The Journal of Neuroscience, March 1, 1999, 19(5):1620-1635
Plasticity of First-Order Sensory Synapses: Interactions between
Homosynaptic Long-Term Potentiation and Heterosynaptically Evoked
Dopaminergic Potentiation
Sanjay S.
Kumar2 and
Donald S.
Faber1
1 Department of Neurobiology and Anatomy, Medical
College of Pennsylvania-Hahnemann University, Philadelphia,
Pennsylvania 19129, and 2 Neuroscience Graduate Group, The
David Mahoney Institute of Neurological Sciences, University of
Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
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-hydroxytyramine). These modifications are attributable to the activation of distinct
intracellular kinase cascades. Although dopamine-evoked potentiation
(DEP) is mediated by the cAMP-dependent protein kinase (PKA),
tetanization most likely activates a Ca2+-dependent
protein kinase via an increased intracellular Ca2+
concentration. We present evidence that the eighth nerve tetanus that
induces LTP does not act by triggering dopamine release, because it is
evoked in the presence of a broad spectrum of dopamine antagonists. To
test for interactions between these pathways, we applied the
potentiating paradigms sequentially. When dopamine was applied first,
tetanization produced additional potentiation of the mixed synaptic
response, but when the sequence was reversed, DEP was occluded,
indicating that the synapses potentiated by the two procedures
belong to the same or overlapping populations. Experiments were
conducted to determine interactions between the underlying
regulatory mechanisms and the level of their convergence. Inhibiting PKA does not impede tetanus-induced LTP, and chelating postsynaptic Ca2+ with BAPTA does not block DEP,
indicating that the initial steps of the induction processes are
independent. Pharmacological and voltage-clamp analyses indicate that
the two pathways converge on functional AMPA/kainate receptors for
the chemically mediated EPSP and gap junctions for the electrotonic
component or at intermediaries common to both pathways. A cellular
model incorporating these interactions is proposed on the basis of
differential modulation of synaptic responses via receptor-protein phosphorylation.
Key words:
synaptic plasticity; long-term potentiation; dopamine-evoked potentiation; intracellular mechanisms; Mauthner cell; phosphorylation; glutamate receptors
Copyright © 1999 Society for Neuroscience 0270-6474/99/1951620-16$05.00/0
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