Synaptic and hormonal modulation of a neuronal oscillator: a search for molecular mechanisms.

1. The central ganglia of a number of gastropod molluscs (including the marine snail Aplysia californica and the terrestrial snail Helix pomatia) contain neurones which exhibit endogenous patterns of oscillatory activity. 2. This oscillatory activity can be modulated for long periods of time by synaptic and hormonal stimulation. 3. Stimulation of appropriate pre-synaptic nerves causes long-lasting hyperpolarization in these neurones, with complete abolition of oscillatory activity. This synaptic response is mediated by an increase in K+ conductance, together with a decrease in inward (Na+/Ca2+) conductance. The ionic conductances affected by synaptic stimulation are those responsible for producing the rhythmic oscillations. 4. The oscillatory activity can also be modulated by the vertebrate neurohyophyseal peptides, vasopressin and oxytocin, and by an endogenous peptide-containing extract of molluscan ganglia. In contrast to synaptic stimulation, these agents cause an increase in oscillatory activity. 5. The endogenous molluscan factor which produces an increase in oscillatory activity can be purified by affinity chromatography on bovine neurophysin linked to Sepharose. This indicates that the molluscan nervous system may contain a neurohypophyseal-like peptide. 6. Oscillatory activity can be modulated by manipulation of cyclic nucleotide metabolism in these neurones. Increases in cAMP alone are associated with abolition of oscillatory activity; this mimics long-lasting synaptic hyperpolarization. Increases in cAMP and cGMP together are associated with an increase in oscillatory activity and mimic the effects of the vertebrate and molluscan peptides. Thus, it is possible that cyclic nucleotides play a role in these physiological responses.