P J Harrison

The contribution of ischaemia and deformation to the conduction block generated by compression of the cat sciatic nerve

The pattern of conduction block induced in cat peripheral nerve by compression has been investigated electrophysiologically by recording unitary action potentials. A degree of compression, associated with chronic compression disorders in man, was applied to the cat sciatic nerve and resulted in a conduction block typified by early failure of the slow conducting myelinated axons. By contrast, a greater degree of compression, a degree more likely to result in acute compression lesions, produced a different pattern of effect, inducing early conduction failure in the fast conducting myelinated axons. These results are related to earlier studies which have shown that nerve deformation during compression has a differential action upon fast myelinated axons, while nerve ischaemia has a differential action upon slow myelinated axons.

The dorsal column projection of muscle afferent fibres from the cat hindlimb.

1. The extent of the projection of hindlimb muscle afferent fibres ascending the dorsal columns has been studied in barbiturate‐anaesthetized cats. This has been investigated using electrical stimulation of the dorsal columns at different spinal levels while recording from (i) peripheral muscle nerves, and (ii) single muscle afferent fibres within the dorsal columns. These two approaches have produced complementary results. 2. The conduction velocity of both group I and group II afferent fibres decreased progressively after entering the dorsal columns. 3. The majority of group I and group II fibres project at least as far as L2 but leave the dorsal columns at or before the lower thoracic segments. 4. By taking advantage of the lower electrical threshold of Ia compared to Ib fibres in the hamstring nerves, it could be shown that both Ia and Ib fibres leave the dorsal columns at similar locations. 5. A small number of afferent fibres were found to project to C1. On the basis of previous work it is likely that such fibres originate from Pacinian or paciniform corpuscles.

The effects of compression upon conduction in myelinated axons of the isolated frog sciatic nerve.

1. Action potential conduction along frog sciatic nerve fibres has been monitored during compression of a mid‐portion of the nerve. 2. The effects of compressing a 24 mm length of nerve with a pressure of 250 mmHg applied pneumatically were investigated by recording unitary action potentials. A plot of time before conduction failure (survival time) against initial conduction velocity revealed that the faster myelinated axons tend to fail before the slower myelinated axons. A large degree of scatter was evident in the pooled data as well as in the data from individual experiments. 3. When the compression was made more severe by increasing the applied pressure to 750 mmHg, the order of block was reversed, i.e. the slower myelinated axons tended to block first. Similar scatter in the order of conduction block was observed. 4. The average survival time of units following application of compression was considerably different between these two series of experiments. When 750 mmHg pressure was applied, units survived for, on average, 10.9 min (n = 246). When 250 mmHg pressure was applied units survived for, on average, 50.4 min (n = 148). 5. The results are discussed in relation to the underlying causes of conduction failure as a result of compression and in relation to results from previous investigations.

Evidence for functional co-activation of N-methyl-D-aspartate receptors by glycine

The excitatory neurotransmitter glutamate acts at several receptor subtypes in the CNS, including N-methyl-D-aspartate (NMDA) receptors. The inhibitory neurotransmitter glycine is a co-agonist of NMDA receptors and functional glycinergic co-activation of NMDA receptors is theoretically possible due to the presence of background glutamate. We report the first high fidelity recording of a distinct NMDA receptor excitatory post-synaptic potential (EPSP) in the intact mammalian CNS. The EPSP was evoked by multi-shock activation of a glycinergic pathway rather than a glutamatergic pathway and had characteristics most compatible with glycine, rather than glutamate, activation of NMDA receptors.

The relationship between ischaemic conduction failure and conduction velocity in cat myelinated axons

Unitary action potentials have been recorded from cat spinal root filaments following electrical stimulation of hindlimb peripheral nerves. Potentials were monitored both before the ischaemia which follows the onset of cardiac arrest. The relationship between time to conduction failure (survival time) and initial conduction velocity was determined for 164 nerve fibres. This revealed that during ischaemia, slow myelinated axons tend to fail before fast myelinated axons. The average survival time was 24.6 min (range 11–39 min). The results are discussed in terms of (i) the possible mechanisms underlying ischaemic conduction block, (ii) their clinical implications for the role of ischaemia in peripheral neuropathies, and (iii) using ischaemia as an experimental technique to produce a differential nerve block.

Group II-activated lumbosacral interneurones with an ascending projection to midlumbar segments of the cat spinal cord.

1. In anaesthetized cats, single‐unit microelectrode recordings were made in the lateral funiculus at L6, from the axons of lumbosacral interneurones discharged by hindlimb group II muscle afferents. 2. The level of the ascending projection of these interneurones was investigated by antidromic activation of their axons in the lateral funiculus from different spinal levels. The majority of units encountered were found to have an ascending projection to at least the L4 level and, of these, most (85%) did not project beyond the L4 or L3 segments of the cord. 3. The axons studied were discharged by group II afferents primarily from knee extensor muscles. Some units were discharged in addition by cutaneous and/or joint afferents. 4. The implications of this ascending projection are discussed.

The variation in safety factor with myelinated axon diameter: experiments with low sodium perfusion

Theoretical considerations suggest that myelinated axons of a small diameter (and therefore with a low conduction velocity) also have a low safety factor. That these axons, many of which are involved in the mediation of pain, may fail first when action potential conduction is inhibited may explain the analgesic properties of local anesthetics. We have tested this hypothesis by perfusing frog myelinated axons with a low concentration of sodium ions and monitoring the reduction in conduction velocity, and the tendency to conduction failure. It was found that axons conducting action potentials at below 10 m/s are affected to the greatest extent by low sodium perfusion, indicating that slow conducting axons do have a low safety factor and confirming the earlier theoretical prediction.

The ascending projection of interneurones activated by group I muscle afferent fibres of the cat hindlimb.

1. The level of the ascending projection of lumbosacral interneurones with a monosynaptic input from group I muscle afferents of the cat hindlimb has been investigated. The study was concerned particularly with the interneurones mediating group I non‐reciprocal inhibition of motoneurones. 2. In chloralose‐anaesthetized cats, single‐unit microelectrode recordings were made, in the lateral funiculus at L6, from the ascending axons of lumbosacral interneurones. The axons studied were discharged by group I afferents primarily from extensor muscles of the knee and ankle. Some units were discharged in addition by cutaneous and/or joint afferents. 3. The extent of the ascending projection of the interneurones was assessed by antidromic activation of their axons in the lateral funiculus at different spinal levels. The great majority of axons tested (thirty‐four out of thirty‐six) were found to have an ascending projection to at least the L4 level and of these most (90%) did not project beyond the L4 or L3 segments of the cord. 4. The projection to at least L4, together with monosynaptic input from group I afferents and a pattern of peripheral input characteristic of interneurones in laminae V‐VI of lumbosacral segments, identified thirty‐four of the thirty‐six units as interneurones mediating group I non‐reciprocal inhibition. 5. These results suggest that the ascending group I inhibitory pathway, formed by these interneurones, is associated specifically with the group I relay of the dorsal spinocerebellar tract in Clarkes column, rather than being conterminous with group I afferents, which project throughout the rostral lumbar and lowest thoracic segments.

A group II-activated ascending tract of lumbosacral origin in the cat spinal cord.

1. Electrophysiological investigations have revealed a population of ascending tract neurones originating in the lumbosacral enlargement, with input from group II muscle afferents of the cat hindlimb. 2. Single‐unit microelectrode recordings were made in the lateral funiculus at L6, from the axons of thirty‐four ascending tract neurones. All of the axons were antidromically activated by stimulation of the ipsilateral lateral funiculus at Th13 and, whenever tested (eight units), at C1. 3. Conduction velocities of the axons, between the L6 and Th13 segment, ranged from 33 to 92 m s‐1 (mean 61 m s‐1). 4. All of the ascending tract neurones were discharged following electrical stimulation of muscle nerves at group II strength, but not by weaker stimuli in the group I range. Most of the investigated neurones were excited by group II afferents of more than one muscle nerve. In addition, a proportion of the units tested could also be discharged by cutaneous and by joint afferents. 5. Responses to natural stimuli were investigated in eighteen ascending tract neurones discharged by electrical stimulation of group II afferents in the gastrocnemius‐soleus (GS) and plantaris (P1) nerves which were dissected free in continuity with their muscles. Seven units were spontaneously active. Eight units responded to isometric contraction of the GS/P1 muscles with a discharge occurring mainly on the falling phase of muscle tension. Nine units increased their discharge frequency in response to stretching of the muscles and five units responded to mechanically probing the muscles with a blunt instrument. 6. The final termination sites of this group of ascending tract neurones has yet to be determined. Initial attempts (three units) to antidromically activate the neurones from the cerebellum have been unsuccessful. Other likely areas of termination in the brain stem are considered.