The Journal of Neuroscience, March 15, 2000, 20(6):2104-2111
cAMP-Dependent Plasticity at Excitatory Cholinergic Synapses in
Drosophila Neurons: Alterations in the Memory Mutant
Dunce
Daewoo
Lee and
Diane K.
O'Dowd
Departments of Developmental and Cell Biology, Anatomy and
Neurobiology, University of California at Irvine, Irvine, California
92697-1280
It is well known that cAMP signaling plays a role in regulating
functional plasticity at central glutamatergic synapses. However, in
the Drosophila CNS, where acetylcholine is thought to be
a primary excitatory neurotransmitter, cellular changes in neuronal communication mediated by cAMP remain unexplored. In this study we
examined the effects of elevated cAMP levels on fast excitatory cholinergic synaptic transmission in cultured embryonic
Drosophila neurons. We report that chronic elevation in
neuronal cAMP (in dunce neurons or wild-type neurons
grown in db-cAMP) results in an increase in the frequency of
cholinergic miniature EPSCs (mEPSCs). The absence of alterations
in mEPSC amplitude or kinetics suggests that the locus of action is
presynaptic. Furthermore, a brief exposure to db-cAMP induces two
distinct changes in transmission at established cholinergic synapses in
wild-type neurons: a short-term increase in the frequency of
spontaneous action potential-dependent synaptic currents and a
long-lasting, protein synthesis-dependent increase in the mEPSC
frequency. A more persistent increase in cholinergic mEPSC frequency
induced by repetitive, spaced db-cAMP exposure in wild-type neurons is
absent in neurons from the memory mutant dunce. These
data demonstrate that interneuronal excitatory cholinergic synapses in
Drosophila, like central excitatory glutamatergic synapses in other species, are sites of cAMP-dependent plasticity. In
addition, the alterations in dunce neurons suggest that
cAMP-dependent plasticity at cholinergic synapses could mediate changes
in neuronal communication that contribute to memory formation.
Key words:
Drosophila; nAChRs; cAMP-dependent plasticity; mEPSC; dunce; cholinergic synaptic transmission
Copyright © 2000 Society for Neuroscience 0270-6474/00/2062104-08$05.00/0