Previous intracellular recordings from Ascaris motorneurons and some interneurons revealed that these cells do not show the classical voltagesensitive action potentials characteristic of other nervous systems (Davis, R.E. and A.O.W. Stretton, J. Neurosci., 9:415, 1989; Angstadt, J.D. et al., J. Comp. Neurol., 284:374, 1989). The existence of discrete EPSPs and IPSPs in some classes of motorneurons, however, suggested that spikes are being generated in some presynaptic interneurons. Extracellular suction electrode recordings made over the nerve cords and over muscle cells have revealed fast spike activity of two general categories: (l) small amplitude, short duration, relatively simple biphasic spikes exclusively associated with the ventral nerve cord and (2) larger amplitude, longer duration spikes which are frequently multiphasic. The small spike population can show a variety of patterns of firing activity, has been correlated with motorneuron PSPs, and is not correlated with intracellularly recorded ventral muscle events. This population of signals probably originates in interneurons responsible for the motorneuron PSPs and, by means of those PSPs, may play a role in the generation of patterned motorneuronal, and ultimately behavioral, activity. The large spike population is relatively infrequent in occurrence, is correlated with intracellularly recorded muscle events and can be manipulated by polarizations of presynaptic motorneurons as would be expected if this population originates in muscle. Pharmacological experiments involving excitatory amino acids (EAA) and their analogs reveal significant depolarizing responses in DE2 (DB) motorneurons to application of glutamate and other EAA analogs. At best, only very weak responses are seen in DEl (AS) or DI (DD) to such applications. We are further characterizing these various spike events and the EAA pharmacology to determine their role in locomotory behavior. (USPHS Grant 15429)

Davis RE et al. (1993) International C. elegans Meeting "Excitatory amino acid (EAA) studies in the motornervous system of Ascaris: pharmacological evidence for a kainate-preferring receptor-conductance and an electrogenic glutamate pump."

Davis RE, Stretton AOW

[

International C. elegans Meeting,

1993]

Kazumi Sakata et al. (2002) Japanese Worm Meeting "A Computer Simulation of the Nervous System of C. elegans"

Tokumitsu Wakabayashi, Ryuzo Shingai, Taro Ogurusu, Kazumi Sakata, Katsunori Hoshi

[

Japanese Worm Meeting,

2002]

Computer simulation of the neural system of Caenorhabditis elegans was performed. The model neuron had Hodgkin-Huxley type voltage sensitive channels. Parameters of the channels were obtained by curve fitting to the electrophysiological experimental data (Pierce-Shimomura JT, et al. Nature. 410 , 694 (2001)). Chemical synapses were located within neurites and their transmission properties were set to be graded as those of Ascaris suum (Davis RE, Stretton AO. J Neurosci. 9 , 415 (1989)). Gap junction was reconstructed as the connection of neurite membranes between pre- and post-synaptic neurons. The following conditions were necessary to reconstruct realistic changes of membrane potentials; (1) the conductance of gap junction was lower than that of the mammal, (2) the time constants of the channels at chemical synapse was about 3 msec. When the synaptic delay, which included the whole time course from activation of presynaptic soma membrane to that of postsynaptic cell, was set to 500 msec, the whole network system showed periodic perturbation of membrane potential. However, this synaptic delay is very long and not realistic. Therefore, there should be some factors which make the practical delay long as 500 msec. Additionally, we discuss possibility of other factors to generate periodic activation of membrane potential, e.g., pacemaker-like neuron as observed in Ascaris (Angstadt JD, Stretton AOW. J Comp Physiol A. 166 , 165 (1989)).

Starr, D. et al. (2015) International Worm Meeting "UC Davis-University of Maryland Eastern Shore Graduate Admissions Pathway: Collaborating to broaden participation in molecular and cellular biology."

Starr, D., Hom, C.

[

International Worm Meeting,

2015]

STEM professionals in the 21st century remain predominantly Caucasian/white, in spite of decades of work by professional societies, colleges and universities, and individual scientists to broaden participation. This multifaceted problem includes concerns among students and faculty at minority-serving institutions about the economics of career choice, family pressure to pursue a career in a biomedical field, and limited exposure to natural history. Further, institutional efforts in recruitment by research universities remain rooted in graduate fairs that target senior undergraduates from groups underrepresented in science, whereas connections made via shared research networks provide a more sure means to admission in molecular and cell biology. The UC Davis-University of Maryland Eastern Shore (UMES) Molecular and Cellular Biology Graduate Admissions Pathways (MCBGAP) program addresses this challenge via collaborations between faculty at the two institutions and a research co-mentoring program that brings UMES undergraduates to UC Davis for summer research. The program is funded by a grant from the University of California Office of the President and the UC Davis College of Biological Sciences.MCBGAP supported two cohorts of five UMES students in the summers of 2014 and 2015. The MCBGAP program consists of reciprocal student-faculty visits, close interactions between key UC Davis and UMES faculty, monthly Skype meetings that involve mentors and students, and research, professional development, and field trips in the summer. MCBGAP has catalyzed change both at UMES, where students are given the opportunity to self-identify as researchers at a tier 1 research university, and at UC Davis, where increased numbers of faculty recognize the need to be proactive in graduate recruiting and admissions, and multiple deans have committed time to mentor students and funds to support additional undergraduates from Historically Black Colleges and Universities for summer research and mentoring. The experience has also inspired us to apply for a Postbaccalaureate Research Education Program (PREP) from the NIH.

Park, Eun Chan et al. (2013) International Worm Meeting "Mitochondrial Dynamics And Behavioral Plasticity In Response To Oxygen Deprivation Are Linked Through HIF-1."

Salazar-Vasquez, Nathaly, Ghose, Piya, Park, Eun Chan, Tabakin, Alexandra, Rongo, Christopher

[

International Worm Meeting,

2013]

C. elegans can survive extreme oxygen deprivation (anoxia, < 0.1% O2) by entering into a suspended animation state during which locomotory behavior and development arrest. Upon re-exposure to normoxic conditions (21 % O2), animals resume their behavior and normal development. The underlying mechanism of this stress response is not well understood. Here we show that neuronal mitochondria undergo fission in response to anoxia co-temporaneously with the onset of suspended animation, followed by re-fusion upon re-oxygenation, suggesting that mitochondrial dynamics might contribute to anoxia-induced suspended animation. We find that the hypoxia response pathway, including EGL-9 and HIF-1, regulates the reconstitution of mitochondria following re-oxygenation. Under conditions of normal oxygen, EGL-9 represses the activity of HIF-1, a transcription factor that promotes the expression of hypoxia-response genes. Loss of function mutations in egl-9 result in rapid re-fusion of mitochondria and behavioral recovery from suspended animation following re-oxygenation; both phenotypes require HIF-1 activity. In addition, the mitochondria are significantly larger in egl-9 mutants after re-oxygenation than they were prior to anoxia exposure - a phenotype that resembles the stress-induced mitochondria hyperfusion (SIMH) that has been observed in mammalian cells. Both the changes in mitochondrial dynamics and suspended animation recovery of egl-9 mutants can be rescued by expressing wild-type EGL-9 solely in neurons. Mitochondrial hyperfusion and rapid recovery observed in egl-9 mutants following anoxia are modulated by STL-1, a mammalian stomatin-like protein (SLP2) homologue that is reported to function in SIMH. Our results suggest the existence of a conserved stress response involving changes in mitochondrial fission and fusion, and demonstrate that the behaviors executed by a simple neural circuit can be regulated through changes in mitochondrial dynamics.

Korzelius, Jerome Peter et al. (2009) International Worm Meeting "Cell cycle re-entry in terminally differentiated body wall muscle cells."

The, Inge, Groot Koerkamp, Marian, Van den Heuvel, Sander, Holstege, Frank, Korzelius, Jerome Peter, Portegijs, Vincent

[

International Worm Meeting,

2009]

It is poorly understood why cells lose the ability to enter the cell cycle upon terminal differentiation. Insight into this process would be of critical importance for regenerative medicine and cancer biology. We use the C. elegans body wall muscle (bm) as a model system to study cell cycle re-entry in the context of animal development. Previous work has demonstrated that knockdown of the negative G1/S regulators lin-35 Rb and cki-1 Kip1 causes overproliferation in certain blast cell lineages but it does not affect proliferation of differentiated cells like the body wall muscle. We set out to test whether re-activation of G1 Cyclin/Cdk complexes in differentiated bm cells can trigger cell cycle re-entry. We expressed combinations of the positive G1/S regulators CYD-1/CDK-4 and CYE-1/CDK-2 in the body wall muscle. Interestingly, a combination of CYE-1 together with mutant CDK-2AF (lacking the negative regulatory phosporylation sites) stimulated cell cycle re-entry in the bm lineage. Specifically, first stage larva showed the normal number of body wall muscle nuclei, while subsequent larval stages showed expression of a degradable S-phase marker, mitosis-specific histone H3 phosphorylation, condensed chromosomes and extra nuclear division. However, these bm cells did not incorporate EdU, a thymidine orthologue, suggesting that these cells have an altered cell cycle program without S-phase. To gain insight into the transcriptional changes that take place in a body wall muscle cell re-entering the cell cycle, we performed tissue-specific microarray analysis (Roy et al., 2002). Genes required for S-phase, mitosis and DNA damage response were highly enriched among the upregulated genes in dividing bm cells. These results suggest that although the transcriptional program for DNA-replication is activated, the cell still cannot undergo S-phase. In contrast, we did not observe any changes in genes known to be required for body wall function and we witnessed no changes in muscle structure or function in these animals. In summary, this work demonstrates that terminally differentiated bm cells can activate cell cycle gene transcription and go through mitosis upon G1/S Cyclin/Cdk overexpression. However, the absence of DNA synthesis upon re-entry suggests that there are additional controls that act to prevent re-entry in differentiated bm cells. These findings open up avenues for forward and reverse screens to identify additional genes that act in cell cycle re-entry.

Stanley I Shyn et al. (2001) International C. elegans Meeting "A genomic approach to understanding the actions of fluoxetine"

Rajesh Ranganathan, Stuart K Kim, Eric Miska, William R Schafer, Kyle Duke, Bob Horvitz, Stanley I Shyn

[

International C. elegans Meeting,

2001]

Re-uptake blockers are a class of antidepressants proposed to achieve their clinical effects in people by inhibiting presynaptic norepinephrine and/or serotonin re-uptake transporters, which normally function to terminate transmitter signaling at synapses. It has never adequately been explained, however, why therapeutic relief of depression takes weeks when this particular action of re-uptake blockers occurs within hours of drug administration. 1 A requirement for some form of adaptation at synapses is a frequently cited possibility, but recent work has also highlighted that there are a myriad of non-classical targets for re-uptake blockers, such as EAG-like K + -channels (blocked by imipramine) 2 and novel membrane-spanning proteins typified by NRF-6 and NDG-4, identified as fluoxetine targets in a recent screen in worms 3 . With the recent discovery of mutants in mod-5 , a gene encoding the C. elegans serotonin re-uptake transporter, 4 a new approach to tackling this long-standing question has emerged. Utilizing the DNA microarray facility at Stuart Kim's laboratory in Stanford, we have begun work on a gene chip project to perform a four-way comparison between N2 and mod-5(n3314) worms ( n3314 is a 1.6 kb deletion in the mod-5 genomic locus), each on and off fluoxetine. We hope to understand what baseline transcriptional differences exist between the two genotypes, how similar the effects of chronic fluoxetine in N2 are to the effects of a complete absence of MOD-5 in mod-5(n3314) worms, and to identify which gene expression changes induced by fluoxetine are MOD-5-dependent and which are MOD-5-independent. A preliminary experiment is expected to be completed by the end of April, 2001. 1 Schafer WR, Cell 98 :551-554 2 Weinshenker D et al . J Neurosci 19 :9831-9840 3 Choy RK et al . Mol Cell 4 :143-152 4 Ranganathan R and Horvitz HR, 1999 International Worm Meeting, abstract 70

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