Age-related changes of a calcium-sensitive potassium channel in the Cerebral Giant Cells of the common pond snail Lymnaea stagnalis: its role in learning and memory

Greg Scutt, George Vaughan, Pratik Buhecha, Marcus Allen, Mark Yeoman
University of Brighton, Brighton, East Sussex, United Kingdom

We aim to use the relatively simple neuronal feeding network of the pond snail Lymnaea to investigate the role of the small-conductance, Ca2+-activated K+ channel (SK) in learning and memory, and understand how the activity of this channel changes with age. Using an associative conditioning paradigm, snails injected in vivo with the SK channel activator 1-ethyl-2-benzylimidizolinone (1-EBIO, 50 microlitres of 500 microMolar solution) demonstrated impaired learning compared with vehicle-injected controls (mean bites per animal over 2 mins in response to conditioned stimulus: 1-EBIO 1.19 + SEM 0.27 (n=12), control 16.08 +0.68 (n=11) p<0.0001). Intracellular recordings from spontaneously firing cerebral giant cells (CGCs, a pair of serotonergic cells that are integral to the neuronal feeding network and intimately involved in associative learning), showed that 1-EBIO delayed the recovery from individual action potentials (time to resting membrane potential following afterhyperpolarisation: 1micromolar 1-EBIO 0.528s +0.050s (n=5), control 0.320s +0.050s (n=5), p<0.02). Conversely, the SK inhibitor apamin, reduced recovery time from action potentials in spontaneously firing CGCs (time to resting membrane potential following afterhyperpolarisation: 1micromolar apamin 0.222s SEM+/- 0.014s (n=9), control 0.260s +0.008s (n=5), p<0.05). These results are coherent with the effect of ageing on the CGCs.1 Initial studies using two-electrode voltage clamp on these cells have identified a Ca2+-sensitive outward K+ current that increases with age (total charge carried by CdCl2 sensitive tail current: young 42.1 nC +30.9 nC (n=8), old 136.8 nC + 29.9 nC (n=8), p<0.03). This is consistent with results from previous studies using vertebrate models.2 Identifying a calcium-sensitive potassium channel that changes with age in an easily identifiable modulatory neurone crucial to the feeding network of Lymnaea, can help improve our understanding of how and why this channel undergoes age-related changes, and its corresponding role in learning and memory.

1. Arundell M et al. Neurobiol Aging 2006;27(12):1880-91

2. Hammond RS et al. J Neurosci 2006;26(6):1844-53