Examining The Metabolic And Cognitive Deficits Caused By Insulin Resistance In The Ventral Striatum
Funder
National Health and Medical Research Council
Funding Amount
$400,372.00
Summary
Brain insulin resistance is thought to cause metabolic and cognitive deficits, but the underlying neural mechanisms remain elusive. This project addresses this gap in our knowledge by examining how brain insulin resistance disrupts the metabolic regulation of food intake and the cognitive control of actions. The outcomes will provide new insights in disorders characterised by brain insulin resistance such as obesity and dementia.
Dissecting The Role Of Cortico-striatal Circuitry On Habit Formation
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
Decisions are made based on actions and outcomes, but over time repeated actions become habits. They are no longer determined by outcomes and are dysfunctional in many disorders such as OCD, addiction and Tourette’s syndrome. How the brain changes during habit formation is not known. I will characterise the role of a specific neural circuit to determine how it influences habit development. This will improve our knowledge of normal learning processes and help us understand habitual dysfunction.
Molecular Control Of Interneuron Development And Function In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$527,828.00
Summary
This project will study the changes that occur in neurons, during normal brain maturation and in pathology. We hypothesise that early signs of brain malfunction can be detected in neurons before symptoms appear. The role of a gene will be studied during development and disease in a mouse model of autism, in order to identify the molecular and electrical signs of abnormal activity. This research will ultimately enable us to propose new strategies to treat symptoms of brain disease.
Cognitive Inflexibility And The Development Of Pathological Habits In Brain Diseases
Funder
National Health and Medical Research Council
Funding Amount
$883,946.00
Summary
Pathological habits are observed in severe mental health conditions including dementia, obsessive-compulsive disorder (OCD), schizophrenia, depression and addiction. This application aims to provide the mechanistic detail required for therapeutic targeting to restore flexible decision making in these conditions.
In pilot studies, we have found that specific genes are modulated by long-term alcohol intake in a discrete part of the brain that drives habitual behaviours. We will now repeat these studies in post-mortem brain tissue from human alcoholics and age-matched controls. In addition, we will further characterise the functional consequences of long-term alcohol intake within this specific brain region and test new approaches to reduce the urge to consume alcohol.
GPR88 As A Novel Target For Fronto-striatal Dysfunction In Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$606,966.00
Summary
GPR88 is a protein that is specifically found in the striatum, one of the main brain regions involved in schizophrenia. Studies in mice have showed that GPR88 may have a role in learning and memory; our early studies show that GPR88 controls the activity of a population of cells in the striatum. This project will determine the mechanism by which GPR88 controls the function of the striatum and how this translates into regulating brain circuitry and learning and memory relevant to schizophrenia.
New Dopaminergic Neurons In The Parkinson's Disease Striatum: Establishment Of Phenotype, Function And Origin.
Funder
National Health and Medical Research Council
Funding Amount
$156,493.00
Summary
Parkinson s disease is usually associated with loss of dopamine cells that send nerves from the substantia nigra to the striatum. However, we have found large numbers of apparently new dopaminergic cells in post mortem tissue from the striatum of 10 patients with Parkinson s disease but not in 5 age-matched controls. Our aims are firstly to determine whether these cells are indeed dopaminergic neurons by establishing their neurochemical and morphological profiles. This is required to determine w ....Parkinson s disease is usually associated with loss of dopamine cells that send nerves from the substantia nigra to the striatum. However, we have found large numbers of apparently new dopaminergic cells in post mortem tissue from the striatum of 10 patients with Parkinson s disease but not in 5 age-matched controls. Our aims are firstly to determine whether these cells are indeed dopaminergic neurons by establishing their neurochemical and morphological profiles. This is required to determine whether these apparently dopaminergic cells do indeed produce the neurotransmitter dopamine and to determine to what class of neuron they belong. The latter is important to establish whether they act locally in the striatum or extend their influence over a larger area of the brain. Secondly we shall assess their function in human and rat tissue. We shall determine whether their number is related to the severity of damage in Parkinson s disease, or whether L-DOPA therapy, which most patients receive, plays any role in their appearance. These experiments will lay the ground work to allow us to determine whether these cells are beneficial or harmful. Lastly, we shall determine where these cells come from. We shall determine whether they have always been present but have taken on a new function, or whether they are in fact new cells which have been born recently. This knowledge is essential if we are to be able to change their numbers to improve treatment of Parkinson s disease. We estimate that there are up to 66,000 of these dopaminergic cells in each striatum of patients with Parkinson s disease. This is enough to have a significant impact on the manifestation of the disease. These cells might be beneficial, allowing the brain to maintain essential functions for longer or they might be harmful playing a role in either development of Parkinson s disease itself or the harmful side effects of L-DOPA therapy.Read moreRead less
Determining Neuronal Connections Involved In Parkinson's Disease And Cocaine Addiction
Funder
National Health and Medical Research Council
Funding Amount
$343,300.00
Summary
Addictive behaviours in response to cocaine use and fine motor coordination that is affected in Parkinson's disease are both controlled by the same type of cells/neurons, i.e., dopamine neurons. However, the circuitry of these neurons varies from where they originate and the type of connections they make. By understanding the neuronal circuitry of these two circuitries in concert we will be able to gain important insight into their roles in adaptive and pathological brain function.