Neurons are the cells of the brain that are the units for information processing. Understanding the properties of their cell membranes, including excitability and neurotransmission between neurons, is crucial to an understanding of brain function. In complex mammalian brains it has been technically difficult to study membrane properties of identifiable cells, particularly in the cerebral cortex. Conversely, the isolation of single cells in a dish ("in vitro") for membrane recordings makes it difficult to identify the type of neurons these cells were in the normal brain. This project will provide a new approach to try to establish reliable methods to culture and identify cell types or classes isolated from the cortex, and characterize the physiological and pharmacological responses of those neurons. Cells that project across the brain hemispheres, called callosal neurons, can be distinctly labelled by their uptake of non-toxic microscopic fluorescent beads. These cells will then be studied in vitro, either as cultured dissociated cells after removal from newborn rats, or in a thin-slice preparation taken from whole brain. Microelectrodes will be used to test the response of these cells to electrical stimuli across their membranes, to examine the nature of the currents of charged ionic particles that drive the excitable properties of the cells. These studies will compare changes in the cell properties with time since isolation or with time since birth, and will look for possible functional differ- ences among cells that appear morphologically similar. This approach to classify cortical cell types on the basis of membrane properties is technically very demanding, but success will be a breakthrough offering a powerful new way for electrophysiologists to study cortical processing.
