Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCA284

Poster Communications

Developmental role of sigma-1 receptor in the regulation of hippocampal- CA1 area activity and spatial learning

F. moradpour1, Y. Fathollahi2, N. Naghdi3

1. Physiology, Kermanshah University of Medical Sciences, Kermanshah, Iran (the Islamic Republic of). 2. Physiology, Tarbiat Modares University, Tehran, Iran (the Islamic Republic of). 3. Physiology & Pharmacology, Pasteur Institute of Iran, Tehran, Iran (the Islamic Republic of).

Long term potentiation (LTP) has been suggested as a cellular mechanism of learning and memory. NMDA receptors (NMDAR) and non-NMDA receptors (nNMDAR) dependent mechanism has proposed as molecular bases of LTP. Among non-NMDAR dependent mechanisms, sigma 1 receptor has a potential to be the molecular bases of gonadal steroids effect on spatial memory and LTP during adolescence. Field potential recording (in vitro) from CA1 area of hippocampus is used to evaluate the effect of castration and BD107 (20 μM), a sigma-1 receptor antagonist, on synaptic plasticity and water maze is used to study spatial memory. Castration or hippocampal bilateral cannulations were done under 25 mg/kg Xylazine and 75 mg/kg Ketamine anesthesia. All procedures were done according international animal care and use program and supervised by Kermanshah University of Medical Sciences animal welfare and use committee. Three-way, two-way and one way ANOVA were used for statistical analysis. P-value was corrected using Holm-Bonferroni method to avoid Familywise error rate. Data are presented as mean ± SEM. Castration caused a reduction in the magnitude of both field excitatory postsynaptic potential-long term potentiation (fEPSP-LTP) (167.25 ± 8.85% vs. 124.46 ± 6.44%: Both n=6; P < 0.05) and population spike (PS)-LTP (307.26 ± 25.2% vs. 172.58 ± 14.74%: both n =6; P < 0.01) at 35d. BD-1047 reduced PS-LTP in sham-castrated rats (307.26 ± 25.2%; n=6 vs. 182.14 ± 27.61%; n=5; P < 0.05), whereas BD-1047 reversed the effect of castration on fEPSP-LTP (167.25 ± 8.85%; n=6 vs. 172.63 ± 9.70%; n =5; P > 0.5) at 35d. Castration had no effect on fEPSP-LTP (137.13 ± 8.85% vs. 139.22 ± 7.05%; n =5; P>0.5), but reduced PS-LTP (218.10 ± 23.33% vs. 157.09 ± 15.92%; n=5; P<0.01) at 60d. BD1047 increased the magnitude of fEPSP-LTP (139.22 ± 7.05% vs. 157.42 ± 7.05%: n=5; P<0.5), whereas had no effect on PS-LTP (157.09 ± 15.92% vs. 169.62 ± 17.44%: n=5; P<0.05), in castrated rats at 60d. In addition the results showed that sham-operated rats treated with BD-1047 took longer to locate the hidden platform during block 3 (P = 0.014) and block 4 (P = 0.015) only at 60d. But in castrates, the BD-1047-treated rats took longer to locate the hidden platform during block 3 (P = 0.053) and block 4 (P = 0.005) castrated rats at 35d and during block 3 (P = 0.014) and block 4 (P = 0.011) at 60d. This study shows that the σ1 receptors play a role in the regulation of both CA1 synaptic efficacy and neural plasticity dependent rat behavior (spatial learning ability). The regulatory role of σ1 receptors in activity-dependent CA1-LTP is locality- and age- dependent, whereas its role in spatial learning ability is age-dependent only. However the role of sigma-1 receptor on spatial learning and CA1 area plasticity might be modulated by gonads.

Where applicable, experiments conform with Society ethical requirements