AXONS, BUT NOT CELL-BODIES, ARE ACTIVATED BY ELECTRICAL-STIMULATION IN CORTICAL GRAY-MATTER II - EVIDENCE FROM SELECTIVE INACTIVATION OF CELL-BODIES AND AXON INITIAL SEGMENTS

The results presented in the companion paper showed that extracellular electrical stimulation of the gray matter directly activates axons, b ut not cell bodies. The second set of experiments presented here was d esigned to separate the contribution of the axon initial segments and cell bodies from that of the axonal branches to the pool of presynapti c neuronal elements activated by electrical stimulation. For that purp ose, N-methyl-D-aspartate (NMDA) iontophoresis was used to induce a se lective inactivation of the cell body and of the adjoining portion of the axon by depolarization block, without affecting axonal branches th at lack NMDA receptors. After NMDA iontophoresis, the neurons located near the iontophoresis electrode became unable to generate action pote ntials in an irreversible manner. When the NMDA-induced depolarization block was performed at the site of electrical stimulation, an unexpec ted increase in the amplitude of the orthodromic responses was observe d. Several control experiments suggested that the field potential incr ease was due to changes of the local environment in the vicinity,of th e iontophoresis pipette, which led to an increased excitability of the axons. After the period of superexcitability, the orthodromic respons es displayed an amplitude that was 15-20% lower than that observed bef ore the NMDA-induced depolarization block, even though cell bodies and axon initial segment at the site of stimulation could not be activate d by electrical stimulation. This result shows a low contribution for axon initial segments to the pool of neuronal elements activated by th e electrical stimulation. Altogether, these experiments demonstrate th at the postsynaptic responses obtained after electrical stimulation of the cortical gray matter result almost exclusively from the activatio n of axonal branches. Since the neocortex is organised as a network of local and long-range reciprocal connections, great attention must be paid to the interpretation of data obtained with electrical stimualtio n.