Unit Activity Responses Research Articles

Quantitative response of healthy muscle following the induction of capsaicin: an exploratory randomized controlled trial

BackgroundMyofascial pain syndrome (MPS) is a prevalent chronic pain disorder primarily characterized by myofascial trigger points (MTrPs). There is limited knowledge on the pathophysiology and mechanisms underlying MTrP and its development. Research has previously demonstrated the identification of MTrPs using ultrasound and vibration sonoelastography, although there is some contradictory evidence regarding if MTrPs present as hyper or hypoechoic regions. Electromyography (EMG) investigations of MTrP have demonstrated that MTrPs are usually located proximal to innervation zones where the peak surface EMG signals are obtained from. Central sensitization has been proposed as the primary mechanism underlying MTrP development. Central sensitization is associated with hyperexcitability of neuronal responses to normal or noxious stimuli. There is a need for a study that measures ultrasound image textural changes and motor unit activity responses in the muscle following sensitization. The purpose of this study is to determine whether sensitizing healthy muscle using capsaicin induces a regional change in image texture variables within the specific and surrounding muscles, as well as the motor unit frequency and amplitude changes that accompany them. This is an exploratory trial that aims to provide preliminary evidence on whether central sensitization is a direct cause of taut band and MTrP development.MethodsEthical approval was obtained from the University Health Network (UHN) Research Ethics Board. This proposed study is a single centered, factorial, randomized placebo-controlled trial with two independent variables, depth of capsaicin application and dose of capsaicin, for a total of six treatment arms and three control treatment groups.DiscussionThis will be the first study that assesses the B-mode ultrasound image texture of induced sensitized muscles and will provide more evidence on muscle motor unit activity and regional changes of central sensitization. Findings from this study may support one of few hypotheses proposed delineating the involvement of central sensitization in the development of trigger points.Trial registrationNational Institutes of Health ClinicalTrials.gov NCT03944889. Registered on May 07, 2019

Affective valence of neurons in the vicinity of the rat amygdala: Single unit activity in response to a conditioned behavior and vocal sound playback

We recorded single unit activity within and around the rat amygdala while rats were engaged in an operant task (which included both reward and aversive trials) and during playback of ultrasonic vocalizations (USVs) to determine if there existed neurons which responded to two different types of either positive contexts (i.e., water reward and positively associated 50kHz vocalizations) or negative contexts (i.e., white noise and negatively associated 22kHz vocalizations). Ultimately, we wanted to determine if these two contexts (operant condition task and vocal sounds) could be represented as either positive or negative in a single neuron. Neural activity in 90% of cells was modulated in response to one or more of those events. A small number of those cells showed neural responses to both the aversive operant trials and 22kHz USVs, but did not show responses to reward operant trials or 50kHz USVs, suggesting the activity of these neurons encodes for similar negative emotion in response to these two contexts. Some cells showed responses to either the reward trials or 50kHz USVs, but no cells showed responses to both, suggesting that these cells do not show a common response to events associated with positive emotion. This might mean that 50kHz vocal sounds and the operant rewards were segregated into two different categories within the neural representation at the level of the amygdala, even though it appeared that both events were associated with positive emotions in rats.

Early life stress causes FG-7142-induced corticolimbic dysfunction in adulthood

Maternal separation (MS) during the neonatal period enhances stress responsivity in adulthood. The medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA) are involved in coordinating various stress responses. Evidence indicates that MS reduces benzodiazepine and GABA A receptor expression in these regions, although their effects on neuronal function in the mPFC and the BLA remain unknown. The present study was conducted to assess the effects of MS on neuronal activity in the mPFC and BLA in response to the benzodiazepine receptor partial inverse agonist N-methyl-β-carboline-3-carboxamide (FG-7142). Rat pups were subjected to MS (360 min), brief handling (H; 15 min) or standard animal facility rearing (AFR) on postnatal days 2–14. In adult males, in vivo electrophysiology under isoflurane anesthesia was used to conduct acute recordings of extracellular unit activity in response to systemic FG-7142 administration. Animals subjected to H showed significantly increased basal mPFC activity compared to MS and AFR animals. There were no differences in basal BLA activity between the early rearing groups. In response to FG-7142, MS animals showed significantly attenuated mPFC activity compared to H animals and a nonsignificant trend towards attenuated mPFC activity compared to AFR animals. In contrast to mPFC, MS animals showed significantly potentiated FG-7142-induced activity in the BLA, compared to both H and AFR animals. These findings indicate that MS induces functionally relevant alterations in corticolimbic GABA A receptor signaling. Given that FG-7142 mimics several behavioral and physiological effects of stress, these results may also model stress-induced corticolimbic dysfunction caused by early life stress.

Insulin-induced hypoglycemia decreases single-unit activity of serotonergic medullary raphe neurons in freely moving cats: relationship to sympathetic and motor output.

Serotonergic single-unit activity during glucoregulatory challenges was studied in the nuclei raphe obscurus (NRO) and raphe pallidus (NRP) of freely moving cats. Systemic insulin administration (2-4 IU/kg, i.v.) suppressed neuronal activity by approximately 40% in direct relationship to blood glucose levels and in inverse relationship to plasma catecholamine levels. NRO and NRP serotonergic neurons displayed a temporary recovery in unit activity in response to i.v. glucose administration (500 mg/kg), which temporarily reversed insulin-induced hypoglycemia. The neuronal responses to insulin and subsequent glucose administration were also directly related to changes in integrated nuchal electromyographic activity. Serotonergic unit activity remained unchanged after glucose loading (500 mg/kg, i.v.), which produced a four-fold increase in blood glucose. Thus, medullary serotonergic neurons appear to be sensitive to reductions, but not increases, in blood glucose. The observed inverse relationship between unit activity and plasma catecholamines does not support a postulated sympathoexcitatory role for these neurons. Instead, the parallel changes in single-unit activity and integrated muscle activity support the hypothesis that the activity of medullary serotonergic neurons is linked to motor output. These neurons may modulate autonomic outflow, but only in relationship to their primary role in motor control. Finally, medullary serotonergic neurons may play a protective role in maintaining glucose homeostasis by disfacilitating the output of the somatomotor system, and hence diminishing muscle energy demands, when peripheral glucose availability is low.

Changes in the acoustically evoked activity in the inferior colliculus of the rat after functional ablation of the auditory cortex

The role of the cortico-tectal pathways in the processing of auditory signals was investigated by recording the click-evoked responses and extracellular multiple unit activity in the inferior colliculus (IC) after functional ablation of the auditory cortex (AC) by local intracortical application of a sodium channel blocker, tetrodotoxin (TTX). Click-evoked IC responses (IC-ER) and multiple unit activity in response to tone bursts were recorded with implanted electrodes in the IC of rats lightly anaesthetized with xylazine. Neural activity was recorded before and after the application of TTX into the ipsilateral auditory cortex (AC) through three implanted cannulas in a total dose of 30 ng. The functional status of the AC was monitored by recording click-evoked middle latency responses from a ball electrode implanted on the AC. During inactivation of the AC, IC-ER amplitudes were either increased (48 % of the cases), decreased (32 % of the cases) or not evidently changed (20 % of the cases). Corresponding effects were observed in the firing rate of IC neurons. Functional ablation of the AC also resulted in a significant prolongation of the latencies of individual waves of the IC-ER. However, the discharge pattern of the multiple unit responses, response thresholds and tuning were not altered during AC inactivation. IC neural activity recovered within several hours, and maximally during 2 days. The results reveal principles of the interaction of cortico-tectal pathways with IC neuronal activity.

Multiple representations of information in the primary auditory cortex of cats: I. Stability and change in slow components of unit activity after conditioning with a click conditioned stimulus

Recordings of activity were made from 647 single units of the A I cortex of awake cats to evaluate behavioral state-dependent changes in the population response to a 70-dB click. Averages of PST histograms of unit activity were used to assess the changes in response. This report focuses on slow components of the responses disclosed by averages employing bin widths of 16 ms. Responses were compared before and after a Pavlovian blink CR was produced by forward pairing of click conditioned stimuli (CSs) with USs. A backward-paired 70-dB hiss was presented as a discriminative stimulus. Studies were also done after backward pairing of the click CSs (backward conditioning) that produced weak sensitization instead of a conditioned response. There were four main findings. First, components of activity elicited 32–160 ms after presenting the hiss decreased significantly after conditioning and after backward conditioning. The decreases after conditioning represented the most pronounced changes in activity evoked by either clicks or hisses in this behavioral state. Second, baseline firing decreased after both conditioning and backward conditioning. The direction of baseline change was opposite that found in adjacent cortical regions and in A I cortex after operant conditioning employing an acoustic cue. Third, prior to conditioning, unit activity in response to the hiss declined before the sound of the hiss reached its peak or terminated. This decrease was thought to represent a habituatory adaptation of response to a prolonged acoustic stimulus. This type of habituation to a lengthy stimulus has been recognized, behaviorally, but has not been observed previously in the activity of units of the auditory receptive cortex. Fourth, the percentage of click responsive units did not change significantly after the click was used as a CS for conditioning, and despite the accompanying changes in baseline activity, the absolute levels of activity summed in the first 16 ms after click delivery remained stable across behavioral states in which the motor response to the click was altered profoundly. The onset of the conditioned motor response began 20 ms after the click, and was shown earlier to depend on rapid, potentiated transmission through the cochlear nucleus and motor cortex for its generation. Thus the stability of the response to the click in the primary auditory receptive cortex was unexpected. This led us to make further analyses of the data with 2- and 4-ms bin widths (see companion report) that eventually disclosed a potentiated response to the click. The findings show stability and change in the response to the click as a CS, depending on the band pass (bin width) used for analysis of spike activity. In the representation disclosed by low pass filtering in this study, the response was stable. This representation provided information suitable for identifying commonalties of the click signals across varying behavioral states. The representations of the click and hiss contained in the slow components of the population response in the A I cortex were uncorrelated with the selective potentiation of activity in motor cortex and behavioral performance in response to click as a CS after conditioning. Although changes in the activity evoked by hisses occurred after conditioning, the changes also occurred after backward conditioning when only small, sensitized behavioral responses to clicks and hisses were observed. Basic theoretical considerations about information transmission in complex neural networks plus clinical observations comparing derangements of linguistic and non-linguistic cortical functions in humans suggest that multiple representations of conditioned stimulus inputs may exist in local populations of cortical neurons. Together, our studies provide evidence for two different, concurrent representations of information about a click CS encoded in the spike activity of the A I cortex.

Hippocampal EEG and Unit Activity Responses to Modulation of Serotonergic Median Raphe Neurons in the Freely Behaving Rat

Hippocampal EEG, GABAergic interneurons, and principal cells were recorded simultaneously as rats foraged within one of three environments both before and after modulation of serotonergic inputs to the hippocampus. Median raphe microinjections of the 5-HT1a receptor agonist 8-OH-DPAT were made to produce inhibition of serotonergic neurons in this region. Such microinjections produced behavioral arousal and increases in the amplitude of hippocampal EEG theta. Consistent with the pattern of serotonergic innervation of the hippocampus, the GABAergic interneuron population was affected differentially by the microinjections. Principal cells were generally unaffected by the manipulation and maintained robust spatial firing correlates within the foraging environment. The results provide basic data on the relationship between serotonergic median raphe neurons and hippocampal activity in a behaving animal. The data suggest that behavioral responses to manipulation of the serotonergic system are mediated by brain regions other than the hippocampus or are mediated through changes in the activity of hippocampal interneurons.

Enhancement of parabrachial unit activity in response to sour taste after acquisition of a conditioned taste aversion.

Normal and brain-lesioned (amygdala, septal and nigral regions) rats exposed to fenitrothion (10 mg/kg) for 15 subsequent days showed elevated foot-shock fighting behaviour (septal and nigral lesioned rats). Treated animals failed to perform the rotorod test and showed decreased locomotor activity followed by convulsions. The brain-lesioned rats treated with 10 mg/kg fenitrothion showed a marked decrease in the level of norepinephrine (NE) and serotonin (5-HT).

2228 Enhancement of parabranchial unit activity in response to sour taste after acquisition of a conditioned taste aversion

Respiratory control differs dramatically across sleep stages. Indeed, along with rapid eye movements (REM), respiration was one of the first physiological variables shown to be modulated across sleep stages. The study of sleep stages, their physiological correlates, and neurobiological underpinnings present a challenge because of the fragility and unpredictability of individual stages, not to mention sleep itself. Although anesthesia has often substituted as a model for a unitary stage of slow-wave (non-REM) sleep, it is only recently that urethane anesthesia has been proposed to model the full spectrum of sleep given the presence of spontaneous brain state alternations and concurrent physiological correlates that appear remarkably similar to natural sleep. We describe this model, its parallels with natural sleep, and its power for studying modulation of respiration. Specifically, we report data on the EEG characteristics across brain states under urethane anesthesia, the dependence of brain alternations on neurotransmitter systems, and the observations on state dependent modulation of respiration.

Two distinct unit activity responses to morphine in the rostral ventromedial medulla of awake rats

Past research investigating the rostral ventromedial medulla (RVM) in anaesthetized animals has found two distinct classes of cells, ON and OFF, noted for their distinct responses to noxious stimuli and to morphine. However, only one class (ON) has been found in the awake animal paradigm. We report in this paper that we have found both the ON and OFF cell responses to morphine in the awake rat.

Evidence of subclinical brain influence in clinically complete spinal cord injury: discomplete SCI

Previous studies of the neurocontrol of movement in spinal cord injury (SCI) subjects revealed that even those without volitional movement may retain some degree of preservation of distal brain influence. We previously defined a discomplete lesion as one which is clinically complete but which is accompanied by neurophysiological evidence of residual brain influence on spinal cord function below the lesion. In order to document the nature and extent of such neurocontrol, we recorded surface EMGs from multiple muscle groups to study patterns of motor unit activity in response to tendon vibration, activation of muscles below the lesion by reinforcement maneuvers above the lesion and by voluntary suppression of plantar withdrawal reflexes. We analyzed data from this brain motor control assessment (BMCA) procedure in order to describe the frequency of occurence and characteristics of residual control in discomplete SCI subjects, comparing with findings in (clinically and neurophysiologically) complete and in (clinically and neurophysiologically) incomplete SCI subjects. From a group of 139 SCI subjects seen for management of spasticity, 88 had clinically complete lesions. Of these, 74 84%) were discomplete as defined by responses to the above maneuvers. The selection of management and intervention strategies, whether physiological, pharmacological, behavioral or surgical, should give consideration to the high likelihood that clinically complete subjects may be neurophysiologically incomplete.

Die Ortsfrequenzgrenze und das Auflösungsvermögen des visuellen Systems der Taube

The spatial contrast transfer function of the visual system of the pigeon was determined by recording from the optic tectum evoked potentials or extracellular unit activity in response to a pattern stimulus contrast transfer function, determined as a "response function", describes the relationship between the contrast in the pattern--which consisted of vertically oriented stripes of sinusoidally varying luminance--and the amplitude of the response at various spatial frequencies (c/deg). The transfer function yields an estimate of the high frequency limit, which in turn is a measure of visual resolving power. Action potentials were recorded extracellularly using glass microelectrodes; for evoked potentials, stainless steel electrodes were used. Recordings were made from the stratum griseum et fibrosum superficiale of the optic tectum. The highest spatial frequency detectable in a visual system is limited by various factors, including the diffraction of light at the pupil and the anatomical spacing of the photoreceptors. The pupil factor can be controlled in experiments in a suitable way. In this paper, the electrophysiologically determined high-frequency limit was compared with the theoretical resolution limit imposed by the photoreceptor mosaic. The experimental results show that the visual system of the pigeon has a high-frequency limit at a spatial frequency of 15.5 c/deg, corresponding to a visual acuity of 1.9 min of arc. The attempt to relate visual acuity in the pigeon to the anatomical spacing of the photoreceptors shows that the Nyquist frequency of the photoreceptor mosaic, the theoretical upper bound of the spatial resolution, agrees with measurement.

Neuronal activity of the locus ceruleus in awake Macaca arctoides

Neuronal activity in the locus ceruleus of awake, behaving stump-tailed monkeys increased consistently and vigorously after presentation of mildly aversive and threatening stimuli. These preliminary data increase the range of stimuli reported to elicit locus ceruleus activity in awake monkeys to include nonpainful threat signals and suggest that more studies are needed to be able to categorize locus ceruleus function from its unit activity responses.

Subcortical correlates of the auditory brain stem potentials in the monkey: bipolar EEG and multiple unit activity responses.

Bipolar EEG and multiple unit activity (MUA) responses correlated to the vertex auditory brain stem potentials (ABSP) were recorded in different brain stem and diencephalic primary auditory pathways and other anatomically related structures of large monkeys under barbiturate anesthesia. Bipolar EEG responses were recorded bilaterally to monaural stimulation and were formed by 3 or more of 6 consecutive components labeled A, B, C, D, E and F (peak latencies of 3.8, 4.2, 4.6, 5.0, 7.8 and 11.8 msec) correlated in latency with waves III, IV, V, VI, VII and SP3 of the ABSP, respectively. Component B was prominent and showed clearcut reverse polarity at the trapezoid body (TB) and superior olivary complex (SOC), while components C and F inverted and everted polarity at the mesencephalic reticular formation (MRF) and medial geniculate nucleus thalami (MG). Subcortical MUA peaks A, B, C, D and E time locked to the stimulus presentation correlated in latency to those of the bipolar EEG responses. In addition, a significant correlation was found between percentage amplitude of the subcortical EEG response components and MUA peaks in different structures contra- (r = 0.847) and ipsilateral (r = 0.973) to the stimulated ear. Although a single wave of the vertex ABSP correlated in latency with more than one response component in different subcortical loci, amplitude of component A was significantly larger (P less than or equal to 0.02) at TB ipsilateral, B at TB and SOC bilateral, and C and F at MRF, and D and E at MG contralateral to the stimulated ear.

Visual activity in the telencephalon of the painted turtle, Chrysemys picta

Multiple unit activity in response to visual stimulation was recorded in the following telencephalic areas of the painted turtle: lateral and medial divisions of the dorsal cortex, lateral and medial divisions of the dorsal ventricular ridge, and the striatum. The data confirm anatomical evidence for ascending visual input to the dorsal cortex, the lateral dorsal ventricular ridge and the striatum. The identification of a new visual zone in a medial division of the dorsal ventricular ridge suggests that turtles, and perhaps other reptiles, possessat least 3 visual pallial areas.

Responses of caudate neurons to clicks in chronic experiments on cats

Spontaneous and evoked unit activity in response to repeated application of clicks at a frequency of 0.3–2.0 Hz in the caudate nucleus was studied by an extracellular recording technique in chronic experiments on cats. Four types of spontaneous unit activity in the caudate nucleus were distinguished. Altogether 44% of neurons tested responded by changes in spontaneous activity to clicks. Five types of responses of caudate neurons to clicks were discovered: phasic excitation, phasic inhibition, tonic activation, tonic inhibition, and mixed tonic responses; the commonest type was tonic activation. During prolonged stimulation by clicks extinction of the phasic responses was not observed. Complete or partial extinction of tonic responses in the course of frequent repetition of stimulation was observed in 33% of responding neurons. The question of possible convergence of specific and nonspecific influences on caudate neurons is discussed.

Morphine-induced regional and dose-response differences in multiple-unit activity in rabbits

In each of 14 rabbits, EEG and multiple-unit activity were recorded from 14 brain areas which had been suggested in the literature as primary target sites of opiate action. Each rabbit received intraperitoneal injections of 5, 15, 0 (saline) and 25 mg/kg of morphine sulphate, in that order, with at least one week between injections. This sequence was repeated in a cross-over design to permit testing for tolerance. Experiments were performed with rabbits induced into the Immobility Reflex to produce a relatively stable artifact-free electrographic activity with minimal influence from behavioral feedback and other variables. EEG recordings disclosed a dose-related decrease in the incidence of theta rhythm; no evidence for tolerance development was evident. Subjective evaluation of tracings from all areas did not disclose any drug-related regional differences. Quantitative analysis of multiple unit activity revealed only a mild positive correlation between percent time theta and change in multiple unit activity (only for a few brain areas and usually at the highest dose). An unexpected, comparatively mild change in multiple unit activity in the caudate nucleus and the periaqueductal grey may have resulted from the special features of this experimental design: the focus on the immediate post-injection period and on spontaneous, rather than evoked, electrographic activity. Results in certain other areas supported the hypothesis of differential responsiveness to morphine, both in terms of brain areas affected and response latency. Those brain areas where multiple unit activity responses best fit our operational definition of target sites were the cingulate cortex and hippocampus, and perhaps to a lesser extent, the anterior and medial thalamic nuclei, brain stem reticular formation, cerebral cortex, fimbria/fornix, septum, and substantia nigra. We conclude that multiple unit activity is a sensitive index of opiate effect and that this approach is an appropriate in vivo method to identify and characterize primary sites of opiate action.

Spontaneous and evoked hypothalamic unit activity in kittens during development.

Spontaneous and evoked hypothalamic unit activity in response to sensory stimuli was studied in acute experiments on anesthetized kittens. After the second day of postnatal development, spontaneous unit activity can be recorded in the posterior hypothalamus. Evoked responses to sciatic nerve stimulation were recorded on the fourth to fifth day after birth. In the early stages of development phasic and tonic types of unit responses are present in the hypothalamus, with some predominance of phasic. At the end of the third week responses of hypothalamic neurons in kittens have still not reached their definitive formation.

Convergence of autonomic, somatic, and vestibular afferent impulses on single units of the medullary vasomotor center of the cat

Responses of vasomotor neurons of the cat medulla to electrical stimulation of the depressor nerve and of mixed nerves of the limbs and to adequate stimulation of the vestibular apparatus were investigated. Evoked unit activity was demonstrated as groups of action potentials followed by inhibition of spontaneous activity. Three types of unit responses to stimulation of the depressor nerve and somatic afferent fibers and changes in unit activity in response to vestibular stimulation are described. The features distinguishing the convergence of afferent impulses on vasomotor neurons are discussed.

Septal unit activity in response to alterations in blood volume and osmotic pressure

Activity of single septal units was recorded in rats anesthetized with Dial-urethane. Under ad lib food and water conditions, medial septal units discharged faster and had faster rise times than lateral septal cells. Hydration states were manipulated such that blood volume and osmotic pressure were changed both separately and together. Septal cells often responded both to volemic and to osmotic stimuli. Firing rates were usually faster during and after dehydrating stimuli than hydrating stimuli. Cells in ad lib rats discharged faster than cells in rats anesthetized either immediately before or immediately after the 0.5 hr drink period of a 23.5 hr water deprivation schedule.