PubMed Health⌕ Search

Biomedical subjects

L M Mendell

Publications and source records attributed to L M Mendell.

85 records · Page 5Linked to original sources

Properties of synaptic linkage from long ranging afferents onto dorsal horn neurones in normal and deafferented cats.

1. In intact cats, dorsal horn cells sometimes respond to afferents entering the cord three or four segments more rostral. If dorsal roots near a segment have been cut for at least 4 weeks, many more cells respond to these long ranging afferents. Using extra- and intracellular recording, we examined the change in the nature of the connectivity of the long ranging afferents from dorsal roots L3 and L4 onto cells in L7. 2. In intact animals 33% of all cells in L7 recorded extracellularly and 48% of those recorded intracellularly exhibited responses to electrical stimulation of skin whose afferents entered the spinal cord over dorsal roots L3 and L4. Most of these responses had a long latency and followed high frequency stimulation poorly. 3. Thirty-eight to fifty-one days after cutting dorsal roots L5-S2, 76% of cells recorded intracellularly in L7 responded to long ranging afferents, in contrast to 48% in the intact cord. In these preparations 48% of all cells responded in less than 5 msec versus 12% in intact cats. Furthermore, 21% of the cells had natural receptive fields in the distant dermatome versus 1% in intact animals. 4. Chronic deafferentation of a segment increased the number of cells responding to afferents arriving over distal dorsal roots and increased the speed and power of the responses.

Action Potentials↗

A comparison of the reflex organization of thoracic and lumbar segments in the frog spinal cord.

Both lumbar dorsal root (DR) primary afferents and descending fibers in the lateral column (LC) make monosynaptic connections with ipsilateral lumbar motoneurons in the frog spinal cord. We have determined that LC fibers also make monosynaptic connections with thoracic motoneurons, while thoracic primary afferents do not. The central reflex time (CRT) for the lumbar DR-VR pathway was 2.5 +/- 0.3 msec, but the CRT for the thoracic DR-VR pathway was 8.5 +/- 2.6 msec. By using a conditioning-test paradigm we have been able to determine that the earliest sign of segmental synaptic transmission in thoracic motoneurons occurs only after a delay of 6.1 +/- 0.9 msec. These results correlate very well with the different morphological characteristics of lumbar and thoracic segments. We have also investigated the central organization of lumbar and thoracic segments and found that the segmental polysynaptic input to motoneurons is more diffuse in thoracic than in lumbar segments. The intersegmental reflexes between thoracic and lumbar segments provide additional evidence for a more diffuse organization in thoracic segments.

Animals↗

Alterations of synapses on axotomized motoneurones.

1. Properties of medial gastrocnemius motoneurones in cats were examined with intracellular electrodes 1-77 days after partial transection of the medial gastrocnemius muscle nerve. 2. Three sequential stages of reaction were defined: (i) firstly, conduction velocity of axotomized motoneurones fell, but e.p.s.p. properties and Ia-motoneurone connectivity were normal; (ii) secondly, e.p.s.p.s became characterized by prolonged rise times and half-widths and by diminished amplitudes; (iii) finally, failures of connectivity were also seen, that is, Ia spindle afferent fibres connected with fewer axotomized than normal homonymous motoneurones. 3. The reason for the change of e.p.s.p. properties cannot be stated with certainty: among the factors may be (i) a change of motoneurone membrane properties and morphology; (ii) partial detachment of synaptic boutons before their total disconnexion, and (iii) detachment of Ia afferent branches terminating on the motoneurone soma before those on the dendrites. 4. The previous conclusion that alteration of e.p.s.p. profiles following motoneurone axotomy was due to total disconnexion of those Ia fibres making synapses on the soma and proximal dendrites ("somatic stripping") must be modified to account for the findings that e.p.s.p. changes are seen before connectivity changes.

Animals↗

Analysis of pairs of individual Ia-E.P.S.P.S in single motoneurones.

1. Recordings of individual e.p.s.p.s evoked by the action of single medial gastrocnemius Ia fibres have been made from medial gastrocnemius motoneurones. In many motoneurones the action of two Ia fibres has been observed and the properties of the e.p.s.p.s compared. 2. For sixty-three pairs of averaged e.p.s.p.s, each from the same motoneurone, the ratio of half-widths was plotted against the ratio of rise times. These results were compared with theoretical values derived from the Rall compartmental model. It was found that variations in synaptic current time courses and differences in the termination of localized synaptic terminals were not sufficient to account for all the data. 3. Amplitude and rise time were inversely related but the correlation coefficient was very low. For pairs of e.p.s.p.s in the same motoneurone the e.p.s.p. with the fast rise time was larger than that with the slow rise time in forty-eight of sixty-three cases. 4. In a given motoneurone individual e.p.s.p.s evoked by the action of different Ia fibres did not vary greatly in amplitude. The ratio of peak amplitudes was less than 3 for 86% of the pairs of e.p.s.p.s examined, and the maximum was 4-8. 5. Amplitude histograms were constructed for individual e.p.s.p.s at thirty-three synapses. Twenty-two of them could be shown to satisfy the Poisson law. The others satisfied the binomial law or neither. 6. Within a given motoneurone the amplitude of an e.p.s.p. is closely related to the mean number of quanta released but not to the amplitude of the unit e.p.s.p. produced by the action of a single quantum of transmitter.

Animals↗

Individual EPSPs produced by single triceps surae Ia afferent fibers in homonymous and heteronymous motoneurons.

1. The individual EPSPs evoked by the action of single Ia fibers from cat triceps surae (MG, LG, SOL) were recorded in homonymous and heteronymous motoneurons innervating these same three muscles. 2. In general, Ia fibers projected to a greater percentage of homonymous than heteronymous motoneurons. One class of Ia afferent evoked EPSPs in virtually all homonymous motoneurons; the other had a substantially lower projection frequency. Possible difficulties introduced by the limited resolution of the averaging technique are discussed. 3. Individual EPSPs were larger on the average if evoked a) in SOL rather than in MG or LG motoneurons, b) by LG rather than by MG or SOL afferent fibers, or c) in homonymous rather than in heteronymous motoneurons. The mean EPSP was larger in homonymous than in heteronymous motoneurons because the largest EPSPs (greater than 150 muV) were found mainly in homonymous motoneurons. 4. Rise times of EPSPs were only slightly shorter in homonymous than in heteronymous motoneurons, suggesting that other factors besides relative location of Ia terminals account for the observed EPSP amplitude differences. Rise times in SOL motoneurons were longer than those in MG or LG. 5. LG afferent fibers tended to produce larger EPSPs in rostral than in caudal LG motoneurons, and MG afferents produced larger EPSPs in caudal than in rostral MG motoneurons. These spatial effects were in accord with the more rostral entry of LG than MG Ia afferents into the spinal cord. The differential projection of SOL afferents to MG and SOL motoneurons which overlap spatially in the spinal cord suggests a species specificity in addition to a location specificity.

Animals↗

The effect of peripheral nerve cross-union on connections of single Ia fibers to motoneurons.

The distribution of Ia terminals to alpha-motoneurons has been investigated under conditions where a) the Ia fiber innervates a foreign muscle and b) the motor axon innervates a foreign muscle. This distribution has been assessed by examining which motoneurons develop an EPSP in response to stimulation of a single Ia afferent fiber. Cross-union of the medial gastrocnemius and lateral gastrocnemius-soleus nerves has been performed in 5--8 day old kittens and the effect of this procedure on Ia connections to alpha-motoneurons has been investigated in the adult about one year later. No rearrangement of synaptic connections has been observed under these conditions. The connections from self-unioned Ia afferents and to self-unioned motoneurons are also normal. The individual EPSP's in these motoneurons with regenerated axons have normal rise times. The findings of normal Ia connections as well as normal EPSP rise times in alpha-motoneurons with regenerated motor axons indicates reversibility of the changes seen in axotomized motoneurons.

Animals↗

Terminals of single Ia fibers: distribution within a pool of 300 homonymous motor neurons.

The excitatory postsynaptic potentials produced in motoneurons by impulses in single afferent fibers (Ia) have been recorded with the aid of an averaging computer. These responses were used to map the distribution of the terminals of single fibers within the pool of 300 motoneurons of the medial gastrocnemius muscle. Twelve Ia fibers were studied in separate experiments. Monosynaptic excitatory postsynaptic potentials were found in 94 percent of the 77 motoneurons investigated. This finding indicates that each of the 300 motoneurons must receive afferent fibers from almost all of the spindles of the muscle it innervates.

Animals↗

Neurotrophins, nociceptors, and pain.

It is now well established that neurotrophins play a crucial role in the development of the nervous system. However, there is increasing evidence that the function of neurotrophins persists throughout adulthood. The broad scope of neurotrophin action is well documented in the case of nerve growth factor (NGF) and its effect on nociceptors and nociception. Here, we review the evidence for these multiple roles for NGF. Two manipulations influencing NGF levels are discussed in detail. The first involves the use of transgenic mice that overexpress or underexpress neurotrophins. A second strategy involves administration of NGF or its antibody in vivo to increase or decrease its level. During prenatal development, NGF is required for survival of nociceptors. In the early postnatal period, NGF is required for expression of the appropriate nociceptor phenotype. In adults, NGF acts as an important intermediate in inflammatory pain, contributing to both peripheral and central sensitization. The sensitization of peripheral nociceptors can be very rapid and can involve non-neural cells such as mast cells, neutrophils, fibroblasts, and macrophages. Recent evidence indicates that other neurotrophins also play key supporting roles in the development of nociceptors (e.g., NT-3) and in inflammatory pain (e.g., BDNF, NT-4/5). Furthermore, molecules from other superfamilies (e.g., GDNF) also are required to assure survival of certain classes of nociceptors. The diverse effects of neurotrophins on nociceptive processing emphasize their broad importance in the development and function of the nervous system.

Animals↗

Retrograde effects on synaptic transmission at the Ia/motoneuron connection.

The fidelity of impulse propagation through the complex axonal tree en route to the various target cells of that fiber is an important question in neurobiology. Anatomists can trace pathways, but if impulses fail to propagate down to the terminals to release transmitter onto the target cell, there is a significant 'disconnect' between anatomy and physiology. These issues have been studied at length in the spinal cord of the cat where it has proven possible to examine the connections made by afferent fibers on motoneurons under different stimulus conditions. EPSP amplitude varies systematically during high frequency stimulation of the afferents according to the identity of the target motoneuron. This variation is a function of the state of the motoneuron's relation to its peripheral target. It changes after motoneuron axotomy and recovers with reinnervation of the periphery. Neurotrophins delivered to the axotomized motor axons fail to induce recovery. Chronic stimulation of the motor nerve alters muscle properties with coordinated changes in properties of the synapses on motoneurons innervating the stimulated muscle. We cannot yet definitively establish the mechanisms determining synaptic behavior during high frequency stimulation. However, the retrograde regulation of these properties suggests that it is an important variable and thus is worthy of intensive further study.

Animals↗