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PubMed2004

Polscope analysis of meiotic spindle changes in living metaphase II human oocytes during the freezing and thawing procedures.

BACKGROUND: The clinical efficacy of the current methods used for cryopreservation of metaphase II human oocytes is low. Meiotic spindle disorders are thought to be largely responsible for this situation. METHODS: Supernumerary fresh metaphase II human oocytes were cryopreserved in 1,2-propanediol with 0.1 M sucrose using a slow freezing/rapid thawing programme. Meiotic spindles were analysed in these living metaphase II oocytes at sequential steps of the freezing and thawing procedures with the use of a computer-assisted polarization microscopy system (Polscope). RESULTS: The meiotic spindle was detected in all 56 oocytes (from 16 patients) before freezing and remained visible in all these oocytes throughout the preparation for freezing up to the time that they were loaded into cryopreservation straws. Immediately after thawing, the spindle was visible in 35.7% of oocytes, but it disappeared in all of the thawed oocytes during the subsequent washing steps. However, the spindle reappeared in all surviving thawed oocytes after washing (57.4%), by 3 h of incubation at 37 degrees C in culture medium. CONCLUSIONS: The current techniques of oocyte freezing and thawing inevitably cause meiotic spindle destruction. All spindles observed in thawed oocytes result from post-thaw reconstruction.

Cell Survival↗

PubMed1995

Chloral hydrate induced spindle aberrations, metaphase I arrest and aneuploidy in mouse oocytes.

In view of tissue- and sex-specific differences in chemically-induced aneuploidy, we analysed the effects of chloral hydrate (CH) on cell-cycle progression, spindle formation and aneuploidy in in vitro maturing mouse oocytes with cytogenetic and immunofluorescent methods. CH blocks oocyte maturation irreversibly and concentration dependently. During culture in 125 micrograms/ml CH, germinal vesicle breakdown is delayed, and most oocytes become arrested in meiosis I with bivalent chromosomes. Their spindles are asymmetric or attain fusiform poles. Oocytes which progress to metaphase II also possess astral instead of barrel-shaped, anastral spindles as characteristic for the controls. Resolution of chiasmata without polar body extrusion during exposure to 50 and 125 micrograms/ml CH results in significant rises in 'diploid' metaphase II oocytes. Hyperploidy rates do not increase significantly at any concentration of CH, but hypoploidy levels are elevated at 125 micrograms/ml CH. CH induces lagging of chromosomes during telophase I, inhibits spindle elongation in anaphase B and causes chromosome displacement from the spindle equator in metaphase I and II. Oocytes also become irreversibly arrested in maturation when exposed to CH prior to resumption of maturation, or when CH is present during the first or second 8 h of maturation. Therefore, these data show unequivocally that CH is a potent aneugen in female germ cells, affecting spindle shape, cytokinesis and cell-cycle progression. However, a metaphase I checkpoint in mammalian oogenesis sensing disturbances in the spindle appears to prevent nondisjunction efficiently in most oocytes. In this in vitro model the aneugenic activity of drugs, critical periods in oocyte maturation, threshold concentrations, and targets of drug action can be directly assessed.

1-Methyl-3-isobutylxanthine↗

PubMed2003

Rotation of meiotic spindle is controlled by microfilaments in mouse oocytes.

The completion of meiosis requires the spatial and temporal coordination of cytokinesis and karyokinesis. During meiotic maturation, many events, such as formation, location, and rotation of the meiotic spindle as well as chromosomal movement, polar body extrusion, and pronuclear migration, are dependent on regulation of the cytoskeleton system. To study functions of microfilaments in meiosis, we induced metaphase II (MII) mouse oocytes to resume meiosis by in vitro fertilization or parthenogenetic activation, and we treated such oocytes with cytochalasin B (CB). The changes of the meiotic spindle, as visualized in preparations stained for beta-tubulin and chromatin, were observed by fluorescent confocal microscopy. The meiotic spindle of MII oocytes was observed to be parallel to the plasmalemma. After meiosis had resumed, the spindle rotated to the vertical position so that the second polar body could be extruded into the perivitelline space. When meiosis resumed and oocytes were treated with 10 micro g/ml of CB, the spindle rotation was inhibited. Consequently, the oocyte formed an extra pronucleus instead of extruding a second polar body. These results indicate that spindle rotation is essential for polar body extrusion; it is the microfilaments that play a crucial role in regulating rotation of the meiotic spindle.

Actin Cytoskeleton↗

PubMed1996

Expression of Bcl-xL and loss of p53 can cooperate to overcome a cell cycle checkpoint induced by mitotic spindle damage.

During somatic cell division, faithful chromosomal segregation must follow DNA replication to prevent aneuploidy or polyploidy. Damage to the mitotic spindle is one potential mechanism that interferes with chromosomal segregation. The accumulation of aneuploid or polyploid cells resulting from a disrupted mitotic spindle is presumably prevented by cell cycle checkpoint controls. In the course of studying cells that overexpress the apoptosis-inhibiting protein Bcl-xL, we found that these cells have an increased rate of spontaneous tetraploidization, suggesting that apoptosis may play an important role in eliminating cells that fail to complete mitosis properly. When cells expressing Bcl-xL are treated with mitotic spindle inhibitors, a significant percentage reinitiate DNA replication and become polyploid. Nevertheless, the majority of cells expressing Bcl-xL undergo a prolonged p53-dependent cell cycle arrest following mitotic spindle damage. Unexpectedly, p53 expression is not induced in mitosis, nor does it influence M-phase arrest. Instead, cells with mitotic spindle damage only transiently arrest in M phase, and despite failing to complete mitosis, appear to proceed to G1. During this subsequent growth factor-dependent phase, p53 is induced and mediates cell cycle arrest. In cells that do not overexpress Bcl-xL, elimination of the p53-dependent growth arrest with a dominant negative mutant also results in polyploidy after mitotic spindle damage, but under these conditions most cells die by apoptosis. Expression of Bcl-xL and abrogation of p53 cooperate to allow rapid and progressive polyploidization following mitotic spindle damage. Our results suggest that suppression of apoptosis by bcl-2-related genes and loss of p53 function can act cooperatively to contribute to genetic instability.

Apoptosis↗

PubMed2004

Spindle checkpoint regulates Cdc20p stability in Saccharomyces cerevisiae.

The spindle checkpoint arrests cells at the metaphase-to-anaphase transition until all chromosomes have properly attached to the mitotic spindle. Checkpoint proteins Mad2p and Mad3p/BubR1p bind and inhibit Cdc20p, an activator for the anaphase-promoting complex (APC). We find that upon spindle checkpoint activation by microtubule inhibitors benomyl or nocodazole, wild-type Saccharomyces cerevisiae contains less Cdc20p than spindle checkpoint mutants do, whereas their CDC20 mRNA levels are similar. The difference in Cdc20p levels correlates with their difference in the half-lives of Cdc20p, indicating that the spindle checkpoint destabilizes Cdc20p. This process requires the association between Cdc20p and Mad2p, and functional APC, but is independent of the known destruction boxes in Cdc20p and the other APC activator Cdh1p. Importantly, destabilization of Cdc20p is important for the spindle checkpoint, because a modest overexpression of Cdc20p causes benomyl sensitivity and premature Pds1p degradation in cells treated with nocodazole. Our study suggests that the spindle checkpoint reduces Cdc20p to below a certain threshold level to ensure a complete inhibition of Cdc20p before anaphase.

Anaphase↗

PubMed2004

Coexistence of spindle cell lipoma and ordinary lipoma.

We report a patient with a spindle cell lipoma on the nape and three ordinary lipomas on the abdomen and extremities. The coexistence of spindle cell lipoma and ordinary lipoma in a single patient is rare. Abundant CD34-positive spindle cells and mast cells were found in the spindle cell lipoma, but in the ordinary lipomas, only a small number of CD34-positive spindle cells were found in the interstitial connective tissue and no mast cells were seen. Because mast cells are known to stimulate mesenchymal cell proliferation and collagen production, mast cell infiltration may be a trigger for the proliferation of CD34-positive spindle cells, leading to the conversion of ordinary lipoma into spindle cell lipoma.

Antigens, CD34↗

PubMed2006

Schizosaccharomyces pombe homolog of Survivin, Bir1p, exhibits a novel dynamic behavior at the spindle mid-zone.

Members of the BIR-domain containing Survivin family of proteins have been identified in a variety of eukaryotes and are known to play important roles in the regulation of mitosis. The Schizosaccharomyces pombe homolog of Survivin, Bir1p, is essential for chromosome condensation and spindle elongation and integrity. Bir1p, a nuclear protein, resides at the kinetochores in metaphase and anaphase A and spreads to the spindle mid-zone in anaphase B. Here we show that this relocation requires Cdk (Cyclin dependent kinase) inactivation and intact microtubules. With the aid of a kinesin mutant, klp5Delta, we also show that completion of anaphase A is vital for effecting Bir1p re-location to the spindle mid-zone. Although minimal exchange of Bir1p sub-units occurs between the spindle and the nucleoplasm, the protein redistributes laterally within the mid-zone region. Bir1p dynamics therefore significantly differs from that of tubulin on an anaphase B spindle, which is loaded at the plus ends of growing microtubules and shows no lateral redistribution within the spindle. Thus, Bir1p, and possibly its associated proteins, might organize a dynamic mid-zone region that helps spindle elongation and maintenance.

Anaphase↗

PubMed1968

Thresholds of cortical activation of muslce spindles and alpha motoneurones of the baboon's hand.

1. Much current thinking about voluntary movement assumes that the segmental gamma loops can function as a servomechanism operated by the brain. However, the alpha motoneurones of the baboon's hand receive a powerful monosynaptic (CM) projection from the precentral gyrus. If servo-driving from the same cortical area is to be possible, it must project independently to the fusimotor neurones and have sufficient power to increase the afferent signalling from the muscle spindles. The cortical thresholds for contraction of m. extensor digitorum communis and for acceleration of the discharges of its muscle spindles have therefore been compared.2. Significant results in this context require that the spindles studied be coupled in parallel with the responding extrafusal muscle fibres. Many spindles were not unloaded by the submaximal contractions evoked by cortical stimulation, although all so tested were unloaded by maximal motor nerve twitches. Reasons are given for thinking that such apparent lack of parallel coupling is an artifact of complex intramuscular anatomy and limitation of shortening by ;isometric' myography.3. A brief burst of corticospinal volleys at 500/sec, which is specially effective in exciting alpha motoneurones over the CM projection, failed to excite spindle afferents at or below the threshold for a cortical ;twitch'.4. In a few epileptiform discharges, bursts of spindle acceleration occurred independently of the clonic contractions. A relatively direct and independent cortico-fusimotor (CF) projection may therefore exist.5. Prolonged near-threshold stimulation at 50-100/sec, which allows time for temporal summation in the less direct projections (e.g. cortico-interneuronal, cortico-rubro-spinal) and does not cause frequency-potentiation at CM synapses, gives abundant evidence of independent alpha and fusimotor projections, whose actions hardly outlast the stimulation period.6. Although independent CF projections would permit servo-driving in natural movements of the hand (given adequate loop gain), there has been no evidence of servo-driving by cortical stimulation or in the spontaneous contractions of light anaesthesia.7. Independent projections would provide for controlled alphagamma co-excitation in the servo-governing of natural movements (Matthews, 1964).8. Evidence is reviewed that the CM projection itself may be part of an important control loop for voluntary movement in primates. A corollary would be a diminished importance of CF projections for segmental loops and an increased importance for maintaining the spindle input to cortical loops.

Action Potentials↗

PubMed1975

Motor control of nuclear bag and nuclear chain intrafusal fibres in isolated living muscle spindles from the cat.

1. The behaviour of nuclear bag and nuclear chain intrafusal fibres in isolated cat muscle spindles was studied by direct observation during repetitive stimulation of the muscle nerve at different stimulus strengths. Contraction of intrafusal fibres and stretch of sensory endings was recorded on film. 2. Tenuissimus spindles are usually operated by a total of four or five fusimotor axons, and the individual action of all of them was studied in many cases. 3. The great majority of fusimotor axons produce activity at one spindle pole only. 4. In about 60% of spindles nuclear bag and nuclear chain intrafusal fibres are selectively controlled by different fusimotor axons, while in one third of these spindles the individual nuclear bag fibres are themselves controlled independently. The remaining 40% of spindles, in addition to some selective innervation, receive one non-selective axon which operates both nuclear chain and nuclear bag fibres though usually only one of the nuclear bag fibres is involved. Selective control is demonstrated in photographs. 5. The thresholds of fusimotor axons selectively innervating nuclear bag and nuclear chain fibres, and of non-selective fusimotor axons are not significantly different. 6. It is suggested that in spindles in which the nuclear bag fibres are controlled by the same axon, it is a 'dynamic' gamma, or occasionally beta, axon. Where one nuclear bag fibre is operated along with the nuclear chain fibres it is controlled by 'static' gamma axon(s), and the other nuclear bag fibre is selectively controlled by 'dynamic' gamma, and perhaps beta, axon(s). Where two nuclear bag fibres are separately operated one may be controlled by 'dynamic' axon(s) and the other by 'static' gamma axon(s). Nuclear chain fibres are always controlled by 'static' gamma axons.

Action Potentials↗

PubMed1990

Fusimotor control of muscle spindle sensitivity during respiration in the cat.

1. The two types of fusimotor neurones, dynamic and static, can be differentiated by their effects on muscle spindle afferents. We have recorded the activity of muscle spindle primary afferents from the intercostal nerves of anaesthetized or decerebrate cats. A 4 Hz sinusoidal stretch was applied to the muscle containing the spindles of interest before and after crushing the nerve proximal to the recording site to eliminate fusimotor effects. The relative activity of the dynamic and static fusimotor neurones was inferred from the change in the spindle afferents' response. 2. Some areas of intercostal muscle normally showed phasic activity linked to respiration, where as other areas of intercostal muscle showed no EMG activity under our experimental conditions. In areas of intercostal muscle lacking EMG activity, the afferents' mean rate was higher and the modulation around the mean was lower at all phases of the breathing cycle when the efferent supply was intact. This result suggests the muscle spindles were receiving a steady level of static fusimotor activity. 3. Spindle primary afferents from regions of intercostal muscle that were typically recruited during respiration had an additional increase in mean rate and modulation around the mean rate in phase with the EMG activity. This is suggestive of phasic activation of dynamic fusimotor neurones in addition to static fusimotor discharge. 4. Thus, the two types of fusimotor neurones can be activated separately by the CNS to control the sensitivity of muscle spindles. The regional differences in the recruitment patterns of fusimotor neurones parallels the functional specializations of different areas of the intercostal muscles. The temporal modifications of fusimotor activity during each respiratory cycle means that the segmental reflex gain will vary in those intercostal muscles that are active during respiration. 5. These findings regarding the CNS recruitment of the two types of fusimotor neurones during respiration are similar to those reported for the hindlimb extensors during locomotion, but differ from those reported for jaw muscles during chewing. This may reflect differing control strategies being used by the CNS to meet the unique demands of the various rhythmical movements.

Action Potentials↗

PubMed2002

Contractile properties of isolated muscle spindles of the frog.

Force and isotonic shortening velocities were studied (0.6-4.0 degrees C) in isolated single muscle spindles from the anterior tibialis muscle of Rana temporaria using techniques that enabled measurements both from the spindle as a whole and from marked segments of the preparation. The force-velocity relationship during tetanic stimulation exhibited the same biphasic shape as previously described for extrafusal muscle fibres. However, the maximum speed of shortening of the spindle fibres was merely 0.95 +/- 0.006 lengths s(-1) (mean +/- S.E.M., n = 11), which is approximately half the value recorded in extrafusal fibres of the same muscle. The maximum tetanic force, 91 +/- 10 kN m(-2), n = 14, was likewise only approximately half that produced by extrafusal fibres. The force generated by the capsule segment was lower than that produced by the whole spindle resulting in elongation of the capsule region during a fixed-end tetanus. The intracellular calcium ion concentration reached during the plateau of the tetanus, 1.7 +/- 0.1 microM (n = 8), was substantially lower than the value attained in extrafusal fibres under equivalent conditions. In accordance, the spindle fibres did not become fully activated during supramaximal electrical stimulation as indicated by the finding that the tetanic force could be further increased by 16.6 +/- 0.04 % (n = 5) on addition of 0.5 mM caffeine. Inadequate activation may thus, to a certain extent, account for the relatively low force per cross-sectional area of the spindle fibres. The contractile properties of the intrafusal fibres should make the spindle organ suited to provide feedback control during eccentric (forced lengthening) and static (isometric) contractions and, with reduced effectiveness, during slow muscle shortening.

Algorithms↗

PubMed2005

Vertebral position alters paraspinal muscle spindle responsiveness in the feline spine: effect of positioning duration.

Proprioceptive information from paraspinal tissues including muscle contributes to neuromuscular control of the vertebral column. We investigated whether the history of a vertebra's position can affect signalling from paraspinal muscle spindles. Single unit recordings were obtained from muscle spindle afferents in the L6 dorsal roots of 30 Nembutal-anaesthetized cats. Each afferent's receptive field was in the intact muscles of the low back. The L6 vertebra was controlled using a displacement-controlled feedback motor and was held in each of three different conditioning positions for durations of 0, 2, 4, 6 and 8 s. Conditioning positions (1.0-2.2 mm dorsal and ventral relative to an intermediate position) were based upon the displacement that loaded the L6 vertebra to 50-60% of the cat's body weight. Following conditioning positions that stretched (hold-long) and shortened (hold-short) the spindle, the vertebra was repositioned identically and muscle spindle discharge at rest and to movement was compared with conditioning at the intermediate position. Hold-short conditioning augmented mean resting spindle discharge by +4.1 to +6.2 impulses s(-1); however, the duration of hold-short did not significantly affect this increase (F(4,145) = 0.49, P = 0.74). The increase was maintained at the beginning of vertebral movement but quickly returned to baseline. Conversely, hold-long conditioning significantly diminished mean resting spindle discharge by -2.0 to -16.1 impulses s(-1) (F(4,145) = 11.23, P < 0.001). The relationship between conditioning duration and the diminished resting discharge could be described by a quadratic (F(1,145) = 9.28, P = 0.003) revealing that the effects of positioning history were fully developed within 2 s of conditioning. In addition, 2 s or greater of hold-long conditioning significantly diminished spindle discharge to vertebral movement by -5.7 to -10.0 impulses s(-1) (F(4,145) = 11.0, P < 0.001). These effects of vertebral positioning history may be a mechanism whereby spinal biomechanics interacts with the spine's proprioceptive system to produce acute effects on neuromuscular control of the vertebral column.

Action Potentials↗

PubMed2006

Dynamic localization of the human papillomavirus type 11 origin binding protein E2 through mitosis while in association with the spindle apparatus.

Papillomaviral DNA replicates as extrachromosomal plasmids in squamous epithelium. Viral DNA must segregate equitably into daughter cells to persist in dividing basal/parabasal cells. We have previously reported that the viral origin binding protein E2 of human papillomavirus types 11 (HPV-11), 16, and 18 colocalized with the mitotic spindles. In this study, we show the localization of the HPV-11 E2 protein to be dynamic. It colocalized with the mitotic spindles during prophase and metaphase. At anaphase, it began to migrate to the central spindle microtubules, where it remained through telophase and cytokinesis. It was additionally observed in the midbody at cytokinesis. A peptide spanning residues 285 to 308 in the carboxyl-terminal domain of HPV-11 E2 (E2C) is necessary and sufficient to confer localization on the mitotic spindles. This region is conserved in HPV-11, -16, and -18 and bovine papillomavirus type 4 (BPV-4) E2 and is also required for the respective E2C to colocalize with the mitotic spindles. The E2 protein of bovine papillomavirus type 1 is tethered to the mitotic chromosomes via the cellular protein Brd4. However, the HPV-11 E2 protein did not associate with Brd4 during mitosis. Lastly, a chimeric BPV-1 E2C containing the spindle localization domain from HPV-11 E2C gained the ability to localize to the mitotic spindles, whereas the reciprocal chimera lost the ability. We conclude that this region of HPV E2C is critical for localization with the mitotic apparatus, enabling the HPV DNA to sustain persistent infections.

Animals↗

PubMed2006

The spindle assembly checkpoint regulates the phosphorylation state of a subset of DNA checkpoint proteins in Saccharomyces cerevisiae.

The DNA and the spindle assembly checkpoints play key roles in maintaining genomic integrity by coordinating cell responses to DNA lesions and spindle dysfunctions, respectively. These two surveillance pathways seem to operate mostly independently of one another, and little is known about their potential physiological connections. Here, we show that in Saccharomyces cerevisiae, the activation of the spindle assembly checkpoint triggers phosphorylation changes in two components of the DNA checkpoint, Rad53 and Rad9. These modifications are independent of the other DNA checkpoint proteins and are abolished in spindle checkpoint-defective mutants, hinting at specific functions for Rad53 and Rad9 in the spindle damage response. Moreover, we found that after UV irradiation, Rad9 phosphorylation is altered and Rad53 inactivation is accelerated when the spindle checkpoint is activated, which suggests the implication of the spindle checkpoint in the regulation of the DNA damage response.

Cell Cycle Proteins↗

PubMed2003

Recognizing chromosomes in trouble: association of the spindle checkpoint protein Bub3p with altered kinetochores and a unique defective centromere.

Spindle checkpoint proteins monitor the interaction of the spindle apparatus with the kinetochores, halting anaphase even if the microtubule attachment of only a single chromosome is altered. In this study, we show that Bub3p of Saccharomyces cerevisiae, an evolutionarily conserved spindle checkpoint protein, exhibits distinct interactions with an altered or defective kinetochore(s). We show for the first time that green fluorescent protein-tagged S. cerevisiae Bub3p (Bub3-GFP) exhibits not only a diffuse nuclear localization pattern but also forms distinct nuclear foci in unperturbed growing and G(2)/M-arrested cells. As Bub3-GFP foci overlap only a subset of kinetochores, we tested a model in which alterations or defects in kinetochore or spindle integrity lead to the distinct enrichment of Bub3p at these structures. In support of our model, kinetochore-associated Bub3-GFP is enriched upon activation of the spindle checkpoint due to nocodazole-induced spindle disassembly, overexpression of the checkpoint kinase Mps1p, or the presence of a defective centromere (CEN). Most importantly, using a novel approach with the chromatin immunoprecipitation (ChIP) technique and genetically engineered defective CEN [CF/CEN6(Delta31)], we determined that Bub3-GFP can associate with a single defective kinetochore. Our studies represent the first comprehensive molecular analysis of spindle checkpoint protein function in the context of a wild-type or defective kinetochore(s) by use of live-cell imaging and the ChIP technique in S. cerevisiae.

Base Sequence↗

PubMed2005

The role of centromere-binding factor 3 (CBF3) in spindle stability, cytokinesis, and kinetochore attachment.

The spindle midzone is critical for spindle stability and cytokinesis. Chromosomal passenger proteins relocalize from chromosomes to the spindle midzone after anaphase onset. The recent localization of the inner-kinetochore, centromere-binding factor 3 (CBF3) complex to the spindle midzone in budding yeast has led to the discovery of novel functions for this complex in addition to its essential role at kinetochores. In G1/S cells, CBF3 components are detected along dynamic microtubules, where they can "search-and-capture" newly replicated centromeres. During anaphase, CBF3 is transported to the microtubule plus-ends of the spindle midzone. Consistent with this localization, cells containing a mutation in the CBF3 subunit Ndc10p show defects in spindle stability during anaphase. In addition, ndc10-1 cells show defects during cytokinesis, resulting in a defect in cell abscission. These results highlight the importance of midzone-targeted proteins in coordinating mitosis with cell division. Here we discuss these findings and explore the significance of CBF3 transport to microtubule plus-ends at the spindle midzone.

Cell Cycle↗

PubMed1996

Genetic analysis of the mitotic spindle.

Much of our understanding of the molecular basis of mitotic spindle function has been achieved within the past decade. Studies utilizing genetically tractable organisms have made important contributions to this field and these studies form the basis of this review. We focus upon three areas of spindle research: spindle poles, centromeres, and spindle motors. The structure and duplication mechanisms of spindle poles are considered as well as their roles in organizing spindle microtubules. Centromeres vary considerably in their size and complexity. We describe recent progress in our understanding of the relatively simple centromeres of the yeast Saccharomyces cerevisiae and the complex centromeres that are more typical of eukaryotic cells. Microtubule-based motor proteins that generate the characteristic spindle movements have been identified in recent years and can be grouped into families defined by conserved primary sequence and mitotic function.

Animals↗

PubMed2003

Spindle model responsive to mixed fusimotor inputs and testable predictions of beta feedback effects.

Skeletofusimotor (beta) motoneurons innervate both extrafusal muscle units and muscle fibers within muscle spindle stretch receptors. By receiving excitation from group Ia muscle spindle afferents and driving the muscle spindle afferents that excite them, they form a positive feedback loop of unknown function. To study it, we developed a computationally efficient model of group Ia afferent behavior, capable of responding to multiple fusimotor inputs, that matched experimental data. This spindle model was then incorporated into a simulation of group Ia feedback during ramp/hold and triangular stretches with and without closure of the beta loop, assuming that gamma and beta fusimotor drives of the same type (static or dynamic) have identical effects on spindle afferent firing. The effects of beta feedback were implemented by driving a fusimotor input with a delayed and filtered fraction of the spindle afferent output. During triangular stretches, feedback through static beta motoneurons enhanced Ia afferent firing during shortening of the spindle. In contrast, closure of a dynamic beta loop increased Ia firing during lengthening. The strength of beta feedback, estimated as a "loop gain" was comparable to experimental estimates. The loop gain increased with velocity and amplitude of stretch but decreased with increased superimposed gamma fusimotor rates. The strongest loop gains were seen when the beta loop and the gamma bias were of different types (static vs. dynamic).

Algorithms↗