Motor versus sensory neuron regeneration through collagen tubules.

Differences in regeneration of sensory and motor nerves were studied in rats to determine the effects of entubulation with collagen conduits. The rat sciatic nerve was repaired either with a 10-mm saline-filled gap or with a no-gap end-to-end repair cuffed within collagen tubules. These repairs were compared with the standard epineurial repairs. The populations of regenerated motor and sensory neurons in the peroneal nerves of all repairs were compared against the populations of normal peroneal neurons using horseradish peroxidase retrograde labeling. The epineurial repair resulted in regeneration of 65 percent (409 +/- 150) of motor neurons and 79 percent (2127 +/- 516) of sensory neurons (n = 6). The no-gap end-to-end repair in a collagen tubule resulted in regeneration of 53 percent (338 +/- 203) of motor and 70 percent (1893 +/- 794) of sensory neurons (n = 7). In the 10-mm gap repair, only 6.2 percent (39 +/- 18) of motor neurons but 63 percent (1710 +/- 557) of sensory neurons regenerated (n = 5). These results show that collagen entubulation supports nerve regeneration in end-to-end nerve repairs comparably to standard epineurial suture repairs. With the 10-mm gap repairs in collagen tubules, sensory neurons regenerated consistently better than motor neurons in the same environment. Therefore, intrinsic differences exist between motor and sensory neuron regeneration in the same nerve.

Most dorsal root ganglion neurons of the adult rat survive nerve crush injury.

Severe crush of the rat sciatic nerve does not result in any significant cell death among motor neurons (Swett et al., 1991a). The present study reports on the survival of the dorsal root ganglion (DRG) neurons in the same experiments. From 15 to 187 days after crush of the left sciatic nerve, the common peroneal or sural nerve was cut and labeled distal to the injury with a mixture of horseradish peroxidase (HRP) and its wheatgerm agglutinin conjugate (WGA:HRP). In other cases, the crush injury was made far enough distally on a peroneal or sural branch to permit labeling several millimeters proximal to the injury. The procedures for reconstructing the regenerated DRG neuron populations were identical to those used in an earlier study describing the normal sciatic DRG neuron populations in the rat (Swett et al., 1991b). The normal peroneal nerve contains 2699 +/- 557 DRG neurons. When the peroneal nerve was crushed near its point of origin from the sciatic and labeled 10 mm distal to the injury, 2186 +/- 163 DRG neurons were counted, suggesting a decrease of about 19% (p < 0.01). However, when the entire sciatic nerve was crushed, distal labeling of the peroneal nerve revealed a mean number of 2578 +/- 291 DRG neurons, an insignificant reduction (p > 0.2). When the peroneal nerve was labeled proximal to a peroneal crush site, a similar number of DRG neurons (2563 +/- 412) was counted. Results following sural nerve crush were similar. The sural nerve normally contains 1675 +/- 316 DRG neurons. When the nerve was labeled distal to the injury, 1558 +/- 64 DRG neurons were counted--a number almost identical to that found (1529 +/- 240) when this nerve was labeled proximal to the injury. The results demonstrate that within 6 months of severe crush injury of the rat sciatic nerve, the vast majority of DRG neurons survive and regenerate new axons distally beyond the injury site, presumably to reinnervate their original targets.

Sensory neurons of the rat sciatic nerve.

Experiments have been undertaken in this laboratory over recent years to accurately determine the numbers and sizes of somatic neurons which contribute to the normal sciatic nerve, at mid-thigh levels, of the adult, albino rat. This article is concerned with the dorsal root ganglion (DRG) neuron population of the sciatic nerve whose cell bodies were identified through retrograde labeling of cut branches of the sciatic with horseradish peroxidase (HRP) and/or its wheat germ conjugate (WGA-HRP). It is essential to understand the neuronal composition of the normal rat sciatic nerve if the consequences of aging, nerve injury, and surgical repair to improve functional regeneration are to be properly evaluated. Neuron counts were determined from camera-lucida paper drawings of all labeled profiles in DRGs L3-L6 at 100 x magnification. The profiles, obtained by labeling individual branches of the sciatic nerve (sural, lateral sural, tibial, peroneal, medial, and lateral gastrocnemius/soleus nerves) were traced from 40-microns-thick, serial, frozen sections. The sizes of the perikarya, areas and diameters, were determined by tracing the perimeters of the drawn profiles on a digitizing tablet. The tablet's output was inputted directly into a specially designed computer spreadsheet which contained a mathematical table for correcting the split-cell error inherent to the sectioning process. Afferents from any given branch of the sciatic normally occupied two to three adjacent ganglia. Sciatic DRG neurons were normally located in lumbar ganglia L3-L6. Nearly 98-99% of all sciatic DRG perikarya resided in the L4 and L5 DRGs. The L6 DRG, traditionally regarded as an important contributor to the rat sciatic, contained merely 0.4% of its afferent neurons while the L3 ganglion, frequently overlooked as a contributor, contained 1.2% of the mid-thigh sciatic afferents. The mean size of rat DRG neurons was about 29 microns (550-600 microns2). The corrected counts revealed that the normal sciatic nerve (at mid-thigh levels), in rats between 2 and 12 months of age, contained a mean, total DRG neuron population of about 10,500 neurons. This is probably an underestimate by 3-5% of the true number due to occasional unreliable labeling of some of the small DRG neurons. It is estimated that the normal, mean number of sciatic DRG neurons of young to middle-aged rats lies somewhere between 10,500 and 11,000 +/- 2000. The data suggest that nearly 20% of all DRG neurons in the sciatic nerve supply muscle afferents. The vast majority of the remaining neurons are involved with innervation of the skin.(ABSTRACT TRUNCATED AT 400 WORDS)

All peroneal motoneurons of the rat survive crush injury but some fail to reinnervate their original targets.

This is a quantitative study of the motoneuronal population of the rat's common peroneal nerve following severe crush injury of the sciatic nerve or its component branches. The crush was performed unilaterally under anesthesia for 60 seconds with hemostat jaws covered with tubing to form a smooth, 2 mm long, injured zone. Recovery from injury was allowed for 14 to 188 days. It was measured behaviorally using the sciatic functional index (SFI) and electrophysiologically by comparing the conduction velocity and amplitudes of evoked muscle action potentials prior to injury, and again after injury just before the nerve was labeled with horseradish peroxidase (HRP), and/or its wheat germ agglutinin conjugate (WGA-HRP), 48-72 hours before sacrifice. The motoneurons were retrogradely labeled on both sides so that the uninjured side might serve as a control. On the injured side the nerves were labeled either distal or proximal to the crush site. The tibialis anterior muscles on both sides were removed and weighted. Spinal segments L2 to L6 were cut in serial, frozen cross-sections. HRP reaction products were formed using TMB as the chromogen. The normal peroneal nerve was found to contain 634 +/- 26 motoneurons (22 cases). The number of motoneurons labeled 5-15 mm distal to the injury site (22 cases) was 535 +/- 69 or 84.4% of normal. In 12 cases in which the nerve was labeled 5 mm proximal to the injury normal population numbers (648 +/- 30) were found. These counts demonstrated that the unlabeled 15.6% in the distal labeled cases had not vanished as a result of cell death. Instead, the unlabeled group was composed mainly of small motoneurons whose axons probably had not regenerated distal to the crushed zone. Mean soma size of injured neurons increased to maximum 3-6 weeks after injury and then gradually decreased in size over the following weeks to nearly normal values. This transient increase in size was due to two factors: 1) soma swelling in response to axonal injury, and 2) absence of many small motoneurons, presumably gamma-motoneurons, which were either incapable of, or prevented from, regenerating beyond the injury zone long after larger motoneurons had reinnervated their targets. SFI scores, muscle weights, and amplitude ratios of evoked potentials recovered to control values by 70-80 days post-injury. Conduction velocities remained 20-25% below normal at the end of 80 days.(ABSTRACT TRUNCATED AT 400 WORDS)

Repair of severed peripheral nerve: a superior anatomic and functional recovery with a new "reconnection" technique.

The objective of this study was to use a quantitative functional and anatomic model to compare surgical repair of the rat sciatic nerve according to two techniques; standard epineurial repair and the recently reported "nerve reconnection technique" ("freeze-trim technique"). Functional recovery was evaluated using a functional index based on the measurements of the rats' footprints. Neuroanatomic experiments were conducted on the same animals to correlate functional recovery with regeneration of known motoneuron populations. The results of surgical repairs were also compared to those obtained from untreated sciatic nerve crush injuries. Functional recovery after epineurial repairs typically averaged 18%, whereas the mean recovery from the "nerve reconnection technique" was 71%. Crush injuries recovered to normal and reached a plateau much earlier than the surgical repairs. Retrograde horseradish peroxidase (HRP) labeling of motoneurons of the common peroneal nerve, a branch of the sciatic, revealed that there was a complex relationship between functional recovery and the number and distribution of motoneurons that regenerated axons distal to the repair site. The "nerve reconnection technique" greatly reduced the probability of axonal misdirection into the wrong distal branches at the repair site and brought an improvement of 300% to 400% in functional recovery over that found with epineurial repair. This technique of nerve repair may prove to be a valuable tool in reconstructive surgery.

Motoneurons of the rat sciatic nerve.

The sciatic nerve of the rat is a commonly used model for studies on nerve injury, regeneration, and recovery of function. To interpret the changes that occur in a neuron population subsequent to peripheral nerve injury, and to compare different repair procedures, it is essential to have a complete and accurate understanding of the population's normal cellular constituents and their locations. This study reports on the numbers, sizes, and topographic distributions of the motoneuron populations of individual branches of the rat sciatic nerve (peroneal, tibial, sural, and the medial and lateral gastrocnemius nerves), as determined by retrograde transport of HRP (or WGA-HRP) from cut proximal nerve ends isolated in wax to prevent spread of the tracer substance. Optimal labeling of motoneurons was evident between 42 and 73 h of survival. Reconstructions were made from 40-micron serial sections of spinal segments L6 through L2, usually in the coronal plane. Accurate motoneuron counts were obtained by detailed reconstructions in which an accounting of all "split cell" fragments was made to avoid double cell counts. The sciatic nerve of the albino rat contains a total population of about 2005 +/- 89 motoneurons. The tibial nerve contained 982 +/- 36 cells or 49% of the total. The common peroneal nerve contained 31% or 632 +/- 27 motoneurons. The medial and lateral gastrocnemius nerve branches contained collectively 322 +/- 16 (16%). The sural nerve accounted for only 68 +/- 10 motoneurons (3%). The sciatic motoneurons form a continuous, compact cell column in the dorsolateral quadrant of the ventral horn extending from rostral L6 into the caudal third of L3 over a longitudinal distance of about 6.3 to 7.5 mm. This fusiform column shows its greatest width, 0.5 mm, in mid-L4. Within this compartment motoneurons of each branch of the sciatic occupy spatially distinct subcompartments. Their relative positions are described in detail.

The pattern of spinal and medullary projections from a cutaneous nerve and a muscle nerve of the forelimb of the cat: a study using the transganglionic transport of HRP.

The transport of HRP into the spinal cord and medulla in the cat has been examined from a forelimb cutaneous nerve, the lateral superficial radial nerve (LSR), and from the muscle nerves supplying both heads of the forelimb muscle, extensor carpi radialis (ECR). HRP transported by the LSR was widely distributed in the spinal cord throughout laminae I-IV in the vicinity of the root entry zone and from spinal segments T1 to C5. HRP was also transported from the LSR to the medulla where there was intense patchy, discontinuous labelling in the main cuneate nucleus. The pattern of labelling in the cuneate nucleus did not follow any simple somatotopic plan. Exposure of the muscle nerve to HRP led to labelling in the spinal dorsal horn in lamina I, in the deep dorsal horn on the lamina V/VI border, and in lateral and medial lamina VI at sites that contain cells of origin of spinocerebellar tracts. The medial lamina VI label was contiguous with a deposit that extended medially to the central canal. The label in lateral lamina VI was patchy and formed a discontinuous column from T1 to C5. HRP transported by the muscle nerve also produced label in the more ventral regions of the cuneate nucleus where it had a lacy appearance, in part due to its extensive distribution around dendrites. A relatively dense, patchy, and discontinuous deposit of reaction product was also present in the external cuneate nucleus after muscle nerve exposure. This deposit was most intense on the dorsomedial surface of this nucleus, but another, less intense, deposit was also present ventrally.

Long ascending projections to the midbrain from cells of lamina I and nucleus of the dorsolateral funiculus of the rat spinal cord.

Small volumes (5-40 nl) of an aqueous solution of wheat-germ-agglutinin-conjugated horseradish peroxidase (WGA-HRP) were injected unilaterally into midbrain structures of 18 adult, albino rats. In 17 of these preparations cells of many types were found to be retrogradely labeled in cervical and lumbar spinal cord segments. The data reported here concern the number and location of labeled cells from injection sites in the midbrain that affected two distinct cell populations: neurons within the marginal layer (lamina I cells) and neurons of the nucleus of the dorsolateral funiculus (NDLF cells). In ten of the preparations, only nine of which are reported in detail here, a total of 1,831 labeled lamina I cells were identified. In the lumbar enlargement they reached a density of more than 60 cells/mm. Of these, 85% projected to medial portions of the caudal, contralateral midbrain. Injection sites that were centered in the caudal periaqueductal gray (PAG) and/or in the immediately adjacent region of nucleus cuneiformis labeled the largest numbers of lamina I cells. Cells of the NDLF were retrogradely labeled in all preparations in which lamina I cells were labeled but they were also observed in five cases in which lamina I cells were not labeled. A total of 1,914 NDLF cells were labeled from all injection sites. These cells were found to have essentially a bilateral distribution with 57% of the cells located in the contralateral DLF. Although there is substantial overlap between the terminal fields of lamina I and NDLF cells within the midbrain, NDLF cells had a more diffuse target area encompassing the reticular core of the midbrain and PAG, bilaterally, while the target area for lamina I cells was comparatively discrete, being largely restricted to the more medially situated midbrain structures, contralaterally. Whether the terminations of lamina I cells in and near the PAG are from collaterals of spinothalamic neurons originating in lamina I, or a subclass of lamina I neurons that project exclusively to the midbrain, is not known. It is significant, however, that lamina I cells, known to be activated by noxious stimuli to the skin, should project to a region of the brain stem from which analgesia can be produced by electrical stimulation or by local application of opiates.

Distribution of dipeptidyl peptidase II (Dpp II) in rat spinal cord.

The histochemical localization of dipeptidyl peptidase II (Dpp II; E.C. 3.4.14.2) activity was demonstrated at the light microscope level in the rat spinal cord. Prominent staining was observed in motoneurons of the ventral horn and in medium to large neurons in the deep laminae of the dorsal horn, the intermediate gray, and in lamina X surrounding the spinal canal. Within neurons, Dpp II was localized largely in cell perikarya and large primary dendrites with no staining observed in cell nuclei. Neurons in the superficial dorsal horn lack Dpp II enzyme activity. Nonneuronal elements which also stained prominently were pericytes associated with blood vessels and ependymal cells lining the lumen of the spinal canal. A few oligodendrocytes and astrocytes were also stained, but they represented a minor component of the total amount of Dpp II activity. Following ventral root injury, Dpp-II-containing motoneurons degenerate; some glial cells in the region of degenerating neurons become Dpp II positive. The localized distribution of Dpp II in spinal cord neurons suggests that this proteolytic enzyme may play a role in the metabolism of an unidentified neuropeptide.

The somatotopic organization of primary afferent terminals in the superficial laminae of the dorsal horn of the rat spinal cord.

Transganglionic transport of wheatgerm agglutinin conjugated horse-radish peroxidase (WGA-HRP) was used to reveal the central distribution of terminals of primary afferent fibers from peripheral nerves innervating the hind leg of the rat. In separate experiments the sizes and locations of cutaneous peripheral receptive fields were determined by electrophysiological recording techniques for each of the nerves that had been labeled with WGA-HRP. By using digital image analysis, the sizes and positions of the peripheral receptive fields were correlated with the areas of superficial dorsal horn occupied by terminals of primary afferents from each of these receptive fields. Data were obtained from the posterior cutaneous nerve of the thigh, lateral sural, sural, saphenous, superficial peroneal, and tibial nerves. The subdivisions of the sciatic nerve, the sural, lateral sural, superficial peroneal, and tibial nerves each projected to a separate and distinct region of the superficial dorsal horn and collectively formed a "U"-shaped zone of terminal labeling extending from lumbar spinal segments L2 to the caudal portions of L5. The gap in the "U" extended from L2 to the L3-4 boundary and was occupied by terminals from the saphenous nerve. Collectively, all primary afferents supplying the hindlimb occupied the medial 3/4 of the superficial dorsal horn with terminals from the tibial nerve lying most medially and occupying the largest of all the terminal fields. Afferents from the superficial peroneal lay in a zone between the medially situated tibial zone and the more laterally placed sural zone. Afferents from the posterior cutaneous nerve were located most caudally and laterally. Terminal fields from the posterior cutaneous and saphenous nerves differed from the others in having split representations caused presumably by their proximity to the mid-axial line of the limb. Comparisons between the peripheral and the central representations of each nerve revealed that 1 mm2 of surface area of the superficial dorsal horn serves approximately 600-900 mm2 of hairy skin and roughly 300 mm2 of glabrous skin. The vast majority of terminal labeling observed in the dorsal horn was found in the marginal layer and substantia gelatinosa, suggesting that small diameter afferents have an orderly somatotopic arrangement in which each portion of the skin surface is innervated by afferent fibers that terminate in preferred localities within the dorsal horn.

The cutaneous contribution to the hamstring flexor reflex in the rat: an electrophysiological and anatomical study.

The location and properties of the cutaneous receptive fields responsible for detecting the flexor withdrawal reflex in the posterior head of biceps femoris (pBF) and semitendinosus (ST) components of the hamstring muscle have been examined in unanaesthetized decerebrate rats, spinalized at T10-T11. Single alpha-motoneurone efferents were recorded from the nerve to pBF and the principal head of ST and their responses to ipsi- and contralateral hindlimb skin stimulation investigated. The efferents to both muscles characteristically had a low or absent background discharge and they all had mechanoreceptive fields on the ipsilateral foot. The mechanical threshold of these fields was high with no response to light touch or brush. Fifty-four percent of these units also had a smaller and weaker contralateral mechanoreceptive field. The only apparent difference between ST and pBF efferents was that more ST efferents had contralateral fields than pBF units. Noxious, hot and cold thermal stimuli applied to the ipsilateral foot activated 56% of the efferents. Mustard oil, a chemical irritant, produced a long-lasting flexor response when applied to the ipsilateral foot. The responses of these efferents to stimulation of A beta, A delta and C cutaneous afferents in the sural nerve were also studied. Short latency reflexes were elicited in all efferents by A beta inputs, longer latency reflexes were elicited in 64% by A delta inputs and very long latency responses with long afterdischarges were found in 73% of the units to C inputs. Retrograde labelling of the hamstring motoneurones with WGA-HRP indicated that they lay in ventrolateral lamina IX extending from the caudal portion of the third lumbar segment to the junction of the 5th and 6th lumbar segments. Transganglionic labelling of small diameter primary afferent terminals in the dorsal horn of cutaneous nerves innervating the foot revealed that the longitudinal distribution corresponded closely with that of the hamstring motor nucleus. The flex-or reflex in the spinal rat provides a useful model therefore, for studying how the input in nociceptive afferents is processed and transformed within the spinal cord, to produce appropriate outputs.

Behavioral detection of subcortical stimuli: comparison of somatosensory and "motor" circuits.

Cats were trained to press a lever for food reinforcement in response to stimulation of the ventral lateral (VL) nucleus of the thalamus and the deep cerebellar nuclei. By scaling stimulus intensities relative to the appearance of a minimal amplitude evoked response in pericruciate cortex, it was possible to measure behavioral detection thresholds and correlate behavior with electrocortical activity. With stimulus rates of 25 Hz or greater, VL was the least effective stimulus site for producing detection. At stimulus rates less than 25 Hz, stimulation of the lateral or interpositus nuclei was even less effective in eliciting behavior, but at rates of 25 Hz or more, detection thresholds decreased below those for VL stimulation; cerebellar stimulation produced detection as readily as had stimulation of the ventrobasal complex in other experiments. These findings suggest that the cerebellum may modulate sensory experiences and that some portions of cerebral cortex, the pericruciate and suprasylvian regions, do not appear to be directly involved in mediating sensory detection. It is postulated that the neural detection circuits are more likely to be found in subcortical than in cerebrocortical structures.

Effect of sensorimotor cortical ablation on the placing reaction in the standing cat.

The placing reaction in the standing cat permits the analysis of a movement, the placing movement, together with its postural support. It is provoked by one of two moving plates coming into contact with one forelimb. Each limb rests on a platform equipped with strain gauges which permit changes in force exerted by each limb to be recorded. The placing reaction is characterized by two phases, an early isometric phase lasting until the lift-off of the stimulated limb occurs. It is then that a diagonal postural support on one forelimb and the opposite hindlimb takes place so that the placing movement can take place. Performance of this movement corresponds to the second phase. Four cats underwent an unilateral lesion in sensorimotor cortex. Two animals had a large lesion extending to the pre- and post-cruciate regions and from the midline to the coronal sulcus, including a large part within the depth of that sulcus. Two other cats had a restricted lesion covering mainly the forelimb part of area 4. After extensive cortical lesions, permanent changes in the contralateral placing reaction were observed. The isometric phase increased in duration, without marked changes of the pattern of postural support whereas the movement was prolonged and usually hypermetric. On the contrary, ipsilateral placing with its associated postural support was unmodified. After restricted cortical lesions, only temporary changes were observed. Recuperation was complete within 30 postoperative days. It was concluded that motor cortex on one side controls, as a whole, the contralateral placing movement and its associated postural adjustment, whereas it does not significantly modify the ipsilateral placing and its associated postural responses notwithstanding the use of the contralateral limbs in this adjustment.

Detection thresholds to stimulation of ventrobasal complex in cats.

Cats were trained to indicate, by bar pressing for food rewards, their detection of stimulation of the ventrobasal (VB) complex delivered through implanted bipolar electrodes. By varying stimulus intensity it was possible to determine thresholds for detection. Scaling stimulus intensity relative to the appearance of a minimal evoked potential allowed comparisons between animals and also comparisons with results obtained by stimulation of peripheral nerve. Animals could detect VB stimulation, but only at stimulus intensities consistently stronger than those required for minimal appearance of an evoked response in ipsilateral primary somatosensory cortex. Results of VB activation differed from cutaneous nerve effects in that VB detection thresholds were markedly influenced by stimulus frequency. They were lowest at frequencies above 30 Hz and increased greatly at lower frequencies. Discomfort or pain did not seem to result even from relatively high stimulus intensities. The results compare well with observations obtained from stimulation of VB in humans. The appearance of an evoked cortical response is not necessarily correlated with behavior. Under appropriate conditions, behavior can be elicited predictably with minimal electrocortical activity; under other conditions detection may be absent even when large numbers of cortical neurons are activated. We suggest that regions of the cerebral cortex receiving thalamocortical projections from VB may not be essential in the detection process.

The placing reaction in the standing cat: a model for the study of posture and movement.

By measuring the forces applied by each limb supporting the weight of the standing quadruped (cat), before and during elicitation of the placing reaction, it was possible to examine quantitatively and qualitatively the postural events which preceded and accompanied forelimb displacement. The findings are summarized as follows: 1. Postural adjustment consists of a shift from quadrupedal stance to a tripodal stance to permit withdrawal of weight from one forelimb without loss of equilibrium. The animal's weight is not equally distributed between the three supporting limbs but the majority of the weight is supported by the diagonally opposing limb pair. 2. During the isometric phase of the placing reaction, the animal's projected center of gravity moves contralaterally, across the diagonal line between the contralateral forepaw and the ipsilateral hindpaw, and comes to rest within the triangular zone outlined by the three supporting limbs. 3. The diagonal supporting stance is a maneuver of an anticipatory nature which precedes and accompanies the placing reaction. 4. The force changes exhibited by each limb to bring the animal to the stereotyped diagonal supporting stance illustrated that the way to achieve this is consistent within a given animal, but differs from one animal to another. The pattern in the same animal is generally symmetrical when lifting the right or left forepaw. 5. The data from the cat are compared to observations in other quadrupeds and man.

A device used for study of postural reactions in the quadruped.

A device used for study of postural reactions associated with placing movement in the quadruped is described. The apparatus consists of three basic components; a set of 4 strain gauge platforms on which the quadruped is trained to stand, a restraining device to keep the animal positioned over the strain gauge platforms and two mobile plates which mechanically stimulate the left or the right forelimb to produce the placing movement. The contact placing reaction consists of an early phase of preparatory positioning of the body (a postural adjustment) and a later phase of limb displacement, superimposed on a postural stance, during which the animal lifts its forepaw from the ground and then replaces it on top of one of the mobile plates.

Mechanical transduction in the Golgi tendon organ: a hypothesis.

Morphological evidence, gained from light and electron microscopy, has shown that the unmyelinated terminal branches of the Ib afferent fiber innervating the Golgi tendon organ (GTO) lie within the spaces between braids of collagen. Based on empirical data it is proposed that force applied to a muscle's tendon will straighten these collagen braids and cause compressional deformation of the axon branches trapped between them. The mechanical events, which are presumed to occur within the GTO, appear to explain how it may function as a biological force transducer under static loading conditions. The mechanical principal described for the GTO may be a primitive and wide-spread biological mechanism employed by certain types of sensory receptors that function as position (and force) detectors.