Activity-Dependent Changes in Rat Ventral Horn Neurons in vitro; Summation of Prolonged Afferent Evoked Postsynaptic Depolarizations Produce a d-2-Amino-5-Phosphonovaleric Acid Sensitive Windup

Eur J Neurosci. 1990;2(7):638-49. doi: 10.1111/j.1460-9568.1990.tb00453.x.

Abstract

The synaptic responses of lumbar ventral horn neurons including identified flexor motoneurons, to graded stimulation of peripheral nerves have been recorded in vitro in the young rat spinal cord-hindlimb preparation. Single shock stimulation of low threshold myelinated afferents evoked short latency (< 20 ms) short duration (< 1.0 s, 391 +/- 42 ms n=43 SEM) compositive mono- and polysynaptic potentials. Recruitment of both thinly myelinated (A delta) and unmyelinated (C) afferent fibres elicited a prolonged postsynaptic depolarization (> 1 s) in all cells. In the majority of cells (67.4%), this depolarization exceeded 4.0 s in duration (8.01 +/- 0.4 s, n=26, maximum 14 s). In the remainder, shorter responses were evoked (< 3.0 s, mean=1.74 +/- 0.4 s, n=18). In those cells where the postsynaptic response to a single A delta or C fibre strength stimulus exceeded 4 s, low frequency (0.5 - 1.0 Hz) repetitive stimulation resulted in a temporal summation of the postsynaptic depolarizations, which generated a cumulatively increasing depolarization. This incrementing depolarization was sufficient in 33% of the cells to produce a progressive increase in spike discharge (windup). On cessation of the train of stimuli the depolarization decayed slowly (65 +/- 27 s). The N-methyl d-aspartic acid (NMDA) receptor antagonist d-2-amino-5-phosphonovaleric acid (d-APV) reduced the duration and amplitude of the prolonged postsynaptic depolarizations elicited by a single shock stimulation of small diameter afferents by 57% and 50% respectively. A smaller effect was produced on the low threshold afferent evoked early excitatory postsynaptic potentials (EPSP) (3% decrease in amplitude and 24% decrease in duration). In the presence of d-APV the cumulatively incrementing depolarization produced by repetitive stimulation was substantially reduced and windup failed to occur. Activity-dependent amplifications of primary afferent evoked responses in spinal neurons therefore involves a temporal summation of d-APV sensitive prolonged postsynaptic depolarizations.