Kitchener Lab ~ Major Projects

Project 1 - The development of the viscero-sensory system.

The orbital and ventral prefrontal brain regions are of utmost importance in successful social interaction and thus in survival. Prefrontal regions receive sensory information, not only from exteroceptive sensory system but also from the internal organs, (the visceral, or enteroceptive sensory system).

The functions of prefrontal cortical regions are difficult to analyse, but a hitherto unexplored factor is the role of viscero-sensory input to the normal structural, neurochemical and functional development of these regions. In this project, selective neurotoxins will be used to drastically reduce the population of visceral afferents of neonatal rats; the viscero-sensory pathway through the brainstem and thalamus to the cortex of these rats will be analysed at different stages of subsequent development.

Anatomical analyses will determine the extent of any structural changes and also whether the normal pattern of neurochemical phenotype is present in the central pathways. Functional measures of cortical activation will be obtained using oxidative enzyme histochemistry and immunocytochemical detection of c-Fos induction (a marker of neuronal activation).

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Project 2 - Neuro-immune development: migration of cells through the brain.

This project examines the means by which cells navigate through the developing brain. Two type of cellular migration will be studied: 1) Neurons in the developing brain not only take up a position in the tissue of the developing brain, they must make connection, via their axons, with other neurons often at considerable distance away. Numerous previous studies have identified and characterised molecular entities that are present on or in the growing neurite process; in this project an in vitro organ culture system will be used to determine which cell-surface molecular structures of the growing neurite are required for axonal migration.

Because of its relative simplicity and well-understood connectivity, the organ culture system that will be used is the embryonic rat spinal cord with the invasion of sensory afferents from the dorsal root ganglia. 2) A different, although possibly related migratory phenomenon is seen during the development of the brain’s immune system.

The microglial cells are the main immune effector cell of the CNS and it is generally agreed that the CNS microglia derive from blood-borne myeloid lineage cells that invade the developing brain, transform into amoeboid phagocytes, and take-up residence in the brain as highly ramified microglial cell. As in the first part of this project, the in vitro organ culture system will be employed to examine the route of entry and the mechanisms by which adhesion and transmigration occur.