| Abstract No.: | B-A2011 |
| Country: | Canada |
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| Title: | FRAGILE X MICE HAVE ENHANCED NICOTINIC CURRENTS LAYER VI PYRAMIDAL NEURONS DURING DEVELOPMENT |
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| Authors/Affiliations: | 1 Nyresa Alves*; 1 Evelyn Lambe; 1 Sameera Kassam;
1 University of Toronto, ON, Canada
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| Content: | We have previously demonstrated prominent nicotinic excitation of layer VI corticothalamic neurons in brain slices of rat prefrontal cortex. One potential mechanism of nicotinic receptor upregulation has been described through a pathway controlled by group I metabotropic glutamate receptors (Lin et al., 2002; Braunewell et al., 2003). To test this mechanism, we investigated nicotinic currents in a mouse model with enhanced group I metabotropic glutamate receptor signalling – the fragile X mouse – to see whether they would show elevated nicotinic currents in layer VI pyramidal neurons. Whole-cell voltage clamp and current-clamp recordings of layer VI pyramidal cells in the prefrontal cortex were used to observe cellular responses to acetylcholine while using atropine (200nM) and methyllycaconitine (10nM) to block muscarinic and α7 nicotinic currents respectively. Recordings were taken blind to the age and genotype of the animal and we found an enhancement of high-affinity nicotinic currents in fragile X mice during a crucial post-natal development period (p<0.05). In age-matched animals from postnatal days 7-25, average high-affinity nicotinic currents were 44.99 ± 5.43pA and 69.33 ± 9.64pA in fragile X mice. In both genotypes, the currents were found to be mediated directly by nicotinic receptors on the recorded layer VI neuron. The nicotinic currents were not significantly reduced by acute application of group I metabotropic glutamate receptors (MPEP [30 µM], CPCCOEt [100 µM]) in either the controls or the fragile X mice. This result suggests that nicotinic currents are indeed upregulated in fragile X mice. Thus, the fragile X mouse could provide a model for understanding the mechanisms involved in the upregulation of nicotinic receptors during the crucial developmental period. |
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