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

1460-9568

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

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.

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