Long-term potentiation and its neurotrophin-dependent modulation in the superior cervical ganglion of the rat are influenced by KCNQ channel function.

Ganglionic long-term potentiation (gLTP) in the rat superior cervical ganglion (SCG) is differentially modulated by neurotrophic factors (Nts): brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). KCNQ/M channels, key regulators of neuronal excitability, and firing pattern are modulated by Nts; therefore, they might contribute to gLTP expression and to the Nts-dependent modulation of gLTP. In the SCG of rats, we characterized the presence of the KCNQ2 isoform and the effects of opposite KCNQ/M channel modulators on gLTP in control condition and under Nts modulation. Immunohistochemical and reverse transcriptase polymerase chain reaction analyses showed the expression of the KCNQ2 isoform. We found that 1 µmol/L XE991, a channel inhibitor, significantly reduced gLTP (∼50%), whereas 5 µmol/L flupirtine, a channel activator, significantly increased gLTP (1.3- to 1.7-fold). Both modulators counterbalanced the effects of the Nts on gLTP. Data suggest that KCNQ/M channels are likely involved in gLTP expression and in the modulation exerted by BDNF and NGF.

Differential contribution of BDNF and NGF to long-term potentiation in the superior cervical ganglion of the rat.

Synaptic transmission in the sympathetic nervous system is a plastic process modulated by different factors. We characterized the effects of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) on basal transmission and ganglionic long-term potentiation (LTP) in the rat superior cervical ganglion. LTP was elicited by supramaximal tetanic stimulation (40 Hz, 3 s) of the sympathetic trunk and was quantified by measuring LTP decay time and LTP extent. Neurotrophins did not affect basal transmission, however, they differentially affected LTP. BDNF (200 ng/ml) increased LTP decay time and LTP extent 2.0-fold (p < 0.01). In contrast, NGF showed a dual effect: 200 ng/ml NGF reduced LTP decay time and LTP extent to 53% and to 32% of control value (p < 0.0001 and p < 0.02; respectively), whereas >350 ng/ml NGF significantly increased LTP decay time and LTP extent (p < 0.02). Digital analysis of compound action potentials suggests that neurotrophins could change the synchronization of unitary action potentials. Pharmacological data obtained in intact ganglia show that C2-ceramide produced a 2-fold enhancement in LTP, whereas tyrphostin AG879, an inhibitor of tyrosine kinase activity, reversed the NGF blockade and produced by itself an enhancement in LTP. In sliced ganglia we observed that an anti-TrkA antibody reversed the NGF-induced LTP blockade. Immunohistochemistry studies revealed that 83% of ganglionic neurons express TrkA, whereas 52% express p75 receptor, and 18% express TrkB receptor. We propose that p75 neurotrophin receptors and probably TrkB signaling enhance LTP, whereas TrkA signaling reduces it.