The Auditory Afferent Pathway as a Clinical Marker of Alzheimer's Disease.

Brain stem neural tracts and nuclei may be disturbed prior to observable neuronal atrophy in AD. In this perspective, we discuss the notion of functional deficits presenting prior to structural abnormalities in Alzheimer's disease (AD). Imaging of inferior colliculi using magnetic resonance spectroscopy (MRS) shows significant decrease in the neuronal markers, N acetyl aspartate/creatine ratio and increase in the glial marker myo-Inositol, in subjects with Mini-Mental State Examination scores greater than 24 and with no signs of atrophy in their MRI of the medial temporal lobe. Abnormalities in components of the auditory event-related potentials (ERPs) are described in cognitive impairment including AD. We observed a significant decrease in amplitude and increase in latency during the first 10 ms of auditory evoked potentials measured on electroencephalography (EEG) indicating slow auditory response of the brainstem. EEG spectral power recorded at the cortex is also associated with neural activity at the level of the inferior colliculi. We postulate that a functional examination of auditory afferent pathways, using non-invasive techniques, such as MRS, brain stem auditory evoked potentials (BAEPs) and ERPs may improve diagnostic accuracy of AD. Functional changes precede structural changes and it is important to further understand the relationship between biochemical and electrophysiological measures such as MRS, BAEPs and EEG.

Involvement of central sensory pathways in subjects with restless legs syndrome: A neurophysiological study.

In patients with restless legs syndrome (RLS) a motor cortical disinhibition has been reported in transcranial magnetic stimulation (TMS) studies, but the neuronal excitability in other cortical areas has been poorly explored. The aim of this study was the functional evaluation of thalamo-cortical circuits and inhibitory cortical responses in the sensory cortex in RLS. We assessed the high-frequency somatosensory evoked potentials (HF-SEP) in sixteen subjects suffering from RLS of different degrees of severity. In patients with severe or very severe RLS we found a significant desynchronization with amplitude reduction of both pre- and post-synaptic HF-SEP bursts, which suggest an impairment in the thalamo-cortical projections and in the cortical inhibitory interneurons activity, respectively. The assessment of the central sensory pathways by means of HF-SEP may shed light on the pathophysiological mechanisms of RLS.

Electrophysiological and anatomical characterization of synaptic remodeling in the mouse whisker thalamus.

In the central nervous system, developmental and pathophysiologic conditions cause a large-scale reorganization of functional connectivity of neural circuits. Here, by using a mouse model for peripheral sensory nerve injury, we present a protocol for combined electrophysiological and anatomical techniques to identify neural basis of synaptic remodeling in the mouse whisker thalamus. Our protocol provides comprehensive approaches to analyze both structural and functional components of synaptic remodeling. For complete details on the use and execution of this protocol, please refer to Ueta and Miyata, (2021).

Tonic GABAergic Inhibition Is Essential for Nerve Injury-Induced Afferent Remodeling in the Somatosensory Thalamus and Ectopic Sensations.

Peripheral nerve injury induces functional and structural remodeling of neural circuits along the somatosensory pathways, forming the basis for somatotopic reorganization and ectopic sensations, such as referred phantom pain. However, the mechanisms underlying that remodeling remain largely unknown. Whisker sensory nerve injury drives functional remodeling in the somatosensory thalamus: the number of afferent inputs to each thalamic neuron increases from one to many. Here, we report that extrasynaptic γ-aminobutyric acid-type A receptor (GABAAR)-mediated tonic inhibition is necessary for that remodeling. Extrasynaptic GABAAR currents were potentiated rapidly after nerve injury in advance of remodeling. Pharmacological activation of the thalamic extrasynaptic GABAARs in intact mice induced similar remodeling. Notably, conditional deletion of extrasynaptic GABAARs in the thalamus rescued both the injury-induced remodeling and the ectopic mechanical hypersensitivity. Together, our results reveal a molecular basis for injury-induced remodeling of neural circuits and may provide a new pharmacological target for referred phantom sensations after peripheral nerve injury.

Effects of electroacupuncture on stress-induced gastric dysrhythmia and mechanisms involving autonomic and central nervous systems in functional dyspepsia.

Electroacupuncture (EA) is widely used as an effective method to treat stress-related disorders. However, its mechanisms remain largely unknown. The aim of this study was to investigate the effects and mechanisms of EA on gastric slow wave (GSW) dysrhythmia and c-Fos expression in the nucleus of the solitary tract (NTS) induced by stress in a rodent model of functional dyspepsia (FD). Rats in the neonatal stage were treated using intragastric iodoacetamide. Eight weeks later, the rats were implanted with electrodes in the stomach for the measurement of GSW and electrodes into accupoints ST36 for EA. Autonomic functions were assessed by spectral analysis of heart rate variability. Rats were placed for 30 min in a cylindrical plastic tube for acute restraint stress. The involvement of a central afferent pathway was assessed by measuring c-Fos-immunoreactive cells in the NTS. 1) EA normalized restraint stress-induced impairment of GSW in FD rats. 2) EA significantly increased vagal activity (P = 0.002) and improved sympathovagal balance (P = 0.004) under stress in FD rats. 3) In FD rats under restraint stress, plasma norepinephrine concentration was increased substantially (P < 0.01), which was suppressed with EA. 4) The EA group showed increased c-Fos-positive cell counts in the NTS compared with the sham EA group (P < 0.05) in FD rats. Acute restraint stress induces gastric dysrhythmia in a rodent model of FD. EA at ST36 improves GSW under stress in FD rats mediated via the central and autonomic pathways, involving the NTS and vagal efferent pathway.

Gentle Perineal Skin Stimulation for Control of Nocturia.

One of the major causes of nocturia is overactive bladder (OAB). Somatic afferent nerve stimuli are used for treating OAB. However, clinical evidence for the efficacy of this treatment is insufficient due to the lack of appropriate control stimuli. Studies on anesthetized animals, which eliminate emotional factors and placebo effects, have demonstrated an influence of somatic stimuli on urinary bladder functions and elucidated the underlying mechanisms. In general, the effects of somatic stimuli are dependent on the modality, location, and physical characteristics of the stimulus. Recently we showed that gentle stimuli applied to the perineal skin using a soft elastomer roller inhibited micturition contractions to a greater extent than a roller with a hard surface. Studies aiming to elucidate the neural mechanisms of gentle stimulation-induced inhibition reported that 1-10 Hz discharges of low-threshold cutaneous mechanoreceptive Aß, Aδ, and C fibers evoked during stimulation with an elastomer roller inhibited the micturition reflex by activating the spinal cord opioid system, thereby reducing both ascending and descending transmission between bladder and pontine micturition center. The present review will provide a brief summary of (1) the effect of somatic electrical stimulation on the micturition reflex, (2) the effect of gentle mechanical skin stimulation on the micturition reflex, (3) the afferent, efferent, and central mechanisms underlying the effects of gentle stimulation, and (4) a translational clinical study demonstrating the efficacy of gentle skin stimuli for treating nocturia in the elderly with OAB by using the two roller types inducing distinct effects on rat micturition contractions. Anat Rec, 302:1824-1836, 2019. © 2019 American Association for Anatomy.

The vagus neurometabolic interface and clinical disease.

The nervous system both monitors and modulates body metabolism to maintain homoeostasis. In disease states such as obesity and diabetes, the neurometabolic interface is dysfunctional and contributes to clinical illness. The vagus nerve, in particular, with both sensory and motor fibres, provides an anatomical substrate for this interface. Its sensory fibres contain receptors for important circulating metabolic mediators, including leptin and cholecystokinin, and provide real-time information about these mediators to the central nervous system. In turn, efferent fibres within the vagus nerve participate in a brain-gut axis to regulate metabolism. In this review, we describe these vagus nerve-mediated metabolic pathways and recent clinical trials of vagus nerve stimulation for the management of obesity. These early studies suggest that neuromodulation approaches that employ electricity to tune neurometabolic circuits may represent a new tool in the clinical armamentarium directed against obesity.

Second-order spinal cord pathway contributes to cortical responses after long recoveries from dorsal column injury in squirrel monkeys.

Months after the occurrence of spinal cord dorsal column lesions (DCLs) at the cervical level, neural responses in the hand representation of somatosensory area 3b hand cortex recover, along with hand use. To examine whether the second-order spinal cord pathway contributes to this functional recovery, we injected cholera toxin subunit B (CTB) into the hand representation in the cuneate nucleus (Cu) to label the spinal cord neurons, and related results to cortical reactivation in four squirrel monkeys (Saimiri boliviensis) at least 7 months after DCL. In two monkeys with complete DCLs, few CTB-labeled neurons were present below the lesion, and few neurons in the affected hand region in area 3b responded to touch on the hand. In two other cases with large but incomplete DCLs, CTB-labeled neurons were abundant below the lesion, and the area 3b hand cortex responded well to tactile stimulation in a roughly somatotopic organization. The proportions of labeled neurons in the spinal cord hand region reflected the extent of cortical reactivation to the hand. Comparing monkeys with short and long recovery times suggests that the numbers of labeled neurons below the lesion increase with time following incomplete DCLs (<95%) but decrease with time after nearly complete DCLs (≥95%). Taken together, these results suggest that the second-order spinal cord pathway facilitates cortical reactivation, likely through the potentiation of persisting tactile inputs from the hand to the Cu over months of postlesion recovery.

Effects of action observation therapy and mirror therapy after stroke on rehabilitation outcomes and neural mechanisms by MEG: study protocol for a randomized controlled trial.

BACKGROUND: Loss of upper-extremity motor function is one of the most debilitating deficits following stroke. Two promising treatment approaches, action observation therapy (AOT) and mirror therapy (MT), aim to enhance motor learning and promote neural reorganization in patients through different afferent inputs and patterns of visual feedback. Both approaches involve different patterns of motor observation, imitation, and execution but share some similar neural bases of the mirror neuron system. AOT and MT used in stroke rehabilitation may confer differential benefits and neural activities that remain to be determined. This clinical trial aims to investigate and compare treatment effects and neural activity changes of AOT and MT with those of the control intervention in patients with subacute stroke. METHODS/DESIGN: An estimated total of 90 patients with subacute stroke will be recruited for this study. All participants will be randomly assigned to receive AOT, MT, or control intervention for a 3-week training period (15 sessions). Outcome measurements will be taken at baseline, immediately after treatment, and at the 3-month follow-up. For the magnetoencephalography (MEG) study, we anticipate that we will recruit 12 to 15 patients per group. The primary outcome will be the Fugl-Meyer Assessment score. Secondary outcomes will include the modified Rankin Scale, the Box and Block Test, the ABILHAND questionnaire, the Questionnaire Upon Mental Imagery, the Functional Independence Measure, activity monitors, the Stroke Impact Scale version 3.0, and MEG signals. DISCUSSION: This clinical trial will provide scientific evidence of treatment effects on motor, functional outcomes, and neural activity mechanisms after AOT and MT in patients with subacute stroke. Further application and use of AOT and MT may include telerehabilitation or home-based rehabilitation through web-based or video teaching. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02871700 . Registered on 1 August 2016.

Afferent Fiber Remodeling in the Somatosensory Thalamus of Mice as a Neural Basis of Somatotopic Reorganization in the Brain and Ectopic Mechanical Hypersensitivity after Peripheral Sensory Nerve Injury.

Plastic changes in the CNS in response to peripheral sensory nerve injury are a series of complex processes, ranging from local circuit remodeling to somatotopic reorganization. However, the link between circuit remodeling and somatotopic reorganization remains unclear. We have previously reported that transection of the primary whisker sensory nerve causes the abnormal rewiring of lemniscal fibers (sensory afferents) on a neuron in the mouse whisker sensory thalamus (V2 VPM). In the present study, using transgenic mice whose lemniscal fibers originate from the whisker sensory principle trigeminal nucleus (PrV2) are specifically labeled, we identified that the transection induced retraction of PrV2-originating lemniscal fibers and invasion of those not originating from PrV2 in the V2 VPM. This anatomical remodeling with somatotopic reorganization was highly correlated with the rewiring of lemniscal fibers. Origins of the non-PrV2-origin lemniscal fibers in the V2 VPM included the mandibular subregion of trigeminal nuclei and the dorsal column nuclei (DCNs), which normally represent body parts other than whiskers. The transection also resulted in ectopic receptive fields of V2 VPM neurons and extraterritorial pain behavior on the uninjured mandibular region of the face. The anatomical remodeling, emergence of ectopic receptive fields, and extraterritorial pain behavior all concomitantly developed within a week and lasted more than three months after the transection. Our findings, thus, indicate a strong linkage between these plastic changes after peripheral sensory nerve injury, which may provide a neural circuit basis underlying large-scale reorganization of somatotopic representation and abnormal ectopic sensations.

After-effects of peripheral neurostimulation on brain plasticity and ankle function in chronic stroke: The role of afferents recruited.

AIMS OF THE STUDY: This study tested the after-effects of neuromuscular electrical stimulation (NMES), repetitive peripheral magnetic stimulation (rPMS) and muscle tendon vibration (VIB) on brain plasticity and sensorimotor impairments in chronic stroke to investigate whether different results could depend on the nature of afferents recruited by each technique. MATERIALS AND METHODS: Fifteen people with chronic stroke participated in five sessions (one per week). Baseline measures were collected in session one, then, each participant received 4 randomly ordered interventions (NMES, rPMS, VIB and a 'control' intervention of exercises). Interventions were applied to the paretic ankle muscles and parameters of application were matched as closely as possible. Standardized clinical measures of the ankle function on the paretic side and transcranial magnetic stimulation (TMS) outcomes of both primary motor cortices (M1) were collected at pre- and post-application of each intervention. RESULTS: The ankle muscle strength was significantly improved by rPMS and VIB (P≤0.02). rPMS influenced M1 excitability (increase in the contralesional hemisphere, P=0.03) and inhibition (decrease in both hemispheres, P≤0.04). The group mean of a few clinical outcomes improved across sessions, i.e. independently of the order of interventions. Some TMS outcomes at baseline could predict the responsiveness to rPMS and VIB. CONCLUSION: This original study suggests that rPMS and VIB were efficient to drive M1 plasticity and sensorimotor improvements, likely via massive inflows of 'pure' proprioceptive information generated. Usefulness of some TMS outcomes to predict which intervention a patient could be more responsive to should be further tested in future studies.

Dysphagia Post Subcortical and Supratentorial Stroke.

BACKGROUND: Studies have recognized that the damage in the subcortical and supratentorial regions may affect voluntary and involuntary aspects of the swallowing function. The current study attempted to explore the dysphagia characteristics in patients with subcortical and supratentorial stroke. METHODS: Twelve post first or second subcortical and supratentorial stroke patients were included in the study. The location of the stroke was ascertained by computed tomography and magnetic resonance imaging. The characteristics of swallowing disorder were assessed by video fluoroscopic swallowing assessment/fiberoptic endoscopic evaluation of swallowing. The following main parameters were analyzed: oral transit time, pharyngeal delay time, presence of cricopharyngeal muscle achalasia (CMA), distance of laryngeal elevation, the amounts of vallecular residue and pyriform sinus residue (PSR), and the extent of pharyngeal contraction. RESULTS: Eighty-three percent of the 12 patients were found suffering from pharyngeal dysphagia, with 50% having 50%-100% PSRs, 50% having pharyngeal delay, and 41.6% cases demonstrating CMA. Simple regression analysis showed PSRs were most strongly associated with CMA. Pharyngeal delay in the study can be caused by infarcts of basal ganglia/thalamus, infarcts of sensory tract, infarcts of swallowing motor pathways in the centrum semiovale, or a combination of the three. CONCLUSION: Subcortical and supratentorial stroke may result in pharyngeal dysphagia such as PSR and pharyngeal delay. PSR was mainly caused by CMA.

Effects of passive heat stress on human somatosensory processing.

Herein, we investigated the effects of passive heat stress on human somatosensory processing recorded by somatosensory-evoked potentials (SEPs). Fifteen healthy subjects received a median nerve stimulation at the left wrist under two thermal conditions: Heat Stress and normothermic Time Control. The latencies and amplitudes of P14, N20, P25, N35, P45, and N60 at C4' and P14, N18, P22, and N30 at Fz were evaluated. Under the Heat Stress condition, SEPs were recorded at normothermic baseline (1st), early in heat stress (2nd), when esophageal temperature had increased by ~1.0°C (3rd) and ~2.0°C (4th), and after heat stress (5th). In the Time Control condition, SEPs were measured at the same time intervals as those in the Heat Stress condition. The peak latencies and amplitudes of SEPs did not change early in heat stress. However, the latencies of P14, N20, and N60 at C4' and P14, N18, and P22 at Fz were significantly shorter in the 4th session than in the 1st session. Furthermore, the peak amplitudes of P25 and N60 at C4', and P22 and N30 at Fz decreased with increases in body temperature. On the other hand, under the Time Control condition, no significant differences were observed in the amplitudes or latencies of any component of SEPs. These results suggested that the conduction velocity of the ascending somatosensory input was accelerated by increases in body temperature, and hyperthermia impaired the neural activity of cortical somatosensory processing.

Intracortical and Thalamocortical Connections of the Hand and Face Representations in Somatosensory Area 3b of Macaque Monkeys and Effects of Chronic Spinal Cord Injuries.

Brains of adult monkeys with chronic lesions of dorsal columns of spinal cord at cervical levels undergo large-scale reorganization. Reorganization results in expansion of intact chin inputs, which reactivate neurons in the deafferented hand representation in the primary somatosensory cortex (area 3b), ventroposterior nucleus of the thalamus and cuneate nucleus of the brainstem. A likely contributing mechanism for this large-scale plasticity is sprouting of axons across the hand-face border. Here we determined whether such sprouting takes place in area 3b. We first determined the extent of intrinsic corticocortical connectivity between the hand and the face representations in normal area 3b. Small amounts of neuroanatomical tracers were injected in these representations close to the electrophysiologically determined hand-face border. Locations of the labeled neurons were mapped with respect to the detailed electrophysiological somatotopic maps and histologically determined hand-face border revealed in sections of the flattened cortex stained for myelin. Results show that intracortical projections across the hand-face border are few. In monkeys with chronic unilateral lesions of the dorsal columns and expanded chin representation, connections across the hand-face border were not different compared with normal monkeys. Thalamocortical connections from the hand and face representations in the ventroposterior nucleus to area 3b also remained unaltered after injury. The results show that sprouting of intrinsic connections in area 3b or the thalamocortical inputs does not contribute to large-scale cortical plasticity. Significance statement: Long-term injuries to dorsal spinal cord in adult primates result in large-scale somatotopic reorganization due to which chin inputs expand into the deafferented hand region. Reorganization takes place in multiple cortical areas, and thalamic and medullary nuclei. To what extent this brain reorganization due to dorsal column injuries is related to axonal sprouting is not known. Here we show that reorganization of primary somatosensory area 3b is not accompanied with either an increase in intrinsic cortical connections between the hand and face representations, or any change in thalamocortical inputs to these areas. Axonal sprouting that causes reorganization likely takes place at subthalamic levels.

Sensory electrical stimulation for suppression of postural tremor in patients with essential tremor.

Essential tremor is an involuntary trembling of body limbs in people without tremor-related disease. In previous study, suppression of tremor by sensory electrical stimulation was confirmed on the index finger. This study investigates the effect of sensory stimulation on multiple segments and joints of the upper limb. It denotes the observation regarding the effect's continuity after halting the stimulation. 18 patients with essential tremor (8 men and 10 women) participated in this study. The task, "arms stretched forward", was performed and sensory electrical stimulation was applied on four muscles of the upper limb (Flexor Carpi Radialis, Extensor Carpi Radialis, Biceps Brachii, and Triceps Brachii) for 15 seconds. Three 3-D gyro sensors were used to measure the angular velocities of segments (finger, hand, and forearm) and joints (metacarpophalangeal and wrist joints) for three phases of pre-stimulation (Pre), during-stimulation (On), and 5 minute post-stimulation (P5). Three characteristic variables of root-mean-squared angular velocity, peak power, and peak power frequency were derived from the vector sum of the sensor signals. At On phase, RMS velocity was reduced from Pre in all segments and joints while peak power was reduced from Pre in all segments and joints except for forearm segment. Sensory stimulation showed no effect on peak power frequency. All variables at P5 were similar to those at On at all segments and joints. The decrease of peak power of the index finger was noted by 90% during stimulation from that of On phase, which was maintained even after 5 min. The results indicate that sensory stimulation may be an effective clinical method to treat the essential tremor.

Noninvasive neurostimulation in chronic stroke: a double-blind randomized sham-controlled testing of clinical and corticomotor effects.

BACKGROUND: Repetitive peripheral magnetic stimulation (RPMS) is a painless and noninvasive method to produce afferents via the depolarization of the peripheral nervous system. A few studies tested RPMS after-effects on cerebral plasticity and motor recovery in stroke individuals, but evidences remain limited. OBJECTIVES: This study aimed to explore whether RPMS could mediate improvements in corticomotor and clinical outcomes associated with ankle impairments in chronic stroke. METHODS: Eighteen subjects with chronic stroke were randomly allocated to RPMS or sham group and compared to 14 healthy subjects. Stimulation was applied over the paretic tibialis anterior (TA). Ankle impairments on the paretic side and ipsilesional TA cortical motor representation were tested clinically and by transcranial magnetic stimulation (TMS), respectively. RESULTS: In the RPMS group, ankle dorsiflexion mobility and maximal isometric strength increased and resistance to plantar flexor stretch decreased. The magnitude of change seemed to be related to cortical and corticospinal integrity. Sham stimulation yielded no effect. Changes in TMS outcome and their relationships with clinical improvements were limited. CONCLUSIONS: RPMS improved ankle impairments in chronic stroke likely by a dynamic influence of sensory inputs on synaptic plasticity. The neurophysiological mechanisms potentially underlying the clinical effects are unclear. More studies are warranted to test the spinal and hemispheric changes responsible for the clinical improvements with emphasis on circuits spared by the lesion.

Decreased face primary motor cortex (face-M1) excitability induced by noxious stimulation of the rat molar tooth pulp is dependent on the functional integrity of face-M1 astrocytes.

Acute inflammatory dental pain is a prevalent condition often associated with limited jaw movements. Mustard oil (MO, a small-fiber excitant/inflammatory irritant) application to the rat molar tooth pulp induces increased excitability (i.e., central sensitization) of trigeminal medullary dorsal horn (MDH) nociceptive neurons that can be modulated by MDH application of the astrocytic inhibitor methionine sulfoximine (MSO). The objectives of the study were to determine whether MO application to the rat right maxillary first molar tooth pulp affects left face-M1 excitability manifested as altered intracortical microstimulation thresholds for evoking electromyographic activity in the right anterior digastric (RAD, jaw-opening muscle), and whether MSO application to face-M1 can modulate this MO effect. Under Ketamine general anesthesia, Sprague-Dawley male rats had a microelectrode positioned at a low-threshold (≤30 µA) face-M1 site. Then MO (n = 16) or control solution (n = 16) was applied to the previously exposed tooth pulp, and RAD threshold was monitored for 15 min. MSO (0.1 mM, n = 8) or saline (n = 8) was then applied to the face-M1, and RAD thresholds were monitored every 15 min for 120 min. ANOVA followed by post hoc Bonferroni was used to analyze data (p < 0.05). Within 15 min of MO (but not control) pulp application, RAD thresholds increased significantly (p < 0.001) as compared to baseline. One hour following MSO (but not saline) application to the face-M1, RAD thresholds decreased significantly (p = 0.005) toward baseline. These novel findings suggest that acute inflammatory dental pain is associated with decreased face-M1 excitability that may be dependent on the functional integrity of face-M1 astrocytes and related to mechanisms underlying limited jaw movements in acute orofacial pain conditions.

Different cerebral responses to puncturing at ST36 among patients with functional dyspepsia and healthy subjects.

BACKGROUND: Little research has been done on the connection between functional status and acupuncture efficacy; however, functional status is a key factor in the study of acupuncture efficacy. Therefore, we have tried to compare functional dyspepsia (FD) patients with healthy subjects (HS) to determine the different cerebral responses elicited by acupuncture stimulation at Zusanli (ST36). PATIENTS AND METHODS: IN this study, 24 FD patients and 24 HS were given acupuncture stimulation at ST36 while being monitored by an fMRI scan. RESULTS: Compared with HS, FD patients showed an fMRI signal decrease in the right anterior cingulate cortex, right medial prefrontal cortex, right orbitofrontal cortex, left superior occipital gyrus, and right cuneus; but on the other hand, there was an fMRI signal increase in the right insula, right postcentral gyrus, and right supramarginal gyrus. CONCLUSION: Acupuncture stimulation at ST36 evoked pronounced changes, especially in the homeostatic afferent processing network of FD patients, compared to HS. We hypothesize that the cerebral responses elicited by acupuncture stimulation in certain diseases, such as FD are correlated to specific regions. The action of stimulating acupoints might be dynamic; the functional status is therefore an essential impact factor for cerebral responses to acupuncture stimulation.

The function of metabotropic glutamate receptors in thalamus and cortex.

Metabotropic glutamate receptors (mGluRs) are found throughout thalamus and cortex and are clearly important to circuit behavior in both structures, and so considering only participation of ionotropic glutamate receptors (e.g., [R,S]-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA] and N-methyl-d-aspartate receptors [NMDA] receptors) in glutamatergic processing would be an unfortunate oversimplification. These mGluRs are found both postsynaptically, on target cells of glutamatergic afferents, and presynaptically, on various synaptic terminals themselves, and when activated, they produce prolonged effects lasting at least hundreds of msec to several sec and perhaps longer. Two main types exist: activation of group I mGluRs causes postsynaptic depolarization, and group II, hyperpolarization. Both types are implicated in synaptic plasticity, both short term and long term. Their evident importance in functioning of thalamus and cortex makes it critical to develop a better understanding of how these receptors are normally activated, especially because they also seem implicated in a wide range of neurological and cognitive pathologies.

Peripheral afferent mechanisms underlying acupuncture inhibition of cocaine behavioral effects in rats.

Administration of cocaine increases locomotor activity by enhancing dopamine transmission. To explore the peripheral mechanisms underlying acupuncture treatment for drug addiction, we developed a novel mechanical acupuncture instrument (MAI) for objective mechanical stimulation. The aim of this study was to evaluate whether acupuncture inhibition of cocaine-induced locomotor activity is mediated through specific peripheral nerves, the afferents from superficial or deep tissues, or specific groups of nerve fibers. Mechanical stimulation of acupuncture point HT7 with MAI suppressed cocaine-induced locomotor activity in a stimulus time-dependent manner, which was blocked by severing the ulnar nerve or by local anesthesia. Suppression of cocaine-induced locomotor activity was elicited after HT7 stimulation at frequencies of either 50 (for Meissner corpuscles) or 200 (for Pacinian corpuscles) Hz and was not affected by block of C/Aδ-fibers in the ulnar nerve with resiniferatoxin, nor generated by direct stimulation of C/Aδ-fiber afferents with capsaicin. These findings suggest that HT7 inhibition of cocaine-induced locomotor activity is mediated by A-fiber activation of ulnar nerve that originates in superficial and deep tissue.