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.
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
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.
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
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.
Problems in learning, memory and other complex mental processes are common to many brain disorders. This project will study the impact of mutations on a family of genes reported in autism and schizophrenia, on complex cognitive behaviours using novel behavioural technologies. This will not only shed fundamental insights into the specific mental processes regulated by these genes and their role in disease, but importantly provide novel targets for the development of therapies.
Disorders Of Action Control And Learning-related Plasticity In The Basal Ganglia
Funder
National Health and Medical Research Council
Funding Amount
$434,874.00
Summary
Disorders of the basal ganglia have long been known to produce severe cognitive symptoms including a deficit in the control of voluntary action. This project will assess the learning processes through which humans and other animals acquire such actions. We will systematically investigate changes in cellular plasticity associated with the acquisition of new actions to establish the role that it plays in action control under normal and pathological conditions.
How are memories stored in the brain? We know much about the brain regions involved in memory storage but we know little or nothing about how individual memories are represented and stored within those brain areas. The purpose of this project is to label and manipulate the specific subsets of brain cells that store individual memories. We will label memory-bearing cells in multiple brain regions and then ask how the connections between those cells encode learned information in the brain.
Neurogenesis In The Amygdala And Hippocampus: A Role In Learnt Fear?
Funder
National Health and Medical Research Council
Funding Amount
$780,396.00
Summary
It has long been thought that neurons are only born once and then slowly die. Learning and memory formation is thought to occur by changes in the strength of connections between living neurons. However, the hippocampus is now known to produce new neurons throughout life. We have found that neurons are also born in the adult amygdala. In this project we will study how neurogenesis affects learning and memory formation that involve the hippocampus and amygdala.