FIGURE 15.

Effects of anti-amphiphysin antibodies on spinal inhibitory pathways. A: spinal reflex pathways of antagonistic muscle groups: afferent fibers project to Ia interneurons (gray) mediating disynaptic reciprocal inhibition (recurrent inhibition by glycinergic transmission) onto motor neurons (MN) supplying antagonistic muscle groups. In addition, afferents also project to local interneurons via polysynaptic transmission. Last-order interneurons (black) mediate primary afferent depolarization (PAD) of afferent fibers by activation of GABAa receptors (axo-axonal synapses; presynaptic inhibition). B: examples of Hofmann (H)-reflex recording at higher frequency (10 Hz) after stimulation of a peripheral (tibial) nerve in rats. The first deflection is the anterograde muscle response (M), the second response is the H-reflex after monosynaptic transmission in the spinal cord. In normal conditions, the H-reflex is fully suppressed at high-frequency simulation (green trace). Note that upon long-term intrathecal application of human anti-amphiphysin antibodies, the suppression of the H-reflex is insufficient (red trace). C: H-reflex recordings after tibial nerve stimulation together with stimulation of a nerve supplying antagonistic muscles (peroneal nerve). Top trace shows simultaneous stimulation, and bottom trace represents recordings with a 50 ms preceding volley of peroneal nerve stimulation resulting in reduction of H-reflex amplitude (green traces). In rats with intrathecal application of anti-amphiphysin antibodies (red trace), GABAergic presynaptic inhibition is reduced as shown by absent H-reflex depression after heteronymous stimulation. D: time course of H-reflex inhibition after heteronymous stimulation. Depression of the H-reflex is most pronounced at interstimulus intervals (delay) of 25–100 ms demonstrating polysynaptic mechanisms of presynaptic inhibition. In rats with application of anti-amphiphysin antibodies, H-reflex inhibition is absent. E and F: determination of presynaptic inhibition by in vivo recording of dorsal root potentials (dorsal root L5 is cut on one side and afferent volleys are delivered by tibial nerve stimulation). Dorsal root potentials (long-lasting upward deflection as shown in F) are mediated by presynaptic GABAergic inhibition due to primary afferent depolarization. Dorsal root potential amplitude is severely reduced in rats after intrathecal treatment with anti-amphiphysin antibodies. [From Geis et al. (103), by permission of Oxford University Press.]