Davis RE et al. (1982) Worm Breeder's Gazette "Membrane Properties of Ascaris Commissures"

Davis RE, Stretton AOW

[Worm Breeder's Gazette, 1982]

Microscopic studies (Stretton et al., PNAS, 75:3493, 1978; White et al., Phil. Trans., 275:327, 1916) have revealed the morphological similarities between motorneuronal types found in Ascaris des and those found in C. elegans. Based on the assumption that the function of morphologically analogous elements will be similar, we have previously predicted that types DAS, DB and DA (Ascaris types DE1, DE2 and DE3) are excitatory motorneurons whereas types VD and DD (Ascaris VI and DI) are inhibitory motorneurons. At the last C. elegans meeting (1981), we described techniques which allowed us to make the first intracellular recordings from Ascaris neurons. These recordings were made from the commissures of identified motorneurons. (Commissures are single motorneuron processes which connect the ventral and dorsal nerve cords. They occur in both Ascaris and C. elegans.) At that time, we noted that spontaneously occurring excitatory and inhibitory potentials were conducted with very little decrement for long distances along the commissure (~.5 cm). Using two intracellular microelectrodes for stimulation and recording, we have now determined the electrical ( cable) properties of commissures: [See Figure 1] Commissural membranes are similar to excitable membranes found in most other organisms in two of their properties: internal (axoplasmic) resistivity (Ri) and membrane capacitance (Cm). Commissures differ rather markedly from most other excitable membranes in their space constant (lambda) and membrane resistance (Rm). We suspect that the unusually high Rm is an inherent property of the commissural membrane itself since the Cm is similar to that of a single biological membrane. (Myelinated fibers with their wrapping of multiple membranes have a much lower Cm.) We are now examining this anatomically. The high Rm produces a long lambda which accounts for the ability of the commissural membrane to conduct spontaneous passive signals over long distances with only slight decrement. We have also examined electrical signals evoked by stimulation of the ventral nerve cord. To date, all of the signals we have observed are graded, i.e., the signals lack a clear threshold and their amplitude is a continuous function of stimulus strength. We have never observed spontaneous all- or-none action potentials nor have we been able to evoke them (at normal resting potential or after hyperpolarization). Thus, lacking this classical long-distance signalling mechanism, Ascaris motorneurons appear to rely on their unusual membrane properties. to convey information over the long distances separating the two nerve cords. Nonetheless, active voltage-dependent membrane channels do appear to be present as indicated by our ability to elicit anode-break responses. These responses, however, are themselves graded (i.e., they increase in amplitude with increasing strength of the hyperpolarizing pulse). The signalling, properties of the interneurons are as yet unknown, though we are in the process of investigating them. At this point, it is not possible to rule out the presence of an action potential mechanism in other nematodes ( including C. elegans). Such an active mechanism may, however, not be necessary; in fact, one might expect passive signalling to be the modus operandi in a system where only short distance signalling (on the order of one or a few millimeters) is required. If the Rm of neuronal membranes in C. elegans is the same as that in Ascaris commissures, a lambda of 0.9mm for a 0.5 m fiber (in adult C.e.) or 0. 4mm for a 0.1 m fiber (in the L1) would be expected. Thus passive signalling over the length of the animal is entirely feasible. We have also examined neuromuscular synaptic transmission. For both excitatory and inhibitory motorneurons, synaptic transmission is graded. In addition, we have evidence that Ascaris motorneurons tonically release neurotransmitter. It is easy to see how graded synaptic transmission can be an effective way to generate the continuous gradation of muscle contraction which underlies a locomotory wave (in contrast to integration of multiple non-graded neuronal elements which together could produce the same effect). It is also tempting to speculate that graded synaptic transmission and/or tonic neurotransmitter release may be important in the production and variation of muscle tonus comprising the hydrostatic skeleton.

Davis RE (1996) Parasitol Today "Spliced leader RNA trans-splicing in metazoa."

Davis RE

[Parasitol Today, 1996]

Spliced leader trans-splicing is a form of RNA processing originally described and studied in parasitic kinetoplastida. This mechanism of gene expression also occurs in parasitic and free-living metazoa. In this review, Dick Davis describes current knowledge of the distribution, substrates, specificity and functional significance of trans-splicing in metazoa.

Davis RE et al. (1981) International C. elegans Meeting "intracellular recordings from identified motorneurons in the nematode Ascaris."

Davis RE, Stretton AOW

[International C. elegans Meeting, 1981]

Davis RE et al. (1983) International C. elegans Meeting "motorneuron membrane constants and signaling properties in the nematode Ascaris."

Davis RE, Stretton AOW

[International C. elegans Meeting, 1983]

Davis RE et al. (1989) International C. elegans Meeting "electrphysiological studies of KNEFIRFamide, a peptide from the nematode A suum."

Stretton AOW, Davis RE

[International C. elegans Meeting, 1989]

Davis RE et al. (1992) Journal of Comparative Physiology A "Extracellular recordings from the motor nervous system of the nematode, Ascaris suum."

Davis RE, Stretton AOW

[Journal of Comparative Physiology A, 1992]

1. The close association of muscle and neurons in Ascaris suum makes it difficult to determine whether spikes recorded from nerve cords originate in muscle or neurons. We have developed criteria that distinguish muscle and neuronal activity. There are two categories of extracellular spikes. 2. The first category consists of spikes with a wide range of amplitudes, marked by large spikes. These spikes, which can be recorded over lateral muscle and over the dorsal and ventral nerve cords, are abolished when muscle is disrupted or removed, or when curare is applied. Large spikes are relatively infrequent, are correlated with intracellularly recorded events, and respond to polarization of motor neurons, implying that they originate in muscle. 3. The second spike category, small amplitude spikes, is exclusive to the ventral nerve cord, occurs more frequently than large spikes and displays patterned firing. Small spikes are not affected by muscle removal or by curare, and are correlated with motor neuronal postsynaptic potentials, but not with intracellularly recorded muscle events. We infer that they originate in neurons. 4. Low level activity recorded extracellularly over nerve cords may represent muscle activity due to tonic motor neuronal synaptic transmission. It responds to motro neuronal polarization and is

Davis RE et al. (1991) International C. elegans Meeting "EXTRACELLULAR RECORDINGS AND EXCITATORY AMINO ACID STUDIES IN THE MOTORNERVOUS SYSTEM OF ASCARIS."

Stretton AOW, Davis RE

[International C. elegans Meeting, 1991]

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. (1999) Proc Natl Acad Sci U S A "Transient expression of DNA and RNA in parasitic helminths by using particle bombardment."

LoVerde PT, Glorioso G, Davis RE, Ribeiro E, Parra A, Hodgson S

[Proc Natl Acad Sci U S A, 1999]

Parasitic helminths (worms belonging to several metazoan phyla) cause considerable morbidity and mortality in humans. They are an important veterinary problem, and they result in significant economic losses in animal grazing and agriculture. Experimental studies on parasitic helminths have been limited by a lack of parasite cell lines and methods for molecular genetic analyses. We evaluated particle bombardment (biolistics) as a strategy to introduce and express nucleic acids in these multicellular parasites. By using embryos of the parasitic nematode Ascaris as a model, we developed methods to introduce and express both DNA and RNA during several stages of Ascaris embryogenesis. Biolistic transfection will facilitate experimental strategies in Ascaris embryos complementing other biochemical tools available (e.g., in vitro whole-cell embryo extracts for transcription, RNA processing, and translation). Transfection experiments with adult schistosomes further suggest that the biolistic strategy should be applicable to a variety of other parasitic helminths. The development of these methods provides molecular genetic tools to study gene expression and the biology of a variety of types and developmental stages of important helminth parasites.

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]

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.