Intensity discrimination deficits cause habituation changes in middle-aged Caenorhabditis elegans Tiffany A. Timbers a,1 , Andrew C. Giles a,1 , Evan L. Ardiel a , Rex A. Kerr b , Catharine H. Rankin c, * a Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada b Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, VA, USA c Brain Research Centre and Department of Psychology, University of British Columbia, Vancouver, British Columbia, Canada Received 14 January 2012; received in revised form 31 March 2012; accepted 31 March 2012 Abstract The ability to learn and remember is critical for all animals to survive in the ever-changing environment. As we age, many of our biological faculties decay and of these, decline in learning and memory can be the most distressing. To carefully define age-dependent changes in learning during reproductive age in the nematode Caenorhabditis elegans, we performed a parametric behavioral study of habituation to nonlocalized mechanical stimuli (petri plate taps) over a range of intensities in middle-aged worms. We found that as worms age (from the onset of reproduction to the end of egg laying), response probability habituation increases (at both 10- and 60-second interstimulus intervals) and that these age-related changes were associated with a decrease in the discrimination between stimuli of different intensities. We also used optogenetics to investigate where these age-dependent changes occur. Our data suggest that the changes occur upstream of mechanosensory neuron depolarization. These data support the idea that declines in stimulus intensity discrimination abilities during aging may be one variable underlying age-related cognitive deficits. © 2013 Elsevier Inc. All rights reserved. Keywords: Learning; Habituation; Aging; C. elegans; Stimulus discrimination; Short-term memory 1. Introduction Our capacity to learn and remember declines naturally with age. Although many studies have examined changes in learning and memory related to early development or old age, aging-related changes during early and middle adult- hood have been understudied (Alwin and Hofer, 2011). In aging studies, reproductive and middle-aged subjects are often pooled and compared with geriatric cohorts, poten- tially masking or diminishing any age-dependent changes within these groups. This common approach may explain why there is no consensus on when cognitive decline begins and why most treatments are targeted to individuals in late adulthood (60 –70 years old; discussed in Salthouse, 2009). Understanding the changes in the midlife years may lead to earlier interventions or treatments. Age-dependent changes in learning and memory are con- served across the animal kingdom. Thus, animal models can be used to gain insights into the natural aging process of cognitive decline and to develop new approaches for treat- ment. However, large parametric studies of aging and be- havior are expensive and difficult in humans and other mammals. In contrast, the model organism Caenorhabditis elegans, with a short life span (reaches reproductive matu- rity in the laboratory in 3 days), is an ideal model to study the relationship between aging and learning (both associa- tive and nonassociative) (Beck and Rankin, 1993; Kauff- man et al., 2010; Murakami et al., 2005; Murakami and Murakami, 2005). * Corresponding author at: Brain Research Centre and Department of Psychology, University of British Columbia, 2136 West Mall, Vancouver, British Columbia, Canada V6T 1Z4. Tel.: +1 604 822 5449; fax: +1 604 822 7299. E-mail address: crankin@psych.ubc.ca (C.H. Rankin). 1 Both authors contributed equally to this manuscript. Neurobiology of Aging 34 (2013) 621– 631 www.elsevier.com/locate/neuaging 0197-4580/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.neurobiolaging.2012.03.016