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Molecular Mechanisms Regulating Cell Intrinsic and Synaptic Homeostasis: Compensation in Drosophila shal Mutants

  • Author(s): Bergquist, Sharon Brie
  • Advisor(s): Davis, Graeme W
  • Jan, Lily Y
  • et al.
Abstract

Homeostasis is the property of a system to precisely maintain constant function at a set point level of activity. Within the nervous system homeostatic mechanisms are thought to constrain neural plasticity to maintain stable activity over an animal's lifetime. Homeostatic modulation of both synaptic efficacy and intrinsic neuronal excitability has been demonstrated in vertebrates and invertebrates (Davis & Goodman 1998a, Turrigiano & Nelson 2000, Marder & Prinz 2002, Perez-Otano & Ehlers 2005). Work in the laboratory of Graeme Davis has shown at the Drosophila neuromuscular junction (NMJ) that decreases in muscle sensitivity to neurotransmitter, through either genetic mutation of the Glutamate Receptor subunit IIA or pharmacological block of this same subunit, result in enhanced presynaptic neurotransmitter release. This increase in neurotransmitter release, or quantal content, precisely compensates for the block in postsynaptic sensitivity, restoring muscle excitation back to baseline. This process has been termed synaptic homeostasis. Work in many labs has demonstrated that the loss or mutation of a single ion channel results in the compensatory changes in abundance or function of other ion channels that often restore neuronal activity. These compensatory changes in ion channels are thought to be cell-intrinsic homeostasis.

There are many open questions regarding homeostatic compensation within the nervous system and the underlying molecular mechanisms. My thesis work focuses on the mechanisms underlying the involvement of voltage-gated potassium channels, Shal and Shaker (Sh), in both synaptic and cell-intrinsic homeostasis and concludes with a broader description of the modulation of ion channel expression in response to the loss of several independent ion channels in Drosophila motoneurons.

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