Behavioral decay in aging male C. elegans correlates with increased cell excitability

Department of Biology, Texas A&M University, 3258 TAMU, College Station, TX 77843-3258, USA.
Neurobiology of aging (Impact Factor: 5.01). 01/2012; 33(7):1483.e5-23. DOI: 10.1016/j.neurobiolaging.2011.12.016
Source: PubMed


Deteriorative changes in behavioral functions are natural processes that accompany aging. In advanced aged C. elegans nematodes, gross decline in general behaviors, such as locomotion and feeding, is correlated with degeneration of muscle structure and contractile function. In this study, we characterized the age-related changes in C. elegans male mating behavior to determine possible causes that ultimately lead to age-related muscle frailty. Unlike the kinetics of general behavioral decline, we found that mating behavior deteriorates early in adulthood, with no obvious muscle fiber disorganization or sperm dysfunction. Through direct mating behavior observations, Ca(2+) imaging, and pharmacological tests, we found that the muscular components used for mating become more excitable as the males age. Interestingly, manipulating either the expression of acetylcholine receptor (AChR) genes or dietary-mediated ether-a-go-go family K(+) channel function can reduce the muscle excitability of older males and concurrently improve mating behavior, suggesting a correlation between these biological processes.

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    • "Until recently, it was thought that C. elegans neurons did not show age-related morphological decline at either a cellular or subcellular level, because while other tissues, such as skin and muscle, deteriorate with age (Garigan et al., 2002), neurons remained surprisingly intact (Herndon et al., 2002). These data seem counterintuitive, considering multiple sensory behaviors as well as motility decline with age in C. elegans (Glenn et al., 2004; Murakami et al., 2005; Hsu et al., 2009; Kauffman et al., 2010; Guo et al., 2012) and changes in dendritic spines and synapse number with age have been observed in other organisms, including non-human primates and rats (reviewed in Burke and Barnes, 2006; Morrison and Baxter , 2012). Due to this incongruity, recent work has again tested the integrity of neurons and found that while neuronal cell bodies stay intact, neuronal processes, subcellular structures (Pan et al., 2011; Tank et al., 2011; Toth et al., 2012), and neuronal activity (Chokshi et al., 2010; Mulcahy et al., 2012) all show age-dependent changes. "
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    ABSTRACT: Our understanding of the molecular and genetic regulation of aging and longevity has been greatly augmented through studies using the small model system, C. elegans. It is important to test whether mutations that result in a longer life span also extend the health span of the organism, rather than simply prolonging an aged state. C. elegans can learn and remember both associated and non-associated stimuli, and many of these learning and memory paradigms are subject to regulation by longevity pathways. One of the more distressing results of aging is cognitive decline, and while no gross physical defects in C. elegans sensory neurons have been identified, the organism does lose the ability to perform both simple and complex learned behaviors with age. Here we review what is known about the effects of longevity pathways and the decline of these complex learned behaviors with age, and we highlight outstanding questions in the field.
    Frontiers in Genetics 11/2012; 3:259. DOI:10.3389/fgene.2012.00259
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    ABSTRACT: Frailty is a feature of neuromuscular ageing. Here we provide insight into the relative contribution of pre and postsynaptic dysfunction to neuromuscular ageing using the nematode Caenorhabditis elegans. Assays of C. elegans motility highlight a precipitous decline during ageing. We describe a novel deployment of pharmacological assays of C. elegans neuromuscular function to resolve pre and postsynaptic dysfunction that underpin this decreased motility during ageing. The cholinergic agonist levamisole and the cholinesterase inhibitor aldicarb elicited whole worm contraction and allowed a direct comparison of neuromuscular integrity, from 1 to 16 days old: Measurements could be made from aged worms that were otherwise almost completely immobile. The rapidity and magnitude of the drug-induced contraction provides a measure of neuromuscular signalling whilst the difference between levamisole and aldicarb highlights presynaptic effects. Presynaptic neuromuscular transmission increased between one and five days old in wild-type but not in the insulin/IGF1 receptor mutant daf-2 (e1370). Intriguingly, there was no evidence of a role for insulin-dependent effects in older worms. Notably in 16 day old worms, which were virtually devoid of spontaneous movement, the maximal contraction produced by both drugs was unchanged. Taken together the data support a maturation of presynaptic function and/or upstream elements during early ageing that is lost after genetic reduction of insulin signalling. Furthermore, this experimental approach has demonstrated a counterintuitive phenomenon: In aged worms neuromuscular strength is maintained despite the absence of motility.
    Journal of Experimental Biology 10/2012; 216(3). DOI:10.1242/jeb.068734 · 2.90 Impact Factor
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    ABSTRACT: Author Summary An animal's behavior is a complex output displayed in response to diverse external cues, which are sensed and processed by the nervous system. Nerve cells translate sensory information into chemical secretions (neurotransmitters). These chemical signals allow neurons and muscles to communicate and coordinate motor responses. However, it is complicated how these signals are interpreted in neuronal circuits to start, continue, modify, and end specific behaviors, under the appropriate conditions. The neurotransmitter dopamine (DA) is involved in adjusting animal movements, thus DA neurotransmission is a candidate for coupling behaviors to the proper situational context. Here, we used C. elegans copulation to understand the DA-regulated neuronal mechanisms that promote when and where motor responses should be executed. During mating, DA is used as a feedback mechanism to adjust the activity of multiple sensory-motor neurons and muscles that promote the rhythmic thrusting of the male copulatory organs against his partner's vulval genitalia. If vulval signals are withdrawn when the male loses contact with his mate's genitalia, the DA-adjusted motor neurons' activities dampen to cease cue-independent genital penetration attempts. Therefore, DA secretions fine-tune these motor outputs to be exclusively displayed at the vulva and thus confine a behavior to its corresponding context.
    PLoS Genetics 11/2012; 8(11):e1003015. DOI:10.1371/journal.pgen.1003015 · 7.53 Impact Factor
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