And Consequences Of Cholinergic Signaling In Neocortical Pyramidal Neurons
Funder
National Health and Medical Research Council
Funding Amount
$258,000.00
Summary
Dementia, including Alzheimer s Disease, represents the second highest non-fatal disease burden in Australia. Modern theories suggest that cognitive deficits associated with disorders such as Alzheimer s Disease result in part from impairment of the action of the neurotransmitter acetylcholine. Despite the obvious importance of acetylcholine in brain function, there is currently a lack of basic knowledge regarding how this chemical works at the cellular level. We have recently discovered that ac ....Dementia, including Alzheimer s Disease, represents the second highest non-fatal disease burden in Australia. Modern theories suggest that cognitive deficits associated with disorders such as Alzheimer s Disease result in part from impairment of the action of the neurotransmitter acetylcholine. Despite the obvious importance of acetylcholine in brain function, there is currently a lack of basic knowledge regarding how this chemical works at the cellular level. We have recently discovered that acetylcholine produces opposing phasic and tonic actions on the excitability of brain cells in the cortex. The data collected in this study will reveal the receptor type, intracellular signalling pathways, and ionic mechanisms through which acetylcholine influences information processing in the brain. Together, these results will provide a framework for understanding the biological basis by which acetylcholine influences cognitive function. This new knowledge will in turn increase our understanding of why dysfunction of this important neurotransmitter system leads to the functional deficits observed in Alzheimer s Disease and other forms of dementia, and will hopefully suggest new targets for therapeutic intervention.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
The Structural Basis Of Direction Selectivity In The Retina
Funder
National Health and Medical Research Council
Funding Amount
$401,705.00
Summary
The retina is part of the central nervous system and there are almost one hundred types of retinal neurons which process visual information before it is passed up the optic nerve to the brain. This project examines how some of these neurons are wired together to form a simple neuronal circuit that detects the direction of a moving object. The elucidation of the cellular mechanisms of direction selectivity will provide an important paradigm of complex processing by simple neuronal circuits, with ....The retina is part of the central nervous system and there are almost one hundred types of retinal neurons which process visual information before it is passed up the optic nerve to the brain. This project examines how some of these neurons are wired together to form a simple neuronal circuit that detects the direction of a moving object. The elucidation of the cellular mechanisms of direction selectivity will provide an important paradigm of complex processing by simple neuronal circuits, with direct relevance to information processing in other parts of the central nervous system. In particular, the project may provide strong evidence for two neuronal strategies that may be of general significance. First, information may be processed at a very local level, which would greatly increase the computational power of a single neuron. Second, neurons may make selective contact with only some processes of an input neuron, which would require novel mechanisms for producing the necessary specificity.Read moreRead less
Drug addiction imposes significant burdens on individual drug users, their families, and communities. This project uses an animal model to identify the brain regions and pathways which mediate extinction of drug seeking and therefore contribute to long-term abstinence from drug-seeking. The work will show how the brain inhibits drug-seeking and will contribute to the important goal of identifying new approaches to preventing relapse to drug-seeking.
Insulin-regulated Aminopeptidase, Glucose And Memory
Funder
National Health and Medical Research Council
Funding Amount
$555,693.00
Summary
We have previously shown that inhibitors of IRAP improve performance in memory tasks in normal and memory impaired animals and are currently developing new treatments for memory loss using IRAP as a target. In this study, we will investigate the physiological roles of IRAP and its association with intracellular proteins. The knowledge obtained will provide insights of how the brain process memory and confirm the suitability of IRAP inhibitors as drugs for treating memory deficits.