ANATOMICAL
AND FUNCTIONAL ORGANIZATION OF BASAL GANGLIA IN PRIMATES
Our research program aims at determining the major characteristics of the anatomical and functional organization of basal ganglia (BG) in primates, both in normal and pathological states. The BG lies at the base of the cerebral hemispheres and is known to play a crucial role in the control of motor and psychoaffective behavior.
SINGLE-CELL NEUROANATOMIC STUDIES
Our recent neuroanatomical studies have underlined various shortcomings regarding the current model of the BG. Our goal is to gather novel information in respect to the way neural information is conveyed and integrated in the BG so as to test the validity of the current model. We are using a new method of injecting anterograde tracers into single neurons so as to visualize their entire architecture which includes the axonal arborization.
CHEMICAL ANATOMY OF THE HUMAN STRIATUM
Our goal is to increase our understanding of the chemical anatomy of the normal human striatum and to document variations in cases of Huntington's disease (HD). Immunohistochemistry and in situ hybridization procedures are used on human post-mortem tissue from our own brain bank. One of the major questions is why striatal interneurons are selectively spared, whereas striatal projection neurons are specifically affected in HD. Double-labeling studies are utilized to reveal the types of glutamate receptors expressed by each class of striatal neurons and to determine the levels of the enzyme suproxide dismutase and the protein « Huntingtin » expressions. We hope to demonstrate that all striatal interneurons are spared in HD and that the primary pathology in this neurodegenerative disease is not located in the striatum itself but rather in striatal target structures.
ANTI-APOPTOTIQUE PROTEINS
We hope to determine if anti-apoptotic proteins (athanoproteins) are involved in neuronal protection and in postnatal neurogenesis in primates, and humans. We have recently demonstrated that the athanoproteins Bcl-2 continues to be expressed particularly in limbic structures of the adult monkey brain. There is also a strong Bcl-2 expression in the subventricular zone (SVZ), which gives rise to the rostral migratory pathway to the olfactory bulb in rodents. Our data suggest that Bcl-2 could protect neurons against apoptosis encountered in neurodegenerative diseases and act as a marker of neuronal immaturity. Our studies aim at comparing the localization and levels of expression of several athanoproteins in the brain of humans and monkeys under normal conditions and in cases of neurodegenerative diseases. We are also currently using several molecular markers to investigate the mechanisms of proliferation, migration, differentiation and cell death involved in the function of the SVZ and its efferent migratory pathways in postnatal primates.
These projects are supported by the Medical Research Council of Canada, the Canada Council for the Arts and the Parkinson Foundation of Canada.
Charara A, Smith Y, Parent A (1996) Glutamatergic inputs from the pedunculopontine nucleus to midbrain dopaminergic neurons in primates: PHA-L anterograde labeling with post-embedding glutamate and GABA immunohistochemistry. J Comp Neurol 364: 254-266.
Cicchetti F, Parent A (1996) Striatal interneurons in Huntington's disease: Selective increase in the density of medium-sized calretinin-immunoreactive neurons. Movement Disorders 11: 619-626.
Cicchetti F, Lacroix, S, Beach, TG, Parent A (1998) Calretinin gene expression in the human thalamus. Mol Brain Res 54: 1-12.
Bernier PJ, Parent A (1998) Bcl-2 protein as a marker of neuronal immaturity in postnatal primate brain. J Neurosci 18: 2486-2497.
Parent A. (1998) The brain in evolution and involution. Biochem Cell Biol, in press.