Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, England, ++44-1223-333976,
Activity-dependent synaptic plasticity has generally been implicated in the refinement
and modification of neural circuits during development and in learning. In Drosophila, mutations
leading to an altered excitability of neurons also cause morphological alterations at the larval
motoneuron terminals. In hyperexcitable mutants like Shaker and ether-a-gogo the axon terminals
show excessive branching and an increase in the number of synaptic boutons. Similar effects have
also been found in dunce mutants indicating a role for the cAMP cascade in activity
dependent synaptic plasticity.
CaM kinase II is a mediator of activity dependent calcium ion increase. Transformants
carrying the gene for a specific inhibitor of this kinase are impaired in associative
learning and show an increase in the number of nerve terminal branches.
Synaptic transmission can be completely eliminated in neurons by expressing tetanus toxin light chain under UAS-control using the GAL4 system. In a screen we discovered a line in which GAL4 is expressed in several motoneurons which innervate the larval bodywall muscles. Expression can be found in the RP3 neuron, which innervates muscles 6 and 7 and in the motoneurons innervating muscles 12 and 13, respectively. This line has been used to target expression of tetanus toxin to these neurons. The expression of the toxin during larval development does not lead to any significant changes in the morphology of the axon terminals or the number of synaptic boutons.
We have used this system to test, whether the morphological alterations found in CaM kinase II inhibited nerve terminals are due to changes in synaptic activity. If tetanus toxin is expressed in CaM kinase II inhibited motoneurons during larval development, these neurons show a normal branching pattern and the number of synaptic boutons is wildtype. Other effects of CaM kinase II inhibition, like ectopic nerve entry points and ectopic branches cannot be rescued by elimination of synaptic transmission. This results suggest, that CaM kinase II plays a dual role: it is involved in activity dependent morphological plasticity, but also plays a role in activity independent neural development.
We are currently testing other signalling molecules, which are thought to be involved in learning and memory, such as PKA, Gas and Gai, for their role in activity dependent morphological plasticity.