Synapse specific changes in serotonin signalling contribute to age-related changes in the feeding behaviour of the pond snail, Lymnaea

Mark Yeoman1, Bhavik Patel2, Martin Arundell2, Danny O’Hare2
1University of Brighton, Brighton, United Kingdom, 2Imperial College, London, United Kingdom

Ageing is associated with changes in the synaptic efficacy of connections within the CNS, although why some synapses are affected by age while others appear to maintain function is far from clear. Using the relatively simple neuronal network that controls feeding behaviour in the pond snail Lymnaea, this study examined the contribution that alterations in serotonergic signalling make to age-related changes in motor function. Ageing was associated with a decrease in the frequency of repetitive sucrose-evoked feeding movements (p<0.01, ANOVA) due to selective increases in the duration of the inter-bite interval (p<0.01; swallow phase), with no change in the bite duration (protraction/rasp phases) of each feeding cycle (Arundell et al. 2006). HPLC analysis of the buccal ganglia, demonstrated an age-related decrease in 5-HIAA levels that was positively correlated with the feeding frequency (p<0.01) and negatively correlated with the duration of the inter-bite interval (p<0.05), indicating that changes in serotonergic signalling were involved in determining the aged phenotype. Serotonin released from the cerebral giant cells regulates neurones controlling all three phases of the rhythm (McCrohan et al. 1980). To investigate why age selectively targeted the swallow phase neurones we compared changes in the serotonergic signalling at the synapse between the CGCs and a B1 protraction phase motor neuron to signalling between the CGC and the B4 swallow phase motor neuron. The postsynaptic actions of 5-HT were examined using two key motor neurons that are monosynaptically excited by the CGCs. Application of 5-HT to B1 (protraction phase) motor neurons caused a concentration dependent increase in the amplitude of the evoked depolarisation, which was significantly greater in the old neurones compared to both young or middle aged (F(2,80) =21.75; p<0.001; 2-way ANOVA). Conversely, the amplitude of the 5-HT-induced depolarisation in the B4 (swallow phase) motor neuron, and the ability of 5-HT to induce conditional bursting in B4 cells were attenuated in the old neurones (F(2,80) =7.44; p<0.01 and F(2,80)=7.20; p<0.01, respectively; 2-way ANOVA). Both these functions are critical in allowing a full feeding rhythm. Pharmacological analysis of the serotonergic receptors on the B1 and B4 motor neurons showed that the ability of the CGC to excite B1 could be blocked by the 5-HT2 antagonist cinanserin (10-4M, p<0.001; t-test) and not by the mixed 5-HT1/2 antagonist methysergide (10-4M). However, the ability of the CGC to excite B4 was inhibited significantly by methysergide (Straub et al. 2007), while cinanserin was only capable of blocking the late component of the excitation (p<0.001, t-test), suggesting that the effects of age may be receptor specific.

In summary these data suggest that in Lymnaea, synapse-specific ageing maybe dependent on the complement of postsynaptic serotonergic receptors or their associated transduction mechanisms. Specifically, 5-HT1 receptors appear sensitive to age while 5-HT2 receptors appear protected.

References

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

2. McCrohan C.R. et al. J Exp Biol. 85:169-86, 1980.

3. Straub VA et al. J. Neurophysiol. 97(2):1088-99, 2007