SMALL-CALIBER AFFERENT INPUTS PRODUCE A HETEROSYNAPTIC FACILITATION OF THE SYNAPTIC RESPONSES EVOKED BY PRIMARY AFFERENT A-FIBERS IN THE NEONATAL RAT SPINAL-CORD INVITRO

1. The effect of brief primary afferent inputs on the amplitude and du ration of the synaptic potentials evoked in ventral horn (VH) neurons by the activation of other unconditioned primary afferents was studied by current-clamp intracellular recording in the neonatal rat hemisect ed spinal cord in vitro. Low-frequency ( 1 Hz) trains of stimulation w ere applied to a lumbar dorsal root (Conditioning root) for 20-30 s. T est excitatory synaptic potentials (EPSPs) were evoked by single elect rical shocks applied to an adjacent Test dorsal root. 2. Test and Cond itioning inputs were generated at stimulation strengths sufficient to activate Abeta-, Adelta- and C-afferent fibers successively. At Adelta - and C-fiber strength the EPSPs lasted for 4-6 s, and, during the rep etitive Conditioning inputs, these summated to produce a progressively incrementing cumulative depolarization that slowly decayed back to th e control V(m) over tens of seconds. 3. Dorsal root conditioning produ ced heterosynaptic facilitation, defined as an enhancement of Test EPS Ps above their DC matched controls, in 7 out of 20 neurons. To facilit ate the unconditioned afferent input, the intensity of conditioning st imulation had to exceed the threshold for the activation of thin myeli nated (Adelta) afferents: conditioning at Abeta-fiber strength had no effect, whereas Adelta- and C-fiber strength conditioning were equally effective. 4. Heterosynaptic facilitation of only Abeta- or Adelta-fi ber-evoked Test EPSPs was observed, no enhancement of C-fiber strength Test EPSPs could be demonstrated. The facilitation manifested as incr eases in the EPSP peak amplitude, area or the number of action potenti als evoked. 5. Conditioning trials that produced heterosynaptic facili tation generated cumulative depolarizations larger than those produced by ineffective conditioning trials (9.1 +/- 3.1 vs. 3.3. +/- 0.5 mV a fter 20 s conditioning at resting V(m), mean +/- SE, n = 6 and 13, res pectively; P < 0.05). The slope of the V(m) trajectory during the summ ation of the conditioning EPSPs was higher in trials resulting in hete rosynaptic facilitation, at 0.31 +/- 0. 10 mV/s in neurons with hetero synaptic facilitation and 0.06 +/- 0.02 mV/s in cells without heterosy naptic facilitation (P < 0.05). 5. Four of the 20 VH neurons in our sa mple responded to Adelta/C-fiber conditioning with action-potential wi ndup: all 4 also displayed heterosynaptic facilitation. 6. Heterosynap tic facilitation decayed after the completion of the conditioning stim ulus with a time course that was parallel to but not superimposable on that of the slow V(m) depolarization evoked by the conditioning. The duration of Test EPSP facilitation varied between 45 and 180 s. 7. Rep etitive stimulation of thin myelinated and unmyelinated primary affere nts, even for short periods at a low frequency, enhanced neuronal resp onses to low-intensity stimulation of unconditioned inputs. This heter osynaptic facilitation has features in common with the central sensiti zation of spinal neurons that contributes to postinjury pain hypersens itivity. Further investigation into the cellular mechanisms of heteros ynaptic facilitation will contribute to the understanding of use-depen dent synaptic plasticity in the spinal cord and its involvement in sen sory disturbances.