Craig Jahr

Neurons in the brain transmit information to each other through specialized connections called synapses. Craig Jahr and his coworkers use electrophysiological techniques to focus on synaptic transmission involving the release of glutamate, a chemical neurotransmitter that can cause synaptically connected neurons to become excited. The excitation is generated by the binding oflutamate to specific receptors embedded in the neuronal membrane. These receptors span the neuronal membrane and, when bound by glutamate, alter their three-dimensional structure to open a water-filled pore that connects the environment outside the cell with the intracellular cytoplasm. Ions such as sodium and calcium can flow through these pores, or ion channels, and decrease the electrical potential across the cell membrane, as well as raise the intracellular calcium ion concentration. The level of cytoplasmic calcium is important because itcontrols the activity of many intracellular enzymatic pathways and is linked to alterations in the strength of synaptic excitation.

Jahr and his colleagues have found that glutamate released from the presynaptic terminal is cleared from the cleft very rapidly, within two to three milliseconds. The mechanism that removes glutamate from the synaptic cleft has not been determined. Although membrane-spanning proteins that transport extracellular glutamate back into cells are present, it is not certain that they function on the millisecond time scale. These transporters may clear extrasynaptic areas of glutamate so that synaptically released transmitter can diffuse rapidly and become diluted in the extracellular space. Jahr and coworkers have recently shown that glutamate transporter blockers can prolong the postsynaptic effects of glutamate release, suggesting that glutamate uptake is important for normal synaptic function.

It has been known for years that neurons and glial cells of the CNS are in a symbiotic relationship, the activity of one closely followed by the other. The very rapid signaling between cells mediated by direct synaptic connections, however, was thought to be restricted to neurons. This rule appears to be breached by a class of glial cells called oligodendrocyte precursor cells (OPCs) which are found throughout the CNS. During development, some OPCs differentiate into mature, myelinating oligodendrocytes, but some remain in this suspended developmental stage of precursor cell through adulthood. The Jahr lab has found that OPCs in the hippocampus receive direct, glutamatergic, excitatory synaptic inputs from the Schaffer collateral afferents. Others previously reported that glutamate can prevent OPCs from differentiating into mature oligodendrocytes, but the source of the glutamate was not known. These synaptic connections provide a source of glutamate and may, therefore, prevent further development of OPCs in normal conditions. If pathological insults disrupt the synaptic drive to the OPCs, these cells could begin to mature and become myelinating oligodendrocytes, possibly repairing areas of demyelination. In addition, synaptically activated OPCs may be a source of trophic substances or transmitters that could alter the physiology of neighboring neurons.

Bergles, DE, Roberts, JDB, Somogyi, P and Jahr, CE (2000) Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus. Nature 405:187-191.

Diamond, JS and Jahr, CE (2000) Synaptically released glutamate does not overwhelm transporters on hippocampal astrocytes during high-frequency stimulation. J. Neurophysiol. 83:2835-2843.

Wadiche, JI and Jahr, CE (2001) Multivesicular release at climbing fiber-Purkinje cell synapses. Neuron (in press).

To contact Dr. Jahr directly: jahr@ohsu.edu