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Dopamine in the healthy and Diseased brain

 

Our laboratory focuses its attention on a population of cells in the brain that are amongst the most fascinating in the central nervous system: the neurons that produce the neurotransmitter dopamine. These neurons play a key role in a number of normal brain functions. They are also implicated in the physiopathological mechanisms of diseases such as Parkinson's, schizophrenia, attention deficit disorders and Huntington’s disease.

Some of the world’s most prescribed drugs, including antipsychotics and psychostimulants have as a primary target this neurotransmitter or its receptors. The dopamine system is also the target of drugs of abuse including cocaine and amphetamine. Within this context, our team is interested in understanding the multiple regulatory mechanisms that control the functions of these neurons in the brain, as well as their ability to release dopamine and other chemical messengers. We pay special attention to the function of the dopamine receptors as well as the basic properties of the axon terminals and dendrites of these neurons.

We are presently trying to understand how the functions of dopamine neurons are perturbed in Parkinson's disease. Our work is contributing to the discovery of new fundamental knowledge about dopamine-producing neurons. We hope that one day our discoveries will contribute to the development of new strategies to treat the various diseases that implicate this particularly challenging neuronal population.

 
 

RESEARCH ACTIVITIES

We are interested in many mechanisms regulating release of dopamine in the brain :

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EXPERIMENTAL APPROCHES

Our experiments are realized principally on mice or rat brain. We are studying neurons with many cellular and molecular biology techniques:

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Our team efforts are focussed on the Mechanisms regulating neurotransmitter release by dopamine neurons and on the dysfunctions of dopamine neurons in disease :

Modulation of dopamine release by midbrain dopamine neurons.

Development of the axonal arbour of dopamine neurons.

Connectivity of dopamine neurons.

Dopamine/glutamate cotransmission.

Mechanism of somatodendritic dopamine release.

Origin of selective vulnerability in Parkinson's disease.

Mitochondrial dysfunction in Parkinson's disease.

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Our work is performed using mice as a model. We take advantage of a range of classical and modern cellular and molecular biology techniques:

 

Electrophysiology (patch clamp) and optogenetics.

Cyclic voltammetry (to measure dopamine release).

Digital fluorescence imaging.

Confocal imaging.

Cell culture (mainly primary neuronal cultures).

Immunofluorescence and western blotting.

mRNA measurements using RT-PCR.

Cellular bioenergetics (using a Seahorse bioanalyzer).

Acute transfection (mainly using viruses).

Brain slice preparations.

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Parkinson's disease and drug abuse: 
why study dopamine?

The Trudeau laboratory is interested in the chemical messenger of the brain called
"dopamine". But why should we be interested in messengers or "neurotransmitters" of this type? The main reason is that many diseases such as Parkinson's disease, schizophrenia and drug abuse are accompagnied by pertubations of dopamine production and release in the brain. In order to discover new strategies to treat such disorders, it is essential to know more about how the cells that produce dopamine in the brain function.

Parkinson's disease

Parkinson's disease is a severe degenerative brain disease that is presently impossible to cure. The most visible symptoms of the disease are those that affect movement, including resting tremor, slowing of movement and freezing episodes. These symptoms are caused in great part by the loss of a subgroup od dopamine-producing neurons in the brain. The disease is also incapacitating because of the multiple other non-motor symptoms, including loss of the sens of smell, sleep disturbances and peripheral nervous system impairments. The exact causes of Parkinson's disease are still the subject of intense investigation. However, dysfunctions of a number of basic cellular processes including energy production by mitochondria, elimination of pathological protein aggregates and excessive production of reactive oxygen species appears to be at the heart of the disease. The medications presently available for this disorder are essentially symptomatic, but unfortunately do not slow down the gradual loss of dopamine-producing neurons with age.

Drug dependence

Drug dependence is characterized by the compulsive seeking and consumption that often develops following repeated exposures to such molecules. The development of a dependence depends on multiple factors including the type of drug, the route of drug administration, the frequency of drug use, stress etc.. Genetic predisposing factors are also probably involved. Although different drugs (cocaine, alcohol, nicotine, heroin etc.) have different physiological and psychological effects, most of them act, one way or another, by influencing the release of dopamine in the brain. Drugs seem to leave a long-lasting “trace” in the brain, something like a form of long-term memory. Very little if any pharmacological strategies are presently available to treat the vicious cycle of compulsive drug use.

Research is our hope

The research that is presently performed in the laboratory of Dr. Trudeau aims to provide a better understanding of the fine mechanisms that control dopamine release and the origin of the vulnerability of dopamine neurons. Our research is performed using mice as a research subject, a species that has a brain structure that is surprizingly similar to that of humans. Our work involves mostly basic, fundamental research, but the hope is that such work will lead to the identification of new strategies to identify targets for thetreatment of diseases like Parkinson's disease, schizophrenia and drug abuse.

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If you are interested to join our team as a graduate student in the pharmacology or neuroscience program, or as a postdoctoral fellow, please send your CV and most recent transcript by email to Dr. Trudeau. Please also note that although the lab operates in both English and French, graduate programs at the Université de Montréal require a minimal knowledge of French.

 

 

Dr. Louis-Eric Trudeau

e-mail

Department of pharmacology and physiology

Department of neurosciences

Office: room S-401 - Roger-Gaudry building

Laboratory: room S-405 -Roger-Gaudry building

 

Tel.: (514) 343-5692 (office) or 343-6111 extension 3821 (Lab) 
Fax: (514) 343-2291

 

Postal address:

Department of pharmacology and physiology

Université de Montréal
C.P. 6128 - Succursale Centre-ville
Montréal - Québec,  H3C 3J7

 

Address for deliveries:

Department of pharmacology and physiology

Room S-405, Roger-Gaudry building

Université de Montréal
2900 Boulevard Édouard-Montpetit

Montréal, Québec, H3T 1J4

 

Useful links

Department of pharmacology and physiology

Department of neurosciences

Research Group on the Central Nervous System

Society for Neuroscience

Canadian Association for Neuroscience

Universite de Montreal web site: useful information for prospective students