The negative (N)-wave evoked at various depths in the cuneate nucleus by stimulation of afferents in the ipsilateral forepaw or dorsal column has been studied in the rat. 2. Micro-iontophoretic applications of gamma-aminobutyric acid (GABA) into the vicinity of the recording electrode markedly reduced the amplitude of the negative wave, but only when recordings were made near the base of the cuneate nucleus. Nearer the surface of the medulla, GABA was much less effective. 3. A similar depth distribution obtained for the depression of the negative wave by micro-iontophoretic Mg2+ and enhancement by Ca2+. 4. Depression of the negative wave by conditioning stimulation of the afferent pathway also showed a similar depth distribution. The conditioned depression of the negative wave was most marked during the first 30 ms after the conditioning stimulus and this early depression could be antagonized by iontophoretic (+)-bicuculline methochloride. A lesser degree of conditioned inhibition of the negative wave persisted up to 80-200 ms but this was resistant to (+)-bicuculline methochloride. Thus, conditioned depression of the negative wave appeared to be mediated only in part by a GABA-like transmitter. 5. It is concluded that the negative wave recorded near the base of the cuneate nucleus has some of the predicted properties of a post-synaptic potential. These properties are not seen when the negative wave is recorded more superficially, near the surface of the medulla.
