Murakami, S. (2011) International Worm Meeting "Clarifying misconceptions about age-related memory impairment (AMI)."

Murakami, S.

[International Worm Meeting, 2011]

Age-related memory impairment (AMI) includes mild impairment of the ability to learn new information and to recall previously learned information. The term, age-associated cognitive impairment (AACI), is also used to describe memory impairment during aging. We define AMI (or AAMI) as memory impairment in comparison with young normal controls (young v.s. old comparison); and AACI as in comparison with age-matched normal counterparts (non-AMI v.s. AMI comparison at the same age) (1). We prefer using AMI over AAMI, since AAMI is often confused with the transition state, MCI. Here we clarify some misconceptions we encountered through scientific communication. Firstly, AMI is not a simple decrease in learning and memory. Recent studies suggest that aging causes not only declines but also increases of learning and memory. AMI is not a gradual decay but rather an aspect of age-related alterations in the nervous functions. Importantly, neural loss plays a minor role in AMI. Secondly, AMI is not a disease. AMI is a normal state prior to the disease state. What distinguishes AMI from dementia besides cognitive deficits? A few lines of evidence analysis in humans suggest that reduced metabolic activity may be a hallmark of AMI in humans. Finally, AMI cannot be independent of aging. There is an argument that aging should be separated from AMI. However, aging affects learning and memory, which results in AMI. More precisely, AMI is caused by age-related processes that affect learning and memory. The age-related processes should include age-related changes in neurons as well as elsewhere, including modifiers and pathways for learning and memory. In fact, a type of AMI can be suppressed by serotonin inhibitors, which are good examples for such modifiers. It is unlikely that aging neurons are the sole cause of AMI. Thus, focusing only on neurons would miss important aspects of the mechanisms for AMI. Although the study of aging neurons has been emphasized, it is equally essential to investigate the aging processes. More details are discussed in Ref. 1. The abstract may be presented with the other presentation. Reference: 1. Murakami, S., Cabana, K., Anderson, D. Current advances in the study of oxidative stress and age-related memory impairment in C. elegans. John Wiley & Sons, Hoboken, NJ. In Press.

Nektarios Tavernarakis et al. (2001) International C. elegans Meeting "Functional analysis of the complete DEG/ENaC family of ion channel proteins of C. elegans"

Nektarios Tavernarakis, Beate Gerstbrein, Ami Modi, Monica Driscoll

[International C. elegans Meeting, 2001]

mec-4 and mec-10 encode ion channel subunits of the DEG/ENaC family of proteins. Importantly, MEC-4 and MEC-10 are postulated to be the core subunits of the mechanosensory channel in the six touch receptor neurons. This is an exciting working hypothesis since channels specialized for mechanotransduction have eluded cloning efforts for years. Thus analysis of this channel family is of profound interest in a little understood area of signal transduction. Because the genes encoding these proteins can mutate to cause neurodegeneration the proteins were originally named degenerins. The database compiled by the C. elegans Genome Sequencing Consortium includes a total of 23 additional degenerin-related genes. Our characterization of these genes has led the determination of the expression pattern of all previously uncharacterized degenerins. This analysis revealed that members of the degenerin family function in a variety of cell types ranging from neurons to muscles and epithelia. Some of these degenerin-like genes are expressed in nose touch neurons and could thus be candidates for the elusive mechanosensory channel in those cells. In support of this notion, dsRNA mediated interference with the expression of these degenerins largely decreases the response to nose touch. In addition, we have found degenerin-like genes to be expressed in body touch neurons and motorneurons of the ventral nerve cord where they could co-assemble with known degenerins to mediate the mechanosensory properties of these cells. Specific degenerins are expressed in and are needed for the normal function of the excretory canal cell, which, in the nematode, is the functional equivalent of the kidney. It is intriguing that in mammals, the degenerin-homologous ENaCs function in this organ to regulate electrolyte balance. We will present detailed expression patterns and functional characterization at the meeting. Our observations indicate, that contrary to what might be expected for such a multi-gene family, members of the degenerin group, closely related in sequence, are not functionally redundant. In an effort to assign degenerin genes to known genetic loci, we are currently attempting to complement closely linked candidate mutations and we are also screening deletion libraries for null alleles.

Turek M et al. (2015) J Vis Exp "Agarose Microchambers for Long-term Calcium Imaging of Caenorhabditis elegans."

Bringmann H, Turek M, Besseling J

[J Vis Exp, 2015]

Behavior is controlled by the nervous system. Calcium imaging is a straightforward method in the transparent nematode Caenorhabditis elegans to measure the activity of neurons during various behaviors. To correlate neural activity with behavior, the animal should not be immobilized but should be able to move. Many behavioral changes occur during long time scales and require recording over many hours of behavior. This also makes it necessary to culture the worms in the presence of food. How can worms be cultured and their neural activity imaged over long time scales? Agarose Microchamber Imaging (AMI) was previously developed to culture and observe small larvae and has now been adapted to study all life stages from early L1 until the adult stage of C. elegans. AMI can be performed on various life stages of C. elegans. Long-term calcium imaging is achieved without immobilizing the animals by using short externally triggered exposures combined with an electron multiplying charge-coupled device (EMCCD) camera recording. Zooming out or scanning can scale up this method to image up to 40 worms in parallel. Thus, a method is described to image behavior and neural activity over long time scales in all life stages of C. elegans.