The second study revealing new oligodendrocyte functions explores the consequences of action potentials in axons communicating with mature oligodendrocytes and the reciprocal effects on impulse propagation. Yamazaki and colleagues (2007)
recorded electrophysiological responses from mature oligodendrocytes in the myelinated region of rat hippocampus, the alveus (). This enables measurement of action potential conduction velocity in axons of the pyramidal neurons. Exogenously applied glutamate elicited depolarizing responses through NMDA and non-NMDA receptors, and electrical stimulation at the border between the alveus and striatum orens evoked inward currents in the oligodendrocyte that were mediated by glutamate and potassium channels. Theta-burst stimulation of the hippocampus, which resembles in vivo activity and induces long-term potentiation of hippocampal synapses, depolarized the oligodendrocytes to a potential of -48 mV from a resting membrane potential of -75 mV. Because axons are known to release glutamate and potassium after firing bursts of action potentials (Kriegler and Chiu 1993
; Kukley and others 2007
; Ziskin and others 2007
), the depolarizing response in oligodendrocytes to the axonal firing is not unexpected; indeed, they were observed in optic nerve glia (astrocytes) 40 years ago (Orkand and others 1966
), but the significance, if any, of the depolarization in oligodendrocytes is obscure.
Fig. 2 Schematic diagram of experiments by Yamazaki and others (2007) revealing that depolarization of oligodendrocytes can decrease the latency of action potentials in axons in the rat hippocampus. Theta burst stimulation of axons depolarized the oligodendrocytes (more ...)
To explore the hypothesis that this activity-dependent axon-glial communication might have consequences for neuronal function, the investigators performed paired whole-cell recordings between oligodendrocytes in the alveus and pyramidal cells in CA1 while stimulating axons from the pyramidal cells distally in the alveus to elicite antidromic action potentials (). In a subset of these paired-cell recordings (4 of 27), the latency of the antidromically activated spikes decreased when the oligodendrocyte was depolarized to -30 to -20 mV (). After the experiment, the oligodendrocytes and pyramidal cells filled with biocytin during the paired recording were examined histologically (). In those experiments where the action potential latency had decreased after depolarizing the oligodendrocyte, the filled axon was observed to pass through a myelinated segment extending from the depolarized oligodendrocyte. In those cases where there was no decrease in action potential latency, the axons did not pass through the oligodendrocyte that had been depolarized. The authors speculate that the increase in conduction velocity may be caused by osmotic swelling of the myelin sheath secondary to transmembrane ion fluxes during depolarization.
Fig. 3 Depolarization of oligodendrocytes in the rat hippocampus can reduce action potential latency through the axons ensheathed by the cell. A, Axon (triangles) and oligodendrocyte filled with biocytin in paired whole-cell recordings. B, Depolarization of (more ...)
These observations are based on a small number of cases, but they are unprecedented. If confirmed by further experiments and the mechanisms can be elucidated, the implications of modulating impulse propagation speed by rapid activity-dependent responses in myelin will not only change our current concept of myelin but also add a new dimension to information processing in the brain. Communication between neurons is primarily regulated by changes in synaptic efficacy, but in theory, information processing would also be regulated by changes in conduction velocity, which would affect spike arrival timing and synchrony (Fields 2005
). Spike arrival timing can be critical in information coding (Gollisch and Markus 2008
). Because an individual oligodendrocyte can myelinate 20 or more axons simultaneously, all the axons under the domain of the same glial cell would be influenced in a coordinated manner. The consequences of glial involvement in information processing, particularly in white matter, are yet to be explored experimentally and conceptually.