Double-pulse Stimulation Research Articles

Latent toxoplasmosis impairs learning and memory yet strengthens short-term and long-term hippocampal synaptic plasticity at perforant pathway-dentate gyrus, and Schaffer collatterals-CA1 synapses

Investigating long-term potentiation (LTP) in disease models provides essential mechanistic insight into synaptic dysfunction and relevant behavioral changes in many neuropsychiatric and neurological diseases. Toxoplasma (T) gondii is an intracellular parasite causing bizarre changes in host’s mind including losing inherent fear of life-threatening situations. We examined hippocampal-dependent behavior as well as in vivo short- and long-term synaptic plasticity (STP and LTP) in rats with latent toxoplasmosis. Rats were infected by T. gondii cysts. Existence of REP-529 genomic sequence of the parasite in the brain was detected by RT-qPCR. Four and eight weeks after infection, spatial, and inhibitory memories of rats were assessed by Morris water maze and shuttle box tests, respectively. Eight weeks after infection, STP was assessed in dentate gyrus (DG) and CA1 by double pulse stimulation of perforant pathway and Shaffer collaterals, respectively. High frequency stimulation (HFS) was applied to induce LTP in entorhinal cortex-DG (400 Hz), and CA3-CA1 (200 Hz) synapses. T. gondii infection retarded spatial learning and memory performance at eight weeks post-infection period, whereas inhibitory memory was not changed. Unlike uninfected rats that normally showed paired-pulse depression, the infected rats developed paired-pulse facilitation, indicating an inhibitory synaptic network disruption. T. gondii-infected rats displayed strengthened LTP of both CA1-pyramidal and DG-granule cell population spikes. These data indicate that T. gondii disrupts inhibition/excitation balance and causes bizarre changes to the post-synaptic neuronal excitability, which may ultimately contribute to the abnormal behavior of the infected host.

Glutamate dynamics in the dorsolateral striatum of rats with goal-directed and habitual cocaine-seeking behavior.

The shift from drug abuse to addiction is considered to arise from the transition between goal-directed and habitual control over drug behavior. Habitual responding for appetitive and skill-based behaviors is mediated by potentiated glutamate signaling in the dorsolateral striatum (DLS), but the state of the DLS glutamate system in the context of habitual drug-behavior remains undefined. Evidence from the nucleus accumbens of cocaine-experienced rats suggests that decreased transporter-mediated glutamate clearance and enhanced synaptic glutamate release contribute to the potentiated glutamate signaling that underlies the enduring vulnerability to relapse. Preliminary evidence from the dorsal striatum of cocaine-experienced rats suggests that this region exhibits similar alterations to glutamate clearance and release, but it is not known whether these glutamate dynamics are associated with goal-directed or habitual control over cocaine-seeking behavior. Therefore, we trained rats to self-administer cocaine in a chained cocaine-seeking and -taking paradigm, which yielded goal-directed, intermediate, and habitual cocaine-seeking rats. We then assessed glutamate clearance and release dynamics in the DLS of these rats using two different methods: synaptic transporter current (STC) recordings of patch-clamped astrocytes and the intensity-based glutamate sensing fluorescent reporter (iGluSnFr). While we observed a decreased rate of glutamate clearance in STCs evoked with single-pulse stimulation in cocaine-experienced rats, we did not observe any cocaine-induced differences in glutamate clearance rates from STCs evoked with high frequency stimulation (HFS) or iGluSnFr responses evoked with either double-pulse stimulation or HFS. Furthermore, GLT-1 protein expression in the DLS was unchanged in cocaine-experienced rats, regardless of their mode of control over cocaine-seeking behavior. Lastly, there were no differences in metrics of glutamate release between cocaine-experienced rats and yoked-saline controls in either assay. Together, these results suggest that glutamate clearance and release dynamics in the DLS are largely unaltered by a history of cocaine self-administration on this established cocaine seeking-taking paradigm, regardless of whether the control over the cocaine seeking behavior was habitual or goal directed.

Motor point stimulation induces more robust F-waves than peripheral nerve stimulation.

The F-wave is a motor response induced by electrical stimulation of peripheral nerves via the antidromic firing of motor nerves, which reflects the motoneuron excitability. To induce F-waves, transcutaneous peripheral nerve stimulation (PNS) is used, which activates nerve branches via transcutaneous electrodes over the nerve branches. An alternative method to activate peripheral nerves, that is, motor point stimulation (MPS), which delivers electrical stimulation over the muscle belly, has not been used to induce F-waves. In our previous studies, we observed that MPS induced F-wave-like responses, that is, motor responses at the latency of F-waves at a supramaximal stimulation. Here, we further investigated the F-wave-like responses induced by MPS in comparison with PNS in the soleus muscle. Thirteen individuals participated in this study. We applied MPS and PNS on the participant's left soleus muscle. Using a monopolar double-pulse stimulation, the amplitude of the second H-reflex induced by PNS decreased, whereas the amplitude of the motor response at the F-wave latency induced by MPS did not decrease. These results suggest that the motor response at the F-wave latency induced by MPS was not an H-reflex but an F-wave. We also found that the F-wave induced by MPS had a greater amplitude and higher persistence and caused less pain when compared with the F-waves induced using PNS. We conclude that MPS evokes antidromic firing inducing F-waves more consistently compared with PNS.

Lentiviral Expression of Rabies Virus Glycoprotein in the Rat Hippocampus Strengthens Synaptic Plasticity.

Rabies virus (RABV) is a neurotropic virus exclusively infecting neurons in the central nervous system. RABV encodes five proteins. Among them, the viral glycoprotein (RVG) plays a key role in viral entry into neurons and rabies pathogenesis. It was shown that the nature of the C-terminus of the RABV G protein, which possesses a PDZ-binding motif (PBM), modulates the virulence of the RABV strain. The neuronal protein partners recruited by this PBM may alter host cell function. This study was conducted to investigate the effect of RVG on synaptic function in the hippocampal dentate gyrus (DG) of rat. Two μl (108T.U./ml) of the lentiviral vector containing RVG gene was injected into the DG of rat hippocampus. After 2weeks, the rat's brain was cross-sectioned and RVG-expressing cells were detected by fluorescent microscopy. Hippocampal synaptic activity of the infected rats was then examined by recording the local field potentials from DG after stimulation of the perforant pathway. Short-term synaptic plasticity was also assessed by double pulse stimulation. Expression of RVG in DG increased long-term potentiation population spikes (LTP-PS), whereas no facilitation of LTP-PS was found in neurons expressing δRVG (deleted PBM). Furthermore, RVG and δRVG strengthened paired-pulse facilitation. Heterosynaptic long-term depression (LTD) in the DG was significantly blocked in RVG-expressing group compared to the control group. This blockade was dependent to PBM motif as rats expressing δRVG in the DG-expressed LTD comparable to the RVG group. Our data demonstrate that RVG expression facilitates both short- and long-term synaptic plasticity in the DG indicating that it may involve both pre- and postsynaptic mechanisms to alter synaptic function. Further studies are needed to elucidate the underlying mechanisms.

Mapping of the Spinal Sensorimotor Network by Transvertebral and Transcutaneous Spinal Cord Stimulation.

Transcutaneous stimulation is a neuromodulation method that is efficiently used for recovery after spinal cord injury and other disorders that are accompanied by motor and sensory deficits. Multiple aspects of transcutaneous stimulation optimization still require testing in animal experiments including the use of pharmacological agents, spinal lesions, cell recording, etc. This need initially motivated us to develop a new approach of transvertebral spinal cord stimulation (SCS) and to test its feasibility in acute and chronic experiments on rats. The aims of the current work were to study the selectivity of muscle activation over the lower thoracic and lumbosacral spinal cord when the stimulating electrode was located intravertebrally and to compare its effectiveness to that of the clinically used transcutaneous stimulation. In decerebrated rats, electromyographic activity was recorded in the muscles of the back (m. longissimus dorsi), tail (m. abductor caudae dorsalis), and hindlimb (mm. iliacus, adductor magnus, vastus lateralis, semitendinosus, tibialis anterior, gastrocnemius medialis, soleus, and flexor hallucis longus) during SCS with an electrode placed alternately in one of the spinous processes of the VT12–VS1 vertebrae. The recruitment curves for motor and sensory components of the evoked potentials (separated from each other by means of double-pulse stimulation) were plotted for each muscle; their slopes characterized the effectiveness of the muscle activation. The electrophysiological mapping demonstrated that transvertebral SCS has specific effects to the rostrocaudally distributed sensorimotor network of the lower thoracic and lumbosacral cord, mainly by stimulation of the roots that carry the sensory and motor spinal pathways. These effects were compared in the same animals when mapping was performed by transcutaneous stimulation, and similar distribution of muscle activity and underlying neuroanatomical mechanisms were found. The experiments on chronic rats validated the feasibility of the proposed stimulation approach of transvertebral SCS for further studies.

Rate pitch discrimination in cochlear implant users with the use of double pulses and different interpulse intervals

The rate pitch discrimination ability of cochlear implant (CI) users is poor compared to normal-hearing (NH) listeners. At low pulse rates, the just noticeable difference (JND) is on average 20% of the base rate, while NH listeners can discriminate small frequency differences of 0.2% at 1 kHz. Recent investigations suggest that double pulses with short interpulse intervals (IPIs) may have a beneficial effect on rate pitch discrimination in CI users. In a first experiment psychophysical tests were carried out to establish whether rate pitch in CI users could be improved by applying double pulses with equal amplitude and short IPIs. Pulse trains with base rates of 200 and 400 pps, composed of either single pulses or double pulses with IPIs of 15, 50, and 150 μs were presented. In a second experiment pairwise comparisons were carried out between pitch of a pulse train composed of alternating double and single pulses with pitch of pulse trains composed of single pulses. The alternating pulse train had a base rate of 400 pps, the pulse trains with solely single pulses had base rates of 200, 300, and 400 pps. The loudness and pitch perception of the different stimulus types were evaluated and compared. A significant loudness difference was found between single and double pulses for both pulse rates. The JND for pitch discrimination between double-pulse IPIs had a high inter-subject variability, and no significant group effect was found. No subject reported a pitch change between double pulse and single pulse stimulation. In contrast, most of the subjects recognized a change in pitch between single-pulse trains and pulse trains with alternating double and single pulses. The latter was lower in pitch than the single-pulse train stimulation. To conclude, using (equal amplitude) double pulses instead of single pulses in a pulse train does not effect pitch perception. Instead, loudness differs between double pulses and single pulses with the same amplitude.

Repeatability of spinal reflexes of lower limb muscles evoked by transcutaneous spinal cord stimulation.

Transcutaneous electrical stimulation is a relatively new technique to evoke spinal reflexes in lower limb muscles. The advantage of this technique is that the spinal reflex responses can be obtained from multiple lower limb muscles simultaneously. However, repeatability of spinal reflexes evoked by transcutaneous spinal cord stimulation between days has not been evaluated. We aimed to examine repeatability of recruitment properties of the spinal reflexes evoked by transcutaneous spinal cord stimulation. Recruitment curves of the spinal reflexes evoked by transcutaneous spinal cord stimulation of 8 lower limb muscles (i.e., foot, lower leg, and thigh muscles) of 20 males were measured on two consecutive days. To confirm that responses were caused by activation of the sensory fiber, a double-pulse stimulation with 50 ms inter-pulse interval was delivered. Peak-to-peak amplitude of the first response was calculated for each muscle when no response was observed in the second response owing to post-activation depression. For comparison with the spinal reflexes evoked by transcutaneous spinal cord stimulation, the recruitment curves of the H-reflex amplitude of the soleus of 9 males were measured. Threshold intensity and maximal slope of the recruitment curves were calculated, and inter-day repeatability of the properties was quantified using intraclass correlation coefficients. For the spinal reflexes evoked by transcutaneous spinal cord stimulation, the intraclass correlation coefficient values of threshold intensity and maximal slope for each muscle ranged from 0.487 to 0.874 and from 0.471 to 0.964, respectively. Regarding the soleus H-reflex, the intraclass correlation coefficients of threshold intensity and maximal slope were 0.936 and 0.751, respectively. The present data showed that repeatability of the recruitment properties of the spinal reflexes evoked by transcutaneous spinal cord stimulation in the lower limb was moderate to high. Measurement of the spinal reflexes evoked by transcutaneous spinal cord stimulation would be useful for longitudinal neurophysiological studies.

Self-Reported Fatigue After Mild Traumatic Brain Injury Is Not Associated With Performance Fatigability During a Sustained Maximal Contraction.

Patients with mild traumatic brain injury (mTBI) are frequently affected by fatigue. However, hardly any data is available on the fatigability of the motor system. We evaluated fatigue using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS) questionnaires in 20 participants with mTBI (>3 months post injury; 8 females) and 20 age- and sex matched controls. Furthermore, index finger abduction force and electromyography of the first dorsal interosseous muscle of the right hand were measured during brief and sustained maximal voluntary contractions (MVC). Double pulse stimulation (100 Hz) was applied to the ulnar nerve to evoke doublet-forces before and after the sustained contraction. Seven superimposed twitches were evoked during the sustained MVC to quantify voluntary muscle activation. mTBI participants reported higher FSS scores (mTBI: 5.2 ± 0.8 SD vs. control: 2.8 ± 0.8 SD; P < 0.01). During the sustained MVC, force declined to similar levels in mTBI (30.0 ± 9.9% MVC) and control participants (32.7 ± 9.8% MVC, P = 0.37). The decline in doublet-forces after the sustained MVC (mTBI: to 37.2 ± 12.1 vs. control: to 41.4 ± 14.0% reference doublet, P = 0.32) and the superimposed twitches evoked during the sustained MVC (mTBI: median 9.3, range: 2.2–32.9 vs. control: median 10.3, range: 1.9–31.0% doubletpre, P = 0.34) also did not differ between groups. Force decline was associated with decline in doublet-force (R2 = 0.50, P < 0.01) for both groups. Including a measure of voluntary muscle activation resulted in more explained variance for mTBI participants only. No associations between self-reported fatigue and force decline or voluntary muscle activation were found in mTBI participants. However, the physical subdomain of the MFIS was associated with the decline in doublet-force after the sustained MVC (R2 = 0.23, P = 0.04). These results indicate that after mTBI, increased levels of self-reported physical fatigue reflected increased fatigability due to changes in peripheral muscle properties, but not force decline or muscle activation. Additionally, muscle activation was more important to explain the decline in voluntary force (performance fatigability) after mTBI than in control participants.

Age- and Sex-Related Differences in Motor Performance During Sustained Maximal Voluntary Contraction of the First Dorsal Interosseous.

Age and sex affect the neuromuscular system including performance fatigability. Data on performance fatigability and underlying mechanisms in hand muscles are scarce. Therefore, we determined the effects of age and sex on force decline, and the mechanisms contributing to force decline, during a sustained isometric maximal voluntary contraction (MVC) with the index finger abductor (first dorsal interosseous, FDI). Subjects (n = 51, age range: 19–77 years, 25 females) performed brief and a 2-min sustained MVC with the right FDI. Abduction force and root mean squared electromyographic activity (rms-EMG) were recorded in both hands. Double-pulse stimulation was applied to the ulnar nerve during (superimposed twitch) and after (doublet-force) the brief and sustained MVCs. Compared to females, males were stronger (134%, p < 0.001) and exhibited a greater decline in voluntary (difference: 8%, p = 0.010) and evoked (doublet) force (difference: 12%, p = 0.010) during and after the sustained MVC. Age did not affect MVC, force decline and superimposed twitch. The ratio between the doublet- and MVC-force was greater in females (0.33, p = 0.007) and in older (0.38, p = 0.06) individuals than in males (0.30) and younger (0.30) individuals; after the sustained MVC this ratio increased with age and the increase was larger for females compared to males (p = 0.04). The inadvertent contralateral, left force and rms-EMG activity increased over time (2.7–13.6% MVC and 5.4–17.7% MVC, respectively). Males had higher contralateral forces than females (p = 0.012) and contralateral force was higher at the start of the contralateral contraction in older compared with young subjects (difference: 29%, p = 0.008). In conclusion, our results suggest that the observed sex-differences in performance fatigability were mainly due to differences in peripheral muscle properties. Yet the reduced amount of contralateral activity and the larger difference in evoked versus voluntary force in female subjects indicate that sex-differences in voluntary activation should not be overlooked. These data obtained in neurological healthy adults provides a framework and help the interpretation and referencing of neurophysiological measures in patients suffering from neuromuscular diseases, who often present with symptoms of performance fatigability.

Effects of anode position on the responses elicited by transcutaneous spinal cord stimulation.

The purpose of this study was to investigate the effect of anode position on the spinal reflex responses evoked by transcutaneous spinal cord stimulation. Healthy males participated in two experiments. In Experiment 1 (Exp. 1, n = 3), we investigated the effect of anode position on the spinal reflex responses in multiple lower-limb muscles. Experiment 2 (Exp. 2, n = 8) focused on the effect of anode position on the spinal reflex response in the vastus medialis (VM) muscle. In each experiment, electromyographic signals were recorded in the right leg muscle(s). The cathode was placed over the area between the spinous processes of the L1 and L2 vertebrae. The anode was placed over (1) the abdomen (ABD), (2) the ipsilateral (right) anterior superior iliac spine (iASIS), or (3) the contralateral (left) anterior superior iliac spine (cASIS). A double pulse stimulation test was conducted to confirm that the response was due to activation of sensory fibers (i.e. spinal reflex). The results showed that the anode position was critical for inducing the spinal reflex in the VM (Exp. 1). The ratio of second to first responses was smaller when the anode was placed over the ABD or cASIS than when the anode was placed over the iASIS (Exp. 2). In addition, the onset latency of the first response was longer when the anode was placed over the ABD or cASIS than when the anode was placed over the iASIS (Exp. 2). These results showed that the anode should be placed over the ABD or cASIS to effectively elicit spinal reflexes in lower-limb muscles.

Activation Of Knee Extensor Muscles During Rapid Force Development In Men And Women

Adequacy of activation during rapid voluntary contractions is limited in young and old adults and can be shown by comparing the voluntary rate of force development (RFD) and electrically evoked RFD. Nonetheless, it is unknown whether the activation of rapid voluntary contractions differs between young men and women. PURPOSE: The purpose of this study was to compare the maximal RFD of young men and women during electrically evoked isometric contractions and rapid voluntary contractions with the knee extensor muscles across a range of torques. METHODS: Eight young adults (18-26 years; 4 men, 4 women) consented to sets of single and double pulse (10 ms interval) stimulations of the femoral nerve at maximal intensities followed by rapid voluntary isometric knee extensions at target torques matched to the electrically evoked torques. For the rapid voluntary isometric contractions, subjects were instructed to kick as fast as possible rather than as accurately as possible. Voluntary target torques ranged between 10-40% of maximal voluntary contraction (MVC) and were set to match the electrically evoked torques. Maximal RFD for each trial (voluntary and electrically evoked) was calculated as the peak values of the first derivative of the torque signal. RESULTS: Torques (between 10-40% MVC) were similar for the electrically evoked and voluntary contractions (F1,6=0.54, P=0.49) for both the men (25.0 ± 0.6 %MVC vs. 26.4 ± 0.7 %MVC) and women (26.0 ± 2.0 %MVC vs. 26.5 ± 2.7 %MVC). Although torques were similar, RFD from electrically evoked contractions in men (514.8 ± 30.4 % MVC.s−1) and women (475.1 ± 78.0 %MVC.s−1) was 36% greater than the voluntary contractions (men; 330.2 ± 18.8 vs. women; 305.9 ± 21.2 %MVC.s−1; F1.6 = 23.1, P = 0.003). The linear association between relative torque (%MVC) and electrically evoked RFD (R2 = 0.85, b = 0.92, P<0.001) was larger and steeper than the association with voluntary RFD (R2 = 0.72, b = 0.85, P<0.001) indicating that the difference in RFD between the electrically evoked and voluntary contractions increased at the higher forces. CONCLUSIONS: Young men and women had marked reductions in the ability to voluntarily generate isometric knee extension torque rapidly compared with electrically evoked contractions that were independent of the central nervous system. Supported by NIA R01 AG048262 to SKH

System Identification of Mechanomyogram Evoked by Double Pulse Stimulation

System Identification of Mechanomyogram Evoked by Double Pulse Stimulation

Evoked-potential recovery during double click stimulation in a beluga whale: implications for biosonar gain control.

Auditory evoked potentials (AEPs) were recorded in a beluga whale Delphinapterus leucas using a double-pulse stimulation paradigm, specifically measuring the recovery (release from masking) of the second (test) response as a function of delay after the first (conditioning) pulse at various levels of the conditioning and test stimuli. The conditioning/test stimulus level ratio influenced the recovery time (the higher the ratio, the longer the recovery). This interrelation was used to evaluate the intensity/time trade in release from forward masking. Trade was evaluated as 32.2 dB per time decade. Data were considered as simulating interactions between the transmitted pulse and echo during echolocation, assuming that a transmitted sonar pulse produces forward masking of the echo response. With increased target distance, the attenuation of the echo may be compensated by the release from masking. According to the model, the compensation results in substantial stabilization of the echo response even if the intensity/time trade of release from masking is not precisely equal to the rate of echo attenuation with distance.

Effects of deep brain stimulation of the nucleus basalis of Meynert in EEG resting-state oscillatory power and phase synchronization

s / Brain Stimulation 8 (2015) 360e377 376 pulse TMS over the right superior cerebellum (lobule 6) [3] and verified the necessity of the left superior (with visual and motor control) and inferior cerebellum during visual working memory with a double-pulse (1s interval) stimulation using fMRI-guided TMS [4]. In the current follow-up study, involvement of the right inferior cerebellum during visual working memory is further investigated. Methods: 9 healthy, right-handed young-adults performed 2 tasks: (1) Visual Memory TMS (VM-TMS) and (2) Verbal Memory TMS (VERM-TMS) while a double-pulse (1s interval) stimulation sequence was applied over the right inferior cerebellum (lobule 8A/ 7B) specific to VM activation during fMRI-guided (BrainSight Ver2) TMS (Magstim Rapid2 systemwith a 110mm double cone coil). Each task comprised of two runs of 18 stimulation (Stim) and 18 nonstimulation (non-Stim) trials per run (Fig. 1). Task order was counterbalanced across all subjects. Results: Paired t-tests showed, TMS administered to the right inferior cerebellum, decreased accuracy only in the VM-TMS task (t [8]1⁄44.64;p1⁄40.0017), but had no effects on RT or the VERM-TMS conditions (Fig. 2). Discussion: Our findings verified the contributions of the right inferior cerebellum during VM-TMS and possible topographic specificity for visual and verbal WM within this lobule. Kirschen et al. [5] showed the right lobule 8 to be activated specifically for auditory input and lobule 7B for visual processes during VERM. It is plausible that our lack of significant effect during VERM-TMS is explained by the TMS target to be within lobule 7B and not 8, hence disrupting the visual processes essential for VM but not VERM. Further investigations using VERM fMRIguided targets in the right inferior cerebellum are needed to ascertain this.

The P18 component of the median nerve SEP recorded from a posterior to anterior neck montage

ObjectiveTo investigate the P18 component in the posterior to anterior neck montage after median nerve stimulation. MethodsSomatosensory evoked potentials, through electrical wrist stimulation, were collected. In 12 subjects, the presence of the P18 component was evaluated in the posterior to anterior neck montage. In 10 subjects, the effects of simultaneous vibration of the hand were evaluated. In five subjects, responses after double-pulse stimulation (ISI 20ms) were evaluated. ResultsThe P18 component was identified in all subjects. Vibration reduced the amplitude of all components except the P18 and N18. Double-pulse stimulation reduced the amplitude of the P18 and the N18 components without significantly changing the amplitude of the other components. ConclusionsThe posterior to anterior neck montage allows for recording the P18 component. The amplitude reduction of all components during vibration, except N18 and P18, is interpreted as reflecting inhibitory activities at the cuneiform nucleus and at the segmental dorsal horn of the spinal cord, respectively. The reduction in the P18 component after double-pulse stimulation is compatible with previous observations on the positive component of cord dorsum potentials. SignificanceStudying this component may add to the knowledge of the function of the spinal cord in humans.

Multimodal Cross-Talk of Olfactory and Gustatory Information in the Endopiriform Nucleus in Rats

The endopiriform nucleus (EPN) is a large group of multipolar cells located in the depth of the piriform cortex (PC). Although many studies have suggested that the EPN plays a role in temporal lobe epilepsy, the normal function of the EPN remains to be elucidated. By using optical imaging of coronal brain slice preparations with voltage-sensitive dye, we found signal propagation from the PC or gustatory cortex (GC) to the EPN in normal medium. In our previous research, we failed to elicit a reliable signal reproducibly in the EPN by single stimulation either to the PC or GC. In our current research, we found that a double-pulse stimulation to either the PC or GC (interpulse interval: 20-100 ms) induced robust signal propagation to the EPN through excitation in the agranular division of the insular cortex (AI), with further extension to the claustrum. Finally, double site paired-pulse stimulation to the PC and GC also evoked excitation in the AI, claustrum, and EPN. These results suggest that the EPN has dual roles: 1) further processing of modality-specific olfactory and gustatory information from the PC and GC, respectively and 2) synergistic integration of PC-derived olfactory information and GC-derived gustatory information.

Rapid reversal of impaired inhibitory and excitatory transmission but not spine dysgenesis in a mouse model of mental retardation

Intellectual disability affects 2-3% of the population: those due to mutations of the X-chromosome are a major cause of moderate to severe cases (1.8/1000 males). Established theories ascribe the cellular aetiology of intellectual disability to malformations of dendritic spines. Recent work has identified changes in synaptic physiology in some experimental models. Here, we investigated the pathophysiology of a mouse model of intellectual disability using electrophysiological recordings combined with confocal imaging of dentate gyrus granule neurons. Lack of oligophrenin-1 resulted in reductions in dendritic tree complexity and mature dendritic spine density and in evoked and spontaneous EPSCs and IPSCs. In the case of inhibitory transmission, the physiological change was associated with a reduction in the readily releasable pool and vesicle recycling which impaired the efficiency of inhibitory synaptic transmission. Acute inhibition of the downstream signalling pathway of oligophrenin-1 fully reversed the functional changes in synaptic transmission but not the dendritic abnormalities. The impaired inhibitory (as well as excitatory) synaptic transmission at frequencies associated with cognitive function suggests a cellular mechanism for the intellectual disability, because cortical oscillations associated with cognition normally depend on inhibitory neurons firing on every cycle.

Electrophysiological and biochemical response in rats on intratracheal instillation of manganese

Abstract Chronic exposure to excess manganese via inhalation of metal fumes causes central nervous system damage. For modelling Mn aerosol inhalation, male Wistar rats were intratracheally instilled with MnCl2 solution (0.5 mg/kg b.w. MnCl2; n=12) 5 days a week for 5 weeks. At the end of the treatment, somatosensory cortical evoked potentials, elicited by double-pulse stimulation, were recorded from the animals in urethane anaesthesia. Body weight gain, organ weights, and Mn level in brain, lung and blood samples were also measured. In brain samples, gene expression level of MnSOD (Mn superoxide dismutase) was determined. The effect of Mn was mainly seen on the evoked potential amplitudes, and on the second:first ratio of these. Tissue Mn concentration was elevated in brain and lungs, but changed hardly in the blood. Relative weight of heart, thymus, lungs and brain was significantly altered. The level of MnSOD transcript in brain tissue decreased. The observed effects showed that Mn had access to the brain and that somatosensory cortical responses evoked by double-pulse stimulation might be suitable biomarkers of Mn intoxication.

Sympathetic activation by the cold pressor test does not increase the muscle force generation capacity

A positive inotropic action by the sympathetic nervous system on skeletal muscles has been observed and investigated in animal and in vitro studies. This action provided a theoretical basis for the putative ergogenic action of catecholamines and adrenergic agonists, although there is no clear evidence of this effect in humans. The aim of this study was to investigate the occurrence of inotropic effects associated to physiological sympathetic activation in healthy subjects. The muscle force capacity was investigated in the tibialis anterior (n = 9 subjects) and in the soleus (n = 9) muscles electrically stimulated with single pulses and double pulses with variable interspike interval (4-1,000 ms) and short pulse trains (frequency: 5-14 Hz) before, during, and after sympathetic activation by the cold pressor test (CPT). CPT significantly decreased by 10.4 ± 7.2 and 10.6 ± 4.4% the force produced by single and double pulse stimulation, respectively, and produced smaller decreases in the force obtained by train stimulation in the tibialis anterior, while no significant changes were observed in either type of contraction in the soleus muscle. CPT failed to induce any increase in the force capacity of the investigated muscles. The prevalent decrease in force evidenced in this study supports the concept that the weakening sympathetic action on type I fiber, already shown to occur in humans, prevails over the putative potentiating action.

Acute and chronic effect of manganese on the somatosensory system of rats investigated with double-pulse stimulation

Event Abstract Back to Event Acute and chronic effect of manganese on the somatosensory system of rats investigated with double-pulse stimulation Zsuzsanna Mate1, Andrea Szabo1* and András Papp1 1 Department of Public Health, University of Szeged , Hungary Manganese (Mn) is an essential ion for the body in small amounts, but toxic when overdosed. Long-term exposure (by welding, mining, certain pesticides, anti-knock agent MMT or contaminated drinking water) can lead to Mn accumulation in the central nervous system resulted in deterioration of GABAergic, dopaminergic and cholinergic system and impaired mitochondrial function finally causing Parkinson-like symptoms (manganism). The aim of this study was to look for an electrophysiological parameter suitable for early detection of altered neurological functions caused by Mn. Therefore a sensitive method proven by other mitochondrial toxins was used: evoked potentials induced by double-pulse stimulation of the whisker pad were recorded from primary somatosensory cortex of anaesthetized rats, applying different interstimulus intervals. Two time schemes were investigated: in acute experiment the animals were treated with 50 mg/ml MnCl2 intraperitoneally, while in the chronic treatment MnCl2 was administered to rats dissolved in their drinking water in 2.5 mg/ml concentration for 6 weeks. After treatments electrophysiological measurements were recorded. Amplitude and peak latency as parameters of evoked potentials was measured and second:first ratio (each parameters of the second evoked potential were divided by the corresponding parameters of the first) was calculated to see the fatigue. In the acute protocol the latency slightly lengthened and the amplitude of the potentials definitely increased. In the chronic scheme reduced amplitude and significantly decreased second:first latency ratio was seen. Amplitude can be a indicator of early-, and second:first latency ratio can be a marker parameter of delayed functional neurophysiological alterations caused by manganese. Conference: 12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009. Presentation Type: Poster Presentation Topic: Research on the cerebral cortex and related structures Citation: Mate Z, Szabo A and Papp A (2009). Acute and chronic effect of manganese on the somatosensory system of rats investigated with double-pulse stimulation. Front. Syst. Neurosci. Conference Abstract: 12th Meeting of the Hungarian Neuroscience Society. doi: 10.3389/conf.neuro.01.2009.04.212 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 09 Mar 2009; Published Online: 09 Mar 2009. * Correspondence: Andrea Szabo, Department of Public Health, University of Szeged, Szeged, Hungary, szaboa@puhe.szote.u-szeged.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Zsuzsanna Mate Andrea Szabo András Papp Google Zsuzsanna Mate Andrea Szabo András Papp Google Scholar Zsuzsanna Mate Andrea Szabo András Papp PubMed Zsuzsanna Mate Andrea Szabo András Papp Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.