LONG-TERM POTENTIATION IN AN ISOLATED PERIPHERAL NERVE-SPINAL CORD PREPARATION

1. Long-lasting increases in synaptic efficacy following repetitive st imulation have been demonstrated at several sites in the CNS, where th ey are collectively termed long-term potentiation (LTP). LTP is of int erest with respect to its presumptive relationship to learning and mem ory in hippocampus. In the spinal cord in vivo, an LTP-Like phenomenon is thought to underlie the allodynia and hyperalgesia that follows so me peripheral injuries. 2. We investigated the capacity of the isolate d neonatal rat spinal cord to sustain a long-lasting increase in a noc iceptive-related slow ventral root potential (sVRP) recorded from a lu mbar root after a tetanic train of stimuli to the peripheral cutaneous saphenous nerve. Stimuli were delivered at a low constant (0.02 s(-1) ) frequency during a 30-min control period. A tetanic stimulus train ( 10 s(-1) for 60 s) was then given followed by a resumption of low (0.0 2 s(-1)) frequency stimulation. Potentiation was defined as an increas e in sVRP area >2 SD above control mean. 3. Twenty of 20 preparations showed immediate posttetanic potentiation. In 13 of the 20, potentiati on was maintained for greater than or equal to 1 h after the tetanic s timulus train. 4. Potentiation was dependent on activation of C fibers during the inducing train; stimuli below C-fiber threshold, activatin g only A fibers, were ineffective. Potentiation was selectively expres sed by a long-latency component of the sVRP elicited by stimuli at a s trength that evoked both A-and C-fiber responses in the nerve. Shorter duration components elicited by A-fiber strength stimuli and sensitiv e to the lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA )/kainate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) did n ot potentiate. 5. The N-methyl-D-aspartate (NMDA) receptor antagonist (DL)-AP-5 reduced sVRP area by as much as 65%; 80 mu M was the maximal ly effective concentration. When AP-5 (80 mu M) was applied during the inducing train and then washed out, seven of eight preparations displ ayed LTP. The magnitude of potentiation (147.5 +/- 37.71% of control, mean +/- SD) was not different from that observed in untreated prepara tions. The region of the sVRP maximally depressed by AP-5 showed only transient potentiation after the tetanus. All the LTP of the total are a was contributed by longer-latency components. 6. The selective tachy kinin receptor antagonists RP 67,580 (NK1) and MEN 10,376 (NK2) each r educed sVRP area to similar to 85% of control. Neither antagonist prev ented LTP when applied during the inducing train. 7. The present resul ts demonstrate and characterize in preliminary fashion a form of LTP i n spinal cord. The LTP is dependent on C-fiber input both for inductio n and expression. It is apparently not dependent on NMDA receptors for induction or expression, or on tachykinin NK1 and NK2 receptors for i nduction. Calcium influx through voltage-dependent calcium channels is suggested as a possible mechanism for induction.