Paired pulse stimulation of perforant pathway evokes a triphasic (early paired pulse inhibition (ePPI), paired pulse facilitation (PPF) and late PPI (lPPI) response in the dentate gyrus (DG). The ePPI is modulated by activation of GABAB receptors (Canning & Leung, 2000). We have revalidated this modulation and then investigated whether nicotinic receptors are also involved in this paired pulse paradigm.
Male Sprague-Dawley (SD) rats (body weight 250-350 g) were anaesthetized with urethane (1.25 mg kg-1, I.P.). All animals were humanely killed at the end of the experiments. The lateral tail vein was cannulated for drug administration, and the femoral artery was cannulated for blood pressure monitoring. Body temperature was maintained at 37 ± 10 °C by a homeothermic heat pad. Field excitatory postsynaptic potentials (fEPSPs) and population spikes (PS) were evoked in the DG by bipolar stimulation of the perforant pathway and recorded using a glass electrode (filled with 2 % Pontamine sky blue in 2 M NaCl with an in vitro impedance of 2.5-3.0 mV). PS amplitude was used as a measure of DG granule cell excitability. Experiments were carried out at 70 % of the maximum PS amplitude. PPI/PPF was evoked with an inter-pulse interval (IPI) between 20 and 1000 ms.
Baclofen (0.03-3 mg kg-1, I.V. n = 2-6), a GABAB receptor-selective agonist, dose dependently inhibited both ePPI and PPF but not lPPI. This inhibition was prevented by CGP35348 (200 mg kg-1, I.V. n = 6), a selective GABAB antagonist. TC2559 (2 mg kg-1, I.V. n = 6), an α4β2-selective partial agonist, reversibly, repeatedly and differentially affected ePPI, lPPI and PPF in DG. The ePPI was significantly (P < 0.01, Student’s paired t test) inhibited by TC2559, at an IPI of 25 ms, from a control of 57.5 ± 4.4 % (mean ± S.E.M.) to 36.4 ± 4.8 %. In contrast, the PPF and lPPI were all significantly (P < 0.05) enhanced, from 4.0 ± 6.3 % to 69.7 ± 17.2 % (IPI of 90 ms) for PPF and from 16.6 ± 2.8 % to 42.5 ± 4.6 % (IPI of 500 ms) for lPPI, respectively. DHβE (1 mg kg-1, I.V. n = 6), an α4β2-preferring antagonist, fully reversed the TC2559 effect on PPF and lPPI, but only partially on ePPI.
In conclusion, stimulation of α4β2 nicotinic receptors can modulate the DG paired pulse index. This modulation may contribute to nicotinic facilitation of the short-term neuronal plasticity in DG.