Event:

Homeostatic modulation of neurotransmitter release

Given the complexity of the nervous system and its capacity for
change, it is remarkable that robust, reproducible neural function and
animal behavior can be achieved. It is now apparent that homeostatic
signaling systems have evolved to stabilize neural function. The
major focus of my research is the identification of the molecular
mechanisms underlying the stabilization of synaptic transmission
through the precise, homeostatic regulation of presynaptic
neurotransmitter release.

I am studying this question by employing a combination of forward
genetics and physiological analysis of synaptic transmission at the
neuromuscular synapse of the genetic model organism Drosophila. My
data suggest that homeostatic modulation of transmitter release
involves at least two genetically separable processes: The enhancement
of presynaptic calcium influx through CaV2.1 calcium channels (1), and
an increase in the number of release-ready vesicles that requires
the presynaptic protein RIM (2). In addition, I have provided genetic
evidence for a form of negative regulation that acts to oppose the
expression of synaptic homeostasis by defining a role for the
presynaptic proteins Rab3-GAP and Rab3 in the homeostatic control of
release (3).

In the future, I hope to continue to harness the power of Drosophila
genetics for new gene discovery, and translate this new information
into the vertebrate central nervous system, where analogous
homeostatic phenomena have been observed.

References:

1. Müller, M. & Davis, G. W. Transsynaptic control of
presynaptic Ca2+ influx achieves homeostatic potentiation of
neurotransmitter release. Curr. Biol. 22, 1102–1108 (2012).

2. Müller, M., Liu, K. S. Y., Sigrist, S. J. & Davis, G. W. RIM
controls homeostatic plasticity through modulation of the
readily-releasable vesicle pool. J. Neurosci. 32, 16574–16585 (2012).

3. Müller, M., Pym, E. C. G., Tong, A. & Davis, G. W. Rab3-GAP
Controls the Progression of Synaptic Homeostasis at a Late Stage
of Vesicle Release. Neuron 69, 749–762 (2011).