Plasticity of first-order sensory synapses: Interactions between homosynaptic long-term potentiation and heterosynaptically evoked dopaminergic potentiation

Persistent potentiations of the chemical and electrotonic components of the eighth nerve (NVIII) EPSP recorded in vivo in the goldfish reticulospinal neuron, the Mauthner cell, can be evoked by afferent tetanization or local dendritic application of an endogenous transmitter, dopamine (3-hydroxytyra mine). These modifications am attributable to the activation of distinct in tracellular kinase cascades. Although dopamine-evoked potentiation (DEP) is mediated by the cAMP-dependent protein kinase (PKA), tetanization most lik ely activates a Ca2+- dependent protein kinase via an increased intracellul ar Ca2+ concentration, We present evidence that the eighth nerve tetanus th at induces LTP does not act by triggering dopamine release, because it is e voked in the presence of a broad spectrum of dopamine antagonists. To test for interactions between these pathways, we applied the potentiating paradi gms sequentially. When dopamine was applied first, tetanization produced ad ditional potentiation of the mixed synaptic response, but when the sequence was reversed, DEP was occluded, indicating that the synapses potentiated b y the two procedures belong to the same or overlapping populations. Experim ents were conducted to determine interactions between the underlying regula tory mechanisms and the level of their convergence. Inhibiting PKA does not impede tetanus-induced LTP, and chelating postsynaptic Ca2+ with BAPTA doe s not block DEP, indicating that the initial steps of the induction process es are independent. Pharmacological and voltage-clamp analyses indicate tha t the two pathways converge on functional AMPA/kainate receptors for the ch emically mediated EPSP and gap junctions for the electrotonic component or at intermediaries common to both pathways. A cellular model incorporating t hese interactions is proposed on the basis of differential modulation of sy naptic responses via receptor-protein phosphorylation.