Ionic and synaptic mechanisms underlying a brainstem oscillator: an in vitro study of the pacemaker nucleus of Apteronotus.

1. In an in vitro preparation of the medullary pacemaker nucleus of Apteronotus, the consequences of a variety of ionic and pharmacological manipulations upon both ongoing activity and synaptic modulation of the nucleus were assessed. 2. Spontaneous rhythmicity in the pacemaker nucleus was found to be Na+-, K+-, and Ca(2+)-dependent. The extreme sensitivity to 4-aminopyridine (4-AP) relative to other treatments suggested that the K+ A-current is a critical element in the oscillations. 3. Elevated K+ or 4-AP were titrated to concentrations that suppressed spontaneous oscillations, but allowed modulatory, 'chirp' epsps to persist. The transition to elevated K+ revealed oscillatory properties in some neurons in the form of epsp-induced ringing 4. Threshold concentrations of 4-AP sufficient to halt oscillations, caused epsps to become larger and complex, increased input resistance, and enhanced the effects of current injection on epsp amplitude. A greater degree of voltage-sensitivity was also seen in later components of the complex epsp. 5. Several treatments presumed to increase Ca2+ caused desynchronization of firing and revealed diverging intrinsic frequencies among cells.