SERIAL E-M AND SIMULATION STUDY OF PRESYNAPTIC INHIBITION ALONG A GROUP IA COLLATERAL IN THE SPINAL-CORD

1. A muscle spindle primary afferent (group Ia) was physiologically id entified and labeled intracellularly with the use of horseradish perox idase (HRP) in the cat lumbar spinal cord. Serial-section electron mic roscopy (EM) was used to examine and reconstruct an entire axon collat eral and its branches within Clarke's column. In the present study the existence and location of presynaptic contacts on Ia afferent boutons along these collateral branches were determined from examination of t he serial-section electron-micrographs. 2. Of 36 Ia boutons examined i n serial sections along the branches of the same collateral, 3 presyna ptic contacts were found. Two of these contacts were made with Ia bout ons in a complex nodal region consisting of two unmyelinated side bran ches exhibiting a total of six Ia boutons. The other presynaptic conta ct was made with a Ia bouton in a nodal region consisting of two Ia bo utons connected by a thin unmyelinated bridge. 3. Computer simulations , based directly on the serial-section reconstructions, were used to i nvestigate the possible effects of these presynaptic contacts on membr ane potential and on a propagating action potential along the Ia colla teral. The effect of a presynaptic contact was modeled by a sustained gamma-aminobutyric acid-A (GABA(A))-activated chloride conductance. 4. The simulation results indicated that the effect of a presynaptic con tact on membrane potential and action-potential amplitude is likely to extend beyond the contacted bouton to other boutons occurring along t he short unmyelinated branches arising from the same node. However, de spite a large reduction of the action-potential amplitude within such a nodal region, the action potential was relatively unaffected at prio r and subsequent nodes along the myelinated collateral. 5. Simulations of action-potential generation, based on different densities of volta ge-dependent sodium and potassium conductances and the resting membran e leak conductance, indicated that a very large sustained chloride con ductance compared with known synaptically mediated GABA, conductances was required to significantly reduce the action-potential amplitude, i n agreement with a recent theoretical study on presynaptic inhibition by B. Graham and S. J. Redman. The possibility that presynaptic inhibi tion operates via a depolarization-induced inactivation of presynaptic calcium channels and the role of GABAB receptor activation is discuss ed.