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Circuits attenuating seizures under well-fed and food-deprived conditions in C. elegans male sex muscles

The circuits that allow organisms to control behavioral timing need to be tightly
regulated to ensure execution of appropriate environmental responses. Disrupting such
regulation results in individuals unable to perform tasks necessary for survival and
propagation. Identifying the molecular components regulating behaviors will enable
compensation where behavioral impediments to survival exist. To identify circuits of
behavioral regulation, I studied male mating behavior in the nematode Caenorhabditis
elegans. Specifically, I focused on the step wherein the male inserts his copulatory
spicules into the hermaphrodite vulva, as vulva penetration is required for successful
sperm transfer. This step must be tightly regulated; if the spicules protract too soon or
not at all, vulva penetration and thus successful mating will not occur.
In this dissertation, I elucidate the circuits regulating sex-muscle excitability
under standard conditions and describe how these pathways are augmented to further
reduce excitability under food deprivation conditions. I employ a variety of assays to
identify and analyze these circuits, including genetic manipulation, biochemical
techniques, and behavioral assays. Under standard conditions the calcium/calmodulin-dependent protein kinase II (CaMKII) encoded by unc-43 is required to inhibit C.
elegans male sex-muscle seizures; under conditions where food is scarce, I propose that
CaMKII is further up-regulated to activate the EAG K+ channel EGL-2 through a direct
interaction. The CaMKII/EGL-2 interaction functions to attenuate calcium influx from
L-type voltage-sensitive calcium channels (L-VGCCs), while CaMKII also downregulates
calcium influx from ryanodine receptors. Additionally, another K+ channel,
the voltage- and calcium-sensitive big current channel SLO-1, attenuates sex-muscle
excitability by inhibiting L-VGCCs under food deprivation conditions. In conclusion,
CaMKII and EGL-2?s paralog, UNC-103/ERG-like K+ channel, are required when food
is plentiful to prevent premature sex-muscle contractions, while food deprivation reduces
cell excitability and thereby inhibits inappropriate seizures through CaMKII, EGL-2, and
SLO-1.

Identiferoai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-2009-05-618
Date2009 May 1900
CreatorsLeboeuf, Brigitte L.
ContributorsGarcia, Luis R.
Source SetsTexas A and M University
LanguageEnglish
Detected LanguageEnglish
TypeBook, Thesis, Electronic Dissertation, text
Formatapplication/pdf

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