High-fidelity evoked potential for mapping the rat tail in thalamus

The technique of field potentials (FPs) provides a macroscopic view for exploring brain function, and is supplementary to single-unit recording, a microscopic view that investigates each neuron in great detail. Mapping the rat tail in the ventroposterolateral (VPL) nucleus of the thalamus was carried out by analyzing the current source density (CSD) of the evoked FPs. The results showed a clear somatotopic organization of the tail in the VPL nucleus. Also, to obtain high-fidelity FPs, two recording parameters were determined. Based upon cross-correlation coefficient (rho), the cycles of FPs needed to be averaged should not be less than 50 and the distance between the two recording sites should be no longer than 50 mum in each direction (mediolateral, anteroposterior and ventrodorsal). Under these conditions, the representation (or reproducibility) of an FP can be >95%. The procedures used to determine these parameters can serve as a guide to obtain FPs with high signal-to-noise ratio and without spatial aliasing error.     

Physiology of the fasciculation potentials in amyotrophic lateral sclerosis: which motor units fasciculate?

We set out to study whether in amyotrophic lateral sclerosis (ALS) fasciculation potentials (FPs) arise from the most excitable motor units (MUs). We studied 70 patients with ALS and 18 subjects with benign fasciculation syndrome (BFS). Of the 56 eligible ALS patients, 31 had signs of reinnervation in the right first dorsal interosseous muscle selected for study, and 25 did not. Two needle electrodes were placed in different MUs in each studied muscle. We defined the most excitable MU as that first activated by minimal voluntary contraction. In muscles without reinnervation, the recording site with most frequent FPs had a higher probability of showing the first recruited MU (p < 0.001). No significant difference was found in other patients or in BFS subjects. In very early affected muscles, fasciculating MUs are the most likely to be recruited volitionally. This probably represents hyperexcitability at lower motor neuronal level.     

Fiducial points for three-dimensional computer-assisted reconstruction of serial light microscopic sections of umbilical cord

Fascicles of human sural (peripheral sensory) nerve were used as external fiducial points (FP) for accurate registration of serial light microscopic sections in three-dimensional reconstruction of human umbilical cord. This paper describes a method for embedding the FPs within the paraffin wax block simultaneously with the specimen to be sectioned. Using a new design of embedding box, the FPs are embedded close to the specimen and are transferred to the slides as part of the tissue sections. Three to four FPs were used to align and scale the serial tissue sections for digitization and computerized reconstruction, using a commercially available software program on IBM-compatible 80386 hardware. A three-dimensional solid surface graphic model of a segment of human umbilical cord was generated.     

Effect of nerve length and temperature on the induction of action potentials in denervated slow muscle fibres of the frog

A. Pyriformis and extensor longus digiti IV muscles of Rana temporaria were denervated by cutting the sciatic or peroneal nerve at various distances from the muscles. Slow fibres were identified by their membrane time constants, and examined for their ability to produce action potentials in response to intracellularly applied current pulses. B. The slow muscle fibres acquired the ability to generate action potentials several days after denervation. The duration of this latent period depended on the length of the peripheral nerve stump, and on the temperature at which the frogs were kept after the operation. C. At 18 degrees C the latent period increased by 0.36 days per mm of sciatic nerve stump. At 11.5 degrees C the corresponding value was 0.7 days/mm. The effect of length of the peroneal nerve was smaller than that of the sciatic nerve. D. It is suggested that the peripheral nerve stump serves as a reservoir of 'trophic' material which is transported towards the slow fibres at a rate of 2.8 mm/day (at 18 degrees C) and seems to block the formation of Na channels. The Q10 value of this transport system would be 2.7.     

臀部肌注致坐骨神经损伤的神经电生理分析

目的：研究臀部肌注致坐骨神经损伤后患肢的运动传导速度和肌电图的改变。方法：回顾性分析65名臀部肌注致坐骨神经损伤患者的患侧腓总神经和胫神经的运动传导速度及胫前肌和腓肠肌的针极肌电图检查。结果：65例中，患侧胫神经异常者15例（23．1％），患侧腓总神经异常者40例（61．5％）。肌注后5天内运动传导速度异常率低于5天后的异常率。患侧胫前肌异常者9例（13．8％），患侧腓肠肌异常者7例（10．8％）。结论：运动神经传导速度和肌电图检查是臀部肌注致坐骨神经损伤的不可缺少的神经电生理指标。     

Long-term potentiation in slices of kitten visual cortex and the effects of NMDA receptor blockade.

1. A slice preparation was used to study layer III field potentials (FPs) evoked by electrical stimulation of the white matter-layer VI border and their potentiation by patterned stimuli. 2. The dependence of the FP on recording position was investigated. The maximum field was recorded in layer III at a position radial to the site of stimulation. Because this negative FP reflects an excitatory synaptic current sink, this site was chosen for all subsequent experiments. 3. Under normal recording conditions, components of the layer III FP with latencies greater than 3 ms were completely abolished by kynurenate but unaffected by 2-amino-5-phosphonovalerate (AP5), indicating that this potential reflects the activation of non-NMDA excitatory amino acid receptors. 4. Addition of the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline methiodide (BMI) broadened the field potential and revealed an AP5-sensitive component. By filling the recording pipette with BMI, it was possible to substantially reduce inhibition locally around the recording site while avoiding stimulus-driven and spontaneous epileptiform activity. 5. Tetanic stimulation elicited a long-term potentiation (LTP) of the FP in 14 of 17 experiments when the BMI-filled pipette method was used. 6. Addition of 100 microM D,L-AP5 significantly reduced the average probability and magnitude of LTP. Nonetheless, in 2 of 8 experiments, significant LTP was observed after a tetanus in the presence of AP5. Control experiments confirmed that this concentration of AP5 was sufficient to maximally block cortical NMDA receptors. 7. We conclude that LTP of layer III field potentials can be reliably elicited, provided that GABAA-receptor mediated inhibition is blocked locally at the site of recording and that NMDA receptors are recruited during the conditioning stimulation. However, activation of NMDA receptors is apparently not an obligatory step for the induction of use-dependent increases in synaptic strength in the kitten striate cortex.     

Segmental hypermobility in lumbar spine and entrapment of dorsal rami

Low back pain patients (N = 18) having segmental hypermobility in one lumbar segment and healthy controls (N = 13) were chosen for this study. Patients had no other structural spinal pathology except displacement of one vertebra to another in lateral X-ray bending pictures. Kinetic intramuscular EMG-activity from paraspinal muscles was studied off-line during back flexion and reextension. Routine needle EMG study of paraspinal muscles was also performed in addition to measurements of the tibial nerve H-reflexes and peroneal F-responses. Results showed that the number of MUAPs in erector spinae muscle on voluntary efforts was rarefied at hypermobile levels, and spontaneous activity, positive sharp waves and high frequency discharges were found in more than half of the patients in paraspinal muscles, usually at hypermobile levels only. No signs of proximal nerve root compression were found. This indicates neuropathy of dorsal rami at the instable level.     

A Methodology for Detecting Field Potentials from the External Ear Canal: NEER and EVestG

An algorithm called the neural event extraction routine (NEER) and a method called Electrovestibulography (EVestG) for extracting field potentials (FPs) from artefact rich and noisy ear canal recordings is presented. Averaged FP waveforms can be used to aid detection of acoustic and or vestibular pathologies. FPs were recorded in the external ear canal proximal to the ear drum. These FPs were extracted using an algorithm called NEER. NEER utilises a modified complex Morlet wavelet analysis of phase change across multiple scales and a template matching (matched filter) methodology to detect FPs buried in noise and biological and environmental artefacts. Initial simulation with simulated FPs shows NEER detects FPs down to -30 dB SNR (power) but only 13-23% of those at SNR's <-6 dB. This was deemed applicable to longer duration recordings wherein averaging could be applied as many FPs are present. NEER was applied to detect both spontaneous and whole body tilt evoked FPs. By subtracting the averaged tilt FP response from the averaged spontaneous FP response it is believed this difference is more representative of the vestibular response. Significant difference (p < 0.05) between up and down whole body (supine and sitting) movements was achieved. Pathologic and physiologic evidence in support of a vestibular and acoustic origin is also presented.     

Denervated muscle: rate of propagation and effects of manganese ions and glycerol on the fibrillatory activity of frog semitendinosus

Denervated frog's semitendinosus muscles were studied. Fibrillation potentials generate propagated spikes which are conducted at a rate similar to that calculated for innervated muscles. The twitch tension per unit area was similar in denervated and innervated single fibres; the average value corresponded with values reported in the literature for fibres stimulated at 125/sec. Manganese ions (1-3 mM), selectively inhibit fibrillation potentials and have no appreciable effect upon evoked spikes. Mn2+ also inhibits (40-50%) the twitch responses and abolishes the resting tension of muscle fibres. The latter effects were observed in denervated as well as in innervated preparations when the fibres studied belonged to fasicles located at the site of entrance of the nerve. Disruption of the transverse tubular system by glycerol treatment does not interfere with the generation of fibrillation potentials, although the effects on twitching are similar to those reported in the literature. A possible mechanism is proposed to explain the generation of fibrillation potentials in frog denervated muscles.     

Specificity of electrical coupling among neurons innervating forelimb muscles of the adult bullfrog

1. The specificity of electrical connections among sensory fibers and motoneurons in the bullfrog's spinal cord was studied by recording intracellularly from brachial motoneurons. Synaptic potentials evoked by stimulation of individual muscle nerves were recorded in normal and reduced-calcium solutions and after acute section of dorsal or ventral roots. 2. Homonymous motoneurons are electrically coupled. After the dorsal roots were cut to abolish sensory input, short-latency potentials were almost always evoked anti-dromically in a motoneuron by stimulation of its own muscle nerve but rarely by stimulation of nerves innervating other muscles. These potentials differed from chemically mediated synaptic potentials in this preparation; they had a shorter latency and remained after perfusion with reduced-calcium solutions. This evidence suggests that they are mediated electrically. 3. Some motoneurons that innervate functionally equivalent muscles are electrically coupled. Approximately two-thirds of the motoneurons innervating the internal or external heads of the triceps muscles received coupling potentials on stimulation of the other nerve, although never on stimulation of the heteronymous, medial, triceps nerve. 4. The monosynaptic potentials evoked by muscle sensory afferents in motoneurons often have both electrical and chemical components. The electrical component occurred with short delay and persisted in reduced-calcium solutions. The chemical component occurred 1.5-2.0 ms later, at 14 degrees C, and was abolished by reducing calcium in the bathing solution. Muscle sensory afferents make these mixed synapses on homonymous, heteronymous, and other motoneurons.     

Automated breast mass detection in 3D reconstructed tomosynthesis volumes: a featureless approach

The purpose of this study was to propose and implement a computer aided detection (CADe) tool for breast tomosynthesis. This task was accomplished in two stages-a highly sensitive mass detector followed by a false positive (FP) reduction stage. Breast tomosynthesis data from 100 human subject cases were used, of which 25 subjects had one or more mass lesions and the rest were normal. For stage 1, filter parameters were optimized via a grid search. The CADe identified suspicious locations were reconstructed to yield 3D CADe volumes of interest. The first stage yielded a maximum sensitivity of 93% with 7.7 FPs/breast volume. Unlike traditional CADe algorithms in which the second stage FP reduction is done via feature extraction and analysis, instead information theory principles were used with mutual information as a similarity metric. Three schemes were proposed, all using leave-one-case-out cross validation sampling. The three schemes, A, B, and C, differed in the composition of their knowledge base of regions of interest (ROIs). Scheme A's knowledge base was comprised of all the mass and FP ROIs generated by the first stage of the algorithm. Scheme B had a knowledge base that contained information from mass ROIs and randomly extracted normal ROIs. Scheme C had information from three sources of information-masses, FPs, and normal ROIs. Also, performance was assessed as a function of the composition of the knowledge base in terms of the number of FP or normal ROIs needed by the system to reach optimal performance. The results indicated that the knowledge base needed no more than 20 times as many FPs and 30 times as many normal ROIs as masses to attain maximal performance. The best overall system performance was 85% sensitivity with 2.4 FPs per breast volume for scheme A, 3.6 FPs per breast volume for scheme B, and 3 FPs per breast volume for scheme C.     

Spinal somatostatin superfusion in vivo affects activity of cat nociceptive dorsal horn neurons: comparison with spinal morphine

A controversy exists concerning the role of the neuropeptide somatostatin for the transmission or inhibition of nociceptive information in the spinal cord. To better correlate electrophysiological effects of somatostatin at single cell level with results obtained with intrathecal injections of somatostatin in behaving animals and human pain patients we applied somatostatin to the spinal cord by controlled superfusion of the recording segment in vivo. The hypothesis of an opioid link and possible neurotoxic effects of somatostatin were also addressed. In cats deeply anaesthetized with pentobarbitone, halothane and nitrous oxide, extracellular recordings were made from 27 neurons located in laminae I-VI. All neurons responded to both innocuous mechanical and noxious radiant heat stimuli applied to the glabrous skin of the ipsilateral hindpaw. The dorsal surface of the spinal cord was superfused at the recording segment by means of a Perspex chamber (7 x 7 mm). Somatostatin superfusions at 1.2 microM had no effect on responses to noxious heat. Responses were, however, depressed by somatostatin at 61 microM to 59.7 +/- 5.1% of control and by somatostatin at 1.53 mM to 39.9 +/- 9.5% of control. This inhibition was not antagonized by the mu-opiate antagonist naloxone applied to the spinal cord at concentrations of 2.7 mM, either together with somatostatin, or after the inhibition by somatostatin had fully developed. Neuronal responses were linear functions of the skin temperatures for stimulation intensities between 42 degrees C and 52 degrees C. The slopes of these stimulus response functions were reduced during somatostatin superfusion at 61 microM to 46.8 +/- 9.3% of control, without changing the temperature thresholds for responding (42.5 +/- 0.6 degrees C). Somatostatin superfusion at 61 microM had no effect on the number of action potentials evoked by innocuous skin brushing, or by electrical stimulation of primary afferent A-fibres in cutaneous nerves. The amplitude of intraspinally recorded field potentials evoked by these electrical nerve stimuli was also unaffected by somatostatin. The inhibition of nociceptive spinal dorsal horn neurons by spinally administered morphine was assessed in eight experiments. Morphine reduced noxious heat-evoked responses to 42.1 +/- 9.6% of control at 0.3 mM and to 51.8 +/- 6.9% of control at 3.0 mM. The slopes of the stimulus-response functions were reduced by morphine at 0.3 mM to 53.1 +/- 11.3% of control, without changing the temperature thresholds (42.7 degrees C). Naloxone superfusion (2.7 mM) reliably antagonized the inhibition by morphine. Brush-evoked responses were not, or much less, affected by spinal morphine.(ABSTRACT TRUNCATED AT 400 WORDS)     

Electrophysiological studies of neuromuscular transmission in hereditary `motor end-plate disease' of the mouse

1. Studies have been made on isolated nerve-muscle preparations from mice with hereditary ;motor end-plate disease'.2. Spontaneous fibrillation was observed in the isolated preparation.3. Muscles gave only a weak twitch or failed to contract in response to nerve stimulation. Direct stimulation of muscles caused a twitch response which had a slower time course than normal. Peripheral nerve conduction was normal.4. Intracellular recording from single muscle fibres showed that with longer survival of the animal an increasing proportion of fibres failed to show end-plate potentials or action potentials in response to nerve stimulation.5. Miniature end-plate potentials (m.e.p.p.s) were recorded in almost all muscle fibres including those in which neuromuscular transmission had failed. The frequency of m.e.p.p.s was greater than normal, was not increased by tetanic stimulation of the nerve but was increased by a raised external potassium concentration.6. Muscle fibres were supersensitive to acetylcholine.7. The results suggest that the muscular weakness in this disease is due to the failure of nerve action potentials to invade motor nerve terminals so that muscle fibres become ;functionally denervated'.     

Spinal evoked potentials evaluated with two relevant electrode types

The spinal evoked potentials (SEPs) were recorded at the level of the 7th lumbar segment in five cats by stimulating the popliteal nerve separately on both sides. The recordings were performed both with silver-silver chloride cup electrodes and stainless steel needle electrodes. The shapes and latencies of the responses were highly similar, when comparing the responses recorded with the two electrode types. These similarities are explained by similar recording properties of both electrode types as shown by means of transfer function: attenuation and phase curves for both electrode types are highly similar in the bandpass used in the present study. It is concluded that the properties of stainless steel needle electrodes are highly correspondent with the conventional silver-silver chloride electrodes when somatosensory evoked responses are recorded.     

Relationships between motor unit size and recruitment threshold in older adults: implications for size principle

As a part of the aging process, motor unit reorganization occurs in which small motoneurons reinnervate predominantly fast-twitch muscle fibers that have lost their innervation. We examined the relationship between motor unit size and the threshold force for recruitment in two muscles to determine whether older individuals might develop an alternative pattern of motor unit activation. Young and older adults performed isometric contractions ranging from 0 to 50% of maximal voluntary contraction in both the first dorsal interosseous (FDI) and tibialis anterior (TA) muscles. Muscle fiber action potentials were recorded with an intramuscular needle electrode and motor unit size was computed using spike-triggered averaging of the global EMG signal (macro EMG), which was also obtained from the intramuscular needle electrode. As expected, older individuals exhibited larger motor units than young subjects in both the FDI and the TA. However, moderately strong correlations were obtained for the macro EMG amplitude versus recruitment threshold relationship in both the young and older adults within both muscles, suggesting that the size principle of motor unit recruitment seems to be preserved in older adults.     

Nerve conduction studies of suprascapular nerve for site-of-lesion diagnosis

Shoulder pain is a common symptom, resulting not only from bone and shoulder joint diseases, but also from neurogenic lesions. Entrapment neuropathy of the suprascapular nerve also causes shoulder symptoms. Conduction of the suprascapular nerve was studied in 12 healthy control subjects and 25 patients suffering from shoulder pain and/or dysfunction. Surface stimulation was performed at Erb's point, and compound muscle action potentials(M waves) were recorded from the supraspinatus and the infraspinatus muscles with concentric needle electrodes. To determine the optimal site for recording M waves from the infraspinatus muscle, simultaneous multi-channel recordings of M waves using pairs of surface electrodes were obtained from different sites over the infraspinatus muscle. In two patients, latency of the M waves to the infraspinatus muscle was prolonged, whereas that to the supraspinatus muscle was normal. These findings indicate entrapment neuropathy at the spinoglenoid notch. In three patients, the latency to the infraspinatus and supraspinatus muscles was prolonged. These findings are compatible with entrapment neuropathy at the suprascapular notch. The latency to the supraspinatus and infraspinatus muscles was prolonged in patients with brachial plexus injury and in those with suprascapular nerve injury. In patients with myopathy, those with neuralgic amyotrophy and those with cervical radiculopathy, the latency was normal. Thus, conduction studies of the suprascapular nerve using multiple-channel recordings are useful, especially for the diagnosis of entrapment neuropathy of the suprascapular nerve.     

Manual acupuncture needle stimulation of the rat hindlimb activates groups I, II, III and IV single afferent nerve fibers in the dorsal spinal roots

Using single unit nerve recording techniques in rats, the present experiment aimed to determine which specific population of afferent nerve fibers (groups I, II, III and IV) in the dorsal roots at the 4th or 5th lumbar segments (L4 or L5) are activated during manual acupuncture needle stimulation. An acupuncture needle 300-340 microm in diameter was inserted into the skin and underlying muscles around the Zusanli acupoint (ST36) area in the hindlimbs, and was manually rotated right and left at a frequency of about 1 Hz for 1 min. The dorsal root of the L4 and L5 spinal nerve was cut close to the entrance into the spinal cord after laminectomy and dissected free to record unitary afferent nerve activity. A single afferent fiber activated by acupuncture stimulation was identified by the identical shape of the discharge spikes during stimulation and during electrically evoked action potentials induced by single pulse electrical stimulation of the sciatic nerve. The conduction velocity of the afferent fiber was calculated by the latency of the electrically evoked action potential. A total of 35 units were intentionally recorded from all animals in order to include all 4 afferent fiber groups. Units were spontaneously silent in the absence of stimulation, while all units responded to ipsilateral manual rotation of the acupuncture needle. The conduction velocity of all 35 units ranged between 0.8 and 86.0 m/s, thus belonging to groups I-V fibers. Mean conduction velocity of groups I, II, III and IV were 57.9 m/s (n = 13), 42.9 m/s (n = 11), 10.3 m/s (n = 6) and 1.2 m/s (n = 5), respectively. Mean discharge rates during acupuncture stimulation of groups I, II, III and IV afferents were 7.4 Hz, 6.2 Hz, 4.7 Hz and 0.4 Hz, respectively. Discharge rates of group IV afferent fibers were significantly lower than those of groups I, II and III afferents. It was concluded that manual acupuncture needle stimulation to the hindlimbs activated afferent nerve fibers belonging to all four groups of afferents in rats. It is suggested that all four groups of somatic afferents activated by manual acupuncture stimulation will elicit various effects when action potentials are delivered to the central nervous system.     

Carpal tunnel syndrome: comparison of the compound muscle action potentials recorded at the thenar region from ulnar and median nerve stimulation

Thenar muscles are primarily innervated by the median nerve. However, compound muscle action potentials (CMAPs) evoked by ulnar nerve stimulation can be recorded at the thenar region due to proximity of some ulnar-innervated muscles, and from volume conduction events. This study was to determine if loss of thenar muscle mass from carpal tunnel syndrome (CTS) could alter the size of ulnar CMAPs obtained at the thenar region, because of changes in the physical surroundings and electrical conductivity. Supramaximal CMAPs were recorded over the thenar eminence to electrical stimulation of the ulnar nerve at the wrist and median nerve at the palm in 102 hands with CTS. Needle EMG was done in the thenar muscles. Severity of needle EMG abnormality was negatively correlated with median-evoked CMAP amplitude (r = -0.76), but not with ulnar-evoked CMAP amplitude (r = -0.12). There was no correlation between the absolute amplitudes of the median and ulnar CMAPs (r = -0.13). Needle EMG abnormality had modest negative correlation (r = -0.43) with median/ulnar CMAP amplitude ratio. Mean median/ulnar CMAP amplitude ratios for normal EMG and for mild, moderate, and severe needle EMG abnormalities were 3.72, 3.31, 1.56, and 0.37, respectively. The absolute amplitude of the ulnar CMAP recorded at the thenar area does not seem to be influenced significantly by the degree of thenar muscle loss (atrophy) from median nerve pathology. However, if the median/ulnar CMAP amplitude ratio falls below 0.5, the study suggests severe loss of motor units in the thenar muscles.     

A comparison of fibrillation in denervated skeletal muscle of the anaesthetized rat and guinea-pig

Summary We have used intracellular recordingin vivo to study fibrillation (spontaneous repetitive membrane activity) in extensor digitorum longus (fast twitch) and soleus (slow twitch) muscles of the anaesthetized rat and guinea-pig denervated for periods of about 10 to 60 days. The proportion of fibres fibrillating in the guinea-pig soleus was greater than 50% in most animals up to the longest period of denervation (65 days). Fibrillation was rarely found in rat soleus after three weeks of denervation. Its incidence in the extensor digitorum longus muscles of both species was intermediate. The mean frequency of fibrillation was higher in guinea-pig extensor digitorum longus (16 Hz) and soleus (8 Hz) than in the rat extensor digitorum longus (3 Hz) and soleus (2 Hz). The resting membrane potentials of the denervated muscles were less than normal and correlated inversely with the frequency of fibrillation but not with the incidence of fibrillation: in rat soleus, many fewer fibres were fibrillating at a given membrane potential than in the other three muscles. The incidence of fibrillation was compared with previously reported tensions of the four denervated muscles and was found to have the same rank order. We suggest that fibrillation may reduce atrophy (and hence tension loss) of denervated muscle, which may have implications for artificial stimulation. Fibrillation frequency was directly related to changes in twitch speed of the four muscles after denervation.     

Dimerization between aequorea fluorescent proteins does not affect interaction between tagged estrogen receptors in living cells

Forster resonance energy transfer (FRET) detection of protein interaction in living cells is commonly measured following the expression of interacting proteins genetically fused to the cyan (CFP) and yellow (YFP) derivatives of the Aequorea victoria fluorescent protein (FP). These FPs can dimerize at mM concentrations, which may introduce artifacts into the measurement of interaction between proteins that are fused with the FPs. Here, FRET analysis of the interaction between estrogen receptors (alpha isoform, ERalpha) labeled with "wild-type" CFP and YFP is compared with that of ERalpha labeled with "monomeric" A206K mutants of CFP and YFP. The intracellular equilibrium dissociation constant for the hormone-induced ERalpha-ERalpha interaction is similar for ERalpha labeled with wild-type or monomeric FPs. However, the measurement of energy transfer measured for ERalpha-ERalpha interaction in each cell is less consistent with the monomeric FPs. Thus, dimerization of the FPs does not affect the kinetics of ERalpha-ERalpha interaction but, when brought close together via ERalpha-ERalpha interaction, FP dimerization modestly improves FRET measurement.