Exercise Reverses Cognitive Decline In Aged Animals By Growth Hormone Stimulation Of Neurogenesis In The Hippocampus
Funder
National Health and Medical Research Council
Funding Amount
$696,409.00
Summary
The production of new neurons in the hippocampus plays a critical role in learning and memory. With increasing age, this production slows and is associated with cognitive decline. However the stem cells that make new neurons are still present, and we have discovered that exercise activates these cells, leading to renewed neuron production and reversal of cognitive decline. We will explore how this process is regulated in order to develop strategies to reduce cognitive decline in humans.
Thalamocortical Neural Circuits In Higher Order Cognitive And Sensory Processing
Funder
National Health and Medical Research Council
Funding Amount
$370,860.00
Summary
Schizophrenia, depression and dementia are devastating disorders with problems in thinking and sensory perception, but the neural circuits causing these symptoms are not known. I will use new optical and genetic tools in mice to identify the cortical and subcortical circuits required for complex touchscreen tasks, the same tasks to assess patients. Identification of neural circuits that underlie clinical symptoms will increase our understanding of these disorders and improve treatments.
Neuronal Linking Of Attention, Perception And Action
Funder
National Health and Medical Research Council
Funding Amount
$586,469.00
Summary
We are able to perceive and interact with the environment around us primarily because a filter of attention selects just the objects or features of relevance in the world and helps to make appropriate motor responses. This project will study how attentional networks of the brain operate to link our perception and action. An understanding of this process is fundamental to revealing the underlying pathology in many neurological conditions where attention is impaired.
Ascending Control Of Behavioural State And Cognition - Role Of Nucleus Incertus And Relaxin-3 Transmission
Funder
National Health and Medical Research Council
Funding Amount
$540,356.00
Summary
Mental illness and dementia are significant social and economic burdens worldwide and knowledge of their underlying causes and more effective therapies are required. Our research aims to use pre-clinical models to characterize a little studied neuronal network implicated in control of brain theta rhythm activity, which could lead to improved treatment of neuropsychiatric diseases such as anxiety and depression, and degenerative cognitive decline.
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
Gene-environment Interactions And Synaptic Plasticity In The Developing And Dysfunctional Cerebral Cortex
Funder
National Health and Medical Research Council
Funding Amount
$526,026.00
Summary
The cerebral cortex contains many billions of neurons, which are interconnected by trillions of synapses, to form networks underlying our most complex brain functions. It is only after birth, with environmental stimulation, that diverse brain functions begin to emerge. We are interested in the mechanisms whereby the genetic programme regulating maturation of the cerebral cortex is sculpted by interaction with the environment, as well as ongoing gene-environment interactions and mechanisms of pla ....The cerebral cortex contains many billions of neurons, which are interconnected by trillions of synapses, to form networks underlying our most complex brain functions. It is only after birth, with environmental stimulation, that diverse brain functions begin to emerge. We are interested in the mechanisms whereby the genetic programme regulating maturation of the cerebral cortex is sculpted by interaction with the environment, as well as ongoing gene-environment interactions and mechanisms of plasticity in postnatal brain. Many brain disorders, including schizophrenia, autism, epilepsy, Alzheimer's and Huntington's disease, involve abnormal development or function of the cerebral cortex. Our group has recently demonstrated that onset and progression of Huntington's disease, previously considered the epitome of genetic determinism, can be modulated by environmental factors, suggesting that all brain disorders must involve gene-environment interactions. In this project we are focusing on a specific molecular pathway which processes information from the environment and induces experience-dependent changes in the structure and function of neurons in cerebral cortex. We know that the molecular pathway we are examining has been linked to schizophrenia, a disorder of brain development, and we are attempting to understand how disruption of these molecular pathways can lead to the abnormal brain development and plasticity seen in this disease. We hope to discover neurobiological mechanisms which provide integrative understanding at the level of molecules, networks of neurons, and behaviour, in mouse models of brain disorders with disruption of specific genes, receiving different types of environmental stimulation. Analysing normal mice in this project will also provide new information on mechanisms of plasticity in the healthy cerebral cortex, that may underlie higher brain functions such as learning, which occurs throughout postnatal life, and memory.Read moreRead less
Optimising Exercise Prescription For Brain Health In Older Adults At Risk Of Dementia
Funder
National Health and Medical Research Council
Funding Amount
$594,123.00
Summary
To reduce dementia burdens in the community, cost effective and targeted early regenerative strategies are critical. Engaging in frequent aerobic exercise is one strategy that can delay the onset and slow the progression of dementia. However, prescription is limited by an incomplete understanding of how exercise positively influences brain health. Here I will investigate the influence of current exercise levels, intensity and exercise environment on brain health in adults at risk of dementia.
IRAP inhibitors are currently being developed as a new class of drugs for treating dementia and other forms of memory deficits. However, there are still gaps in our knowledge about how these drugs act to improve memory. The experiments outlined in this proposal will provide important insights into the drug action in different mouse models of memory deficit.
Epigenetic mechanisms regulating sex differences in fear-related learning and memory. Anxiety disorders represent an enormous burden on society and are associated with premature aging and infertility in men and women. Evidence also indicates that parental anxiety affects child development. Given that fear-related learning has an important influence on emotional health which, in turn, affects lifestyle and the aging process, an understanding of the neural mechanisms mediating sex differences in ....Epigenetic mechanisms regulating sex differences in fear-related learning and memory. Anxiety disorders represent an enormous burden on society and are associated with premature aging and infertility in men and women. Evidence also indicates that parental anxiety affects child development. Given that fear-related learning has an important influence on emotional health which, in turn, affects lifestyle and the aging process, an understanding of the neural mechanisms mediating sex differences in fear learning will enhance our ability to develop better therapeutic approaches for treating anxiety and preventing relapse, potentially through a gender-specific approach. The studies outlined in this proposal will have implications for promoting and maintaining good health.Read moreRead less