Ventral Posterolateral Research Articles

Abstract 132: Chronic Optogenetic Stimulation of Thalamocortical Projections Promotes Axonal Rewiring and Accelerates Recovery of Function After Somatosensory Cortex Stroke

The majority of stroke survivors must cope with chronic disability of the limbs. Improved limb use is generally accompanied by neuroplasticity in surviving brain areas surrounding the stroke. Modulating this innate plasticity should promote further gains in recovery. One relatively unknown issue in stroke research concerns the role of the thalamus, the brain’s relay center for sensory information en route to the cortex. Unpublished data from our lab has shown that while peri-infarct thalamocortical axons are relatively resilient to the effects of ischemia, they are highly unstable and lose a significant number of synaptic boutons in the first few weeks after stroke. We now expand on this by hypothesizing that optogenetic stimulation of peri-infarct thalamocortical projections will promote axonal rewiring and improve recovery from somatosensory cortex stroke. Axons projecting from the VPL nucleus of the thalamus to primary forelimb somatosensory cortex were co-transfected with a fluorescently tagged adeno-associated virus that expressed channelrhodopsin-2 and mCherry. A chronic cranial window was then implanted to allow for longitudinal in vivo two-photon imaging of superficial thalamic axon terminals before and at various times after photothrombotic stroke. Optogenetic stimulation was driven by a blue LED (475 nm, 6-10mW/mm2) magnetically attached to the cranial window. Optical stimulation (5 ms pulses at 5 Hz every 5 seconds) or control procedures were initiated 3 days after stroke in freely moving mice for 1 hour/day, 5 days/week for 6 weeks after stroke. Behavioural performance on the Tape Removal Test and Ladder Walking Test were assessed once weekly throughout the entire recovery period. Preliminary data show that optogenetic stimulation of thalamocortical projections is associated with an attenuated period of thalamocortical bouton elimination, increased bouton formation and greater stability/persistence of newly formed boutons. Importantly, stimulated mice showed less severe forepaw deficits and faster recovery of sensorimotor function. These studies offer encouraging new insights into the application of optogenetic approaches for improving stroke recovery.

T-type calcium channel blocker Z944 restores cortical synchrony and thalamocortical connectivity in a rat model of neuropathic pain.

Oscillations are fundamental to communication between neuronal ensembles. We previously reported that pain in awake rats enhances synchrony in primary somatosensory cortex (S1) and attenuates coherence between S1 and ventral posterolateral (VPL) thalamus. Here, we asked whether similar changes occur in anesthetized rats and whether pain modulates phase-amplitude coupling between VPL and S1. We also hypothesized that the suppression of burst firing in VPL using Z944, a novel T-type calcium channel blocker, restores S1 synchrony and thalamocortical connectivity. Local field potentials were recorded from S1 and VPL in anesthetized rats 7 days after sciatic chronic constriction injury (CCI). In rats with CCI, low-frequency (4-12 Hz) synchrony in S1 was enhanced, whereas VPL-S1 coherence and theta-gamma phase-amplitude coupling were attenuated. Moreover, Granger causality showed decreased informational flow from VPL to S1. Systemic or intrathalamic delivery of Z944 to rats with CCI normalized these changes. Systemic Z944 also reversed thermal hyperalgesia and conditioned place preference. These data suggest that pain-induced cortical synchrony and thalamocortical disconnectivity are directly related to burst firing in VPL.

Hierarchical Distribution of the Tau Cytoskeletal Pathology in the Thalamus ofAlzheimer's Disease Patients.

In spite of considerable progress in neuropathological research on Alzheimer's disease (AD), knowledge regarding the exact pathoanatomical distribution of the tau cytoskeletal pathology in the thalamus of AD patients in the advanced Braak and Braak AD stages V or VI of the cortical cytoskeletal pathology is still fragmentary. Investigation of serial 100 μm-thick brain tissue sections through the thalamus of clinically diagnosed AD patients with Braak and Braak AD stage V or VI cytoskeletal pathologies immunostained with the anti-tau AT8 antibody, along with the affection of the extraterritorial reticular nucleus of the thalamus, reveals a consistent and severe tau immunoreactive cytoskeletal pathology in the limbic nuclei of the thalamus (e.g., paraventricular, anterodorsal and laterodorsal nuclei, limitans-suprageniculate complex). The thalamic nuclei integrated into the associative networks of the human brain (e.g., ventral anterior and mediodorsal nuclei) are only mildly affected, while its motor precerebellar (ventral lateral nucleus) and sensory nuclei (e.g., lateral and medial geniculate bodies, ventral posterior medial and lateral nuclei, parvocellular part of the ventral posterior medial nucleus) are more or less spared. The highly stereotypical and characteristic thalamic distribution pattern of the AD-related tau cytoskeletal pathology represents an anatomical mirror of the hierarchical topographic distribution of the cytoskeletal pathology in the interconnected regions of the cerebral cortex of AD patients. These pathoanatomical parallels support the pathophysiological concept of a transneuronal spread of the disease process of AD along anatomical pathways. The AD-related tau cytoskeletal pathology in the thalamus most likely contributes substantially to the neuropsychiatric disease symptoms (e.g., dementia), attention deficits, oculomotor dysfunctions, altered non-discriminative aspects of pain experience of AD patients, and the disruption of their waking and sleeping patterns.

Electroacupuncture Treatment Alleviates Central Poststroke Pain by Inhibiting Brain Neuronal Apoptosis and Aberrant Astrocyte Activation.

Electroacupuncture (EA) is reported to effectively relieve the central poststroke pain (CPSP). However, the underlying mechanism remains unclear. The present study investigated the detailed mechanisms of action of EA treatment at different frequencies for CPSP. A CPSP model was established with a single collagenase injection to the left ventral posterolateral nucleus of the thalamus. The EA-treated groups then received EA treatment at frequency of 2, 2/15, or 15 Hz for 30 min daily for five days. The pain-related behavioral responses, neuronal apoptosis, glial activation, and the expression of pain signal transmission-related factors (β-catenin, COX-2, and NK-1R) were assessed using behavioral tests, Nissl staining, TUNEL staining, and immunohistochemical staining, respectively. The low-frequency EA treatment significantly (1) reduced brain tissue damage and hematoma sizes and (2) inhibited neuronal apoptosis, thereby exerting abirritative effects. Meanwhile, the high-frequency EA treatment induced a greater inhibition of the aberrant astrocyte activation, accompanied by the downregulation of the expressions of COX-2, β-catenin, and subsequently NK-1R, thereby alleviating inflammation and producing strong analgesic effects. Together, these findings suggest that CPSP is closely related to pathological changes of the neocortex and hippocampus. EA treatments at different frequencies may exert abirritative effects by inhibiting brain neuronal apoptosis and aberrant astrocyte activation in the brain.

Functional characterization of a mouse model for central post-stroke pain

BackgroundStroke patients often suffer from a central neuropathic pain syndrome called central post-stroke pain. This syndrome is characterized by evoked pain hypersensitivity as well as spontaneous, on-going pain in the body area affected by the stroke. Clinical evidence strongly suggests a dysfunction in central pain pathways as an important pathophysiological factor in the development of central post-stroke pain, but the exact underlying mechanisms remain poorly understood. To elucidate the underlying pathophysiology of central post-stroke pain, we generated a mouse model that is based on a unilateral stereotactic lesion of the thalamic ventral posterolateral nucleus, which typically causes central post-stroke pain in humans.ResultsBehavioral analysis showed that the sensory changes in our model are comparable to the sensory abnormalities observed in patients suffering from central post-stroke pain. Surprisingly, pharmacological inhibition of spinal and peripheral key components of the pain system had no effect on the induction or maintenance of the evoked hypersensitivity observed in our model. In contrast, microinjection of lidocaine into the thalamic lesion completely reversed injury-induced hypersensitivity.ConclusionsThese results suggest that the evoked hypersensitivity observed in central post-stroke pain is causally linked to on-going neuronal activity in the lateral thalamus.

Rostral Agranular Insular Cortex Lesion with Motor Cortex Stimulation Enhances Pain Modulation Effect on Neuropathic Pain Model.

It is well known that the insular cortex is involved in the processing of painful input. The aim of this study was to evaluate the pain modulation role of the insular cortex during motor cortex stimulation (MCS). After inducing neuropathic pain (NP) rat models by the spared nerve injury method, we made a lesion on the rostral agranular insular cortex (RAIC) unilaterally and compared behaviorally determined pain threshold and latency in 2 groups: Group A (NP + MCS; n = 7) and Group B (NP + RAIC lesion + MCS; n = 7). Also, we simultaneously recorded neuronal activity (NP; n = 9) in the thalamus of the ventral posterolateral nucleus and RAIC to evaluate electrophysiological changes from MCS. The pain threshold and tolerance latency increased in Group A with “MCS on” and in Group B with or without “MCS on.” Moreover, its increase in Group B with “MCS on” was more than that of Group B without MCS or of Group A, suggesting that MCS and RAIC lesioning are involved in pain modulation. Compared with the “MCS off” condition, the “MCS on” induced significant threshold changes in an electrophysiological study. Our data suggest that the RAIC has its own pain modulation effect, which is influenced by MCS.

Intracortical connections are altered after long-standing deprivation of dorsal column inputs in the hand region of area 3b in squirrel monkeys.

A complete unilateral lesion of the dorsal column somatosensory pathway in the upper cervical spinal cord deactivates neurons in the hand region in contralateral somatosensory cortex (areas 3b and 1). Over weeks to months of recovery, parts of the hand region become reactivated by touch on the hand or face. To determine whether changes in cortical connections potentially contribute to this reactivation, we injected tracers into electrophysiologically identified locations in cortex of area 3b representing the reactivated hand and normally activated face in adult squirrel monkeys. Our results indicated that even when only partially reactivated, most of the expected connections of area 3b remained intact. These intact connections include the majority of intrinsic connections within area 3b; feedback connections from area 1, secondary somatosensory cortex (S2), parietal ventral area (PV), and other cortical areas; and thalamic inputs from the ventroposterior lateral nucleus (VPL). In addition, tracer injections in the reactivated hand region of area 3b labeled more neurons in the face and shoulder regions of area 3b than in normal monkeys, and injections in the face region of area 3b labeled more neurons in the hand region. Unexpectedly, the intrinsic connections within area 3b hand cortex were more widespread after incomplete dorsal column lesions (DCLs) than after a complete DCL. Although these additional connections were limited, these changes in connections may contribute to the reactivation process after injuries. J. Comp. Neurol. 524:1494-1526, 2016. © 2015 Wiley Periodicals, Inc.

Gating of tactile information through gamma band during passive arm movement in awake primates.

To make precise and prompt action in a dynamic environment, the sensorimotor system needs to integrate all related information. The inflow of somatosensory information to the cerebral cortex is regulated and mostly suppressed by movement, which is commonly referred to as sensory gating or gating. Sensory gating plays an important role in preventing redundant information from reaching the cortex, which should be considered when designing somatosensory neuroprosthetics. Gating can occur at several levels within the sensorimotor pathway, while the underlying mechanism is not yet fully understood. The average sensory evoked potential is commonly used to assess sensory information processing, however the assumption of a stereotyped response to each stimulus is still an open question. Event related spectral perturbation (ERSP), which is the power spectrum after time-frequency decomposition on single trial evoked potentials (total power), could overcome this limitation of averaging and provide additional information for understanding the underlying mechanism. To this aim, neural activities in primary somatosensory cortex (S1), primary motor cortex (M1), and ventral posterolateral (VPL) nucleus of thalamus were recorded simultaneously in two areas (S1 and M1 or S1 and VPL) during passive arm movement and rest in awake monkeys. Our results showed that neural activity at different recording areas demonstrated specific and unique response frequency characteristics. Tactile input induced early high frequency responses followed by low frequency oscillations within sensorimotor circuits, and passive movement suppressed these oscillations either in a phase-locked or non-phase-locked manner. Sensory gating by movement was non-phase-locked in M1, and complex in sensory areas. VPL showed gating of non-phase-locked at gamma band and mix of phase-locked and non-phase-locked at low frequency, while S1 showed gating of phase-locked and non-phase-locked at gamma band and an early phase-locked elevation followed by non-phase-locked gating at low frequency. Granger causality (GC) analysis showed bidirectional coupling between VPL and S1, while GC between M1 and S1 was not responsive to tactile input. Thus, these results suggest that tactile input is dominantly transmitted along the ascending direction from VPL to S1, and the sensory input is suppressed during movement through a bottom-up strategy within the gamma-band during passive movement.

Thalamic Stimulation in Awake Rats Induces Neurogenesis in the Hippocampal Formation.

Deep brain stimulation (DBS) provides clinical benefits for a variety of movement disorders and lately emerged as a potential treatment for cognitive and mood disorders. Modulation of adult hippocampal neurogenesis may play a role in mediating its effects. To investigate the effects of unilateral anteromedial thalamic nucleus (AMN) stimulation on adult hippocampal neurogenesis in awake and unrestrained rats. Four groups of adult Sprague-Dawley male and female rats received unilateral stimulation (n = 6 each) or sham surgery (n = 4 each) in the right AMN; another group of males (n = 4) was stimulated in the right ventral posterolateral thalamic nucleus (VPL). A naive group of males and females (n = 4 each) was also included. Rats received 4 injections (50 mg/kg/injection) of 5'-bromo-2'-deoxyuridine (BrdU) 3 days post-surgery and were euthanized 24 h later. The fractionator method was used together with confocal microscopy to count BrdU, GFAP and NeuN positive cells in the dentate gyrus (DG) and hilar zone of the hippocampus. Focal neurogenesis was induced in the ipsilateral DG after AMN but not VPL stimulation. Stimulation-induced effects were sex-independent and translated into a 76% increase in proliferation of neural stem/progenitor cells. Increased neurogenesis was most prominent at the caudal region of the DG, while no effect was detected in the hilar and the subventricular zones. The exclusive hippocampal neurogenic response to AMN stimulation suggests an involvement of the Papez circuitry in mediating DBS effects and in the treatment of cognitive and behavioral disorders.

Motor cortex stimulation and neuropathic pain: how does motor cortex stimulation affect pain-signaling pathways?

Neuropathic pain is often severe. Motor cortex stimulation (MCS) is used for alleviating neuropathic pain, but the mechanism of action is still unclear. This study aimed to understand the mechanism of action of MCS by investigating pain-signaling pathways, with the expectation that MCS would regulate both descending and ascending pathways. Neuropathic pain was induced in Sprague-Dawley rats. Surface electrodes for MCS were implanted in the rats. Tactile allodynia was measured by behavioral testing to determine the effect of MCS. For the pathway study, immunohistochemistry was performed to investigate changes in c-fos and serotonin expression; micro-positron emission tomography (mPET) scanning was performed to investigate changes of glucose uptake; and extracellular electrophysiological recordings were performed to demonstrate brain activity. MCS was found to modulate c-fos and serotonin expression. In the mPET study, altered brain activity was observed in the striatum, thalamic area, and cerebellum. In the electrophysiological study, neuronal activity was increased by mechanical stimulation and suppressed by MCS. After elimination of artifacts, neuronal activity was demonstrated in the ventral posterolateral nucleus (VPL) during electrical stimulation. This neuronal activity was effectively suppressed by MCS. This study demonstrated that MCS effectively attenuated neuropathic pain. MCS modulated ascending and descending pain pathways. It regulated neuropathic pain by affecting the striatum, periaqueductal gray, cerebellum, and thalamic area, which are thought to regulate the descending pathway. MCS also appeared to suppress activation of the VPL, which is part of the ascending pathway.

Thalamic Reorganization in Chronic Patients With Intracerebral Hemorrhage: A Retrospective Cross-Sectional Study.

The aim of this study was to investigate changes of synaptic area of the spinothalamic tract and its thalamocortical pathway (STT) in the thalamus in chronic patients with putaminal hemorrhage.Twenty four patients with a lesion in the ventral posterior lateral nucleus (VPL) of the thalamus following putaminal hemorrhage were recruited for this study. The subscale for tactile sensation of the Nottingham Sensory Assessment (NSA) was used for the determination of somatosensory function. Diffusion tensor tractography of the STT was reconstructed using the Functional Magnetic Resonance Imaging of the Brain Software Library. We classified patients according to 2 groups: the VPL group, patients whose STTs were synapsed in the VPL; and the non-VPL group, patients whose STTs were synapsed in other thalamic areas, except for the VPL.Thirteen patients belonged to the VPL group, and 8 patients belonged to the non-VPL group. Three patients were excluded from grouping due to interrupted integrity of the STTs. The tactile sensation score of the NSA in the non-VPL group (10.50 ± 0.93) was significantly decreased compared with that of the VPL group (19.45 ± 1.33) (P < 0.05).We found that 2 types of patient had recovered via the VPL area or other areas of the STT. It appears that patients who showed shifting of the thalamic synaptic area of the STT might have recovered by the process of thalamic reorganization following thalamic injury. In addition, thalamic reorganization appears to be related to poorer somatosensory outcome.

Characteristics of thalamic local field potentials in patients with disorders of consciousness.

A functioning thalamus is essential for treatment of patients with disorders of consciousness (DOC) using deep brain stimulation (DBS). This work aims to identify the potential biomarkers related to consciousness from the thalamic deep brain local field potentials (LFPs) in DOC patients. The frequency features of central thalamic LFPs were characterized with spectral analysis. The features were further compared to those of LFPs from the ventroposterior lateral nucleus of the thalamus (VPL) in patients with pain. There are several distinct characteristics of thalamic LFPs found in patients with DOC. The most important feature is the oscillation around 10Hz which could be relevant to the existence of residual consciousness, whereas high power below 8Hz seemed to be associated with loss of consciousness. The invasive deep brain recording tool opens a unique way to explore the brain function in consciousness, awareness and alertness and clarify the potential mechanisms of thalamic stimulation in DOC.

Distinction in the immunoreactivities of two calcium-binding proteins and neuronal birthdates in the first and higher-order somatosensory thalamic nuclei of mice: Evolutionary implications.

Comparative embryonic studies are the most effective way to discern phylogenetic changes. To gain insight into the constitution and evolution of mammalian somatosensory thalamic nuclei, we first studied how calbindin (CB) and parvalbumin (PV) immunoreactivities appear during embryonic development in the first-order relaying somatosensory nuclei, i.e., the ventral posteromedial (VPM) and posterolateral (VPL) nuclei, and their neighboring higher-order modulatory regions, including the ventromedial or ventrolateral nucleus, posterior, and the reticular nucleus. The results indicated that cell bodies that were immunoreactive for CB were found earlier (embryonic day 12 [E12]) in the dorsal thalamus than were cells positive for PV (E14), and the adult somatosensory thalamus was characterized by complementary CB and PV distributions with PV dominance in the first-order relaying nuclei and CB dominance in the higher-order regions. We then labeled proliferating cells with [(3) H]-thymidine from E11 to 19 and found that the onset of neurogenesis began later (E12) in the first-order relaying nuclei than in the higher-order regions (E11). Using double-labeling with [(3) H]-thymidine autoradiography and CB or PV immunohistochemistry, we found that CB neurons were born earlier (E11-12) than PV neurons (E12-13) in the studied areas. Thus, similar to auditory nuclei, the first and the higher-order somatosensory nuclei exhibited significant distinctions in CB/PV immunohistochemistry and birthdates during embryonic development. These data, combined with the results of a cladistic analysis of the thalamic somatosensory nuclei, are discussed from an evolutionary perspective of sensory nuclei.

Deep brain stimulation of the dorsal anterior cingulate cortex for the treatment of chronic neuropathic pain.

Chronic neuropathic pain is estimated to affect 3%-4.5% of the worldwide population. It is associated with significant loss of productive time, withdrawal from the workforce, development of mood disorders such as depression and anxiety, and disruption of family and social life. Current medical therapeutics often fail to adequately treat chronic neuropathic pain. Deep brain stimulation (DBS) targeting subcortical structures such as the periaqueductal gray, the ventral posterior lateral and medial thalamic nuclei, and the internal capsule has been investigated for the relief of refractory neuropathic pain over the past 3 decades. Recent work has identified the dorsal anterior cingulate cortex (dACC) as a new potential neuromodulation target given its central role in cognitive and affective processing. In this review, the authors briefly discuss the history of DBS for chronic neuropathic pain in the United States and present evidence supporting dACC DBS for this indication. They review existent literature on dACC DBS and summarize important findings from imaging and neurophysiological studies supporting a central role for the dACC in the processing of chronic neuropathic pain. The available neurophysiological and empirical clinical evidence suggests that dACC DBS is a viable therapeutic option for the treatment of chronic neuropathic pain and warrants further investigation.

Temporal pattern of neurodegeneration, programmed cell death, and neuroplastic responses in the thalamus after lateral fluid percussion brain injury in the rat.

The effects of traumatic brain injury (TBI) on the thalamus are not well characterized. We analyzed neuronal degeneration and loss, apoptosis, programmed cell death-executing pathways, and neuroplastic responses in the rat thalamus during the first week after lateral fluid percussion injury (LFPI). The most prominent neurodegenerative and neuroplastic changes were observed in the region containing the posterior thalamic nuclear group and ventral posteromedial and posterolateral thalamic nuclei ipsilateral to the LFPI. There was progressive neurodegeneration in these regions, with maximal neuronal loss on Day 7. Increases in numbers of apoptotic cells were detected on Day 1 and were enhanced on Days 3 and 7 after TBI. There was unchanged expression of active caspase-3 at all postinjury time points, but there was increased expression of apoptosis-inducing factor (AIF) on Day 7. The AIF nuclear translocation was detected on Day 1 and was maximal on Day 7. Total thalamic synaptophysin expression was unchanged, but immunostaining intensities were increased at all time points after TBI. Decreased growth-associated protein-43 expression and signal intensity were observed on Day 1. Our results suggest that progressive neuronal damage and loss, AIF signaling pathway-dependent programmed cell death, and limited neuroplastic changes occur in the rat thalamus during the first week after LFPI induction.

PTU-190 Dissociation of upper limb temperature sensation in functional gastrointestinal disorders compared to blood relatives and unrelated controls

<h3>Introduction</h3> Temperature sensations from the upper limbs are transmitted through the contralateral spinothalamic tract in the cord to the ventral posterior lateral nucleus of the thalamus and then the primary somatic sensory cortex. Autonomic dysfunction arising in the central nervous system is known to affect the sympathetic function of skin which can result in a unilateral dissociation of temperature sensation. Autonomic dysfunction is also increasingly being hypothesised as a component of the functional gastrointestinal disorders (FGIDs). <h3>Aims</h3> To assess the bilateral upper limb temperature sensation of a consecutive cohort of FGID patients and compare the incidence of temperature dissociation with controls. <h3>Method</h3> Clinic attenders with a FGID diagnosis were sequentially invited to undertake the temperature sensation test. This comprised holding a bag of ice in both hands for 5 s and stating if they perceived the temperature to be either unilaterally colder or bilaterally equally cold. Unilaterally colder was considered to be evidence of upper limb temperature sensory dissociation. If a relative, spouse or friend was present they were also invited to participate as either a blood relative or un-related control. <h3>Results</h3> 58 FGID patients and 58 controls undertook the temperature sensation test. 42 patients (72.4%) had upper limb temperature dissociation compared with 20 controls (34.4%) [P = 0.005]. 18/22 (81.8%) patients had dissociation compared to 8/22 (36.3%) blood relative controls [P = 0.049], and 24/36 (66.6%) patients had dissociation compared to 12/36 (33.3%) unrelated controls [P = 0.045]. There was no significant difference in the incidence of dissociation between blood relatives and unrelated controls, 36.3% and 33.3% respectively [P = 0.84]. <h3>Conclusion</h3> Upper limb temperature dissociation seems to be more prevalent in patients with FGIDs than their blood relatives or unrelated controls. It may be associated with autonomic dysfunction as a result of a central nervous process. These findings are an interesting observation in our clinic, but do not constitute formal research and are limited by possible biases (selection and assessment) and a relatively small sample size. The observed proportions of temperature dissociation in these groups could be used to calculate an adequate sample size to detect whether this may be true in a formal research study of autonomic dysfunction in FGIDs. <h3>Disclosure of interest</h3> None Declared.

At the centre of neuronal, synaptic and axonal pathology in murine prion disease: degeneration of neuroanatomically linked thalamic and brainstem nuclei.

AimsThe processes by which neurons degenerate in chronic neurodegenerative diseases remain unclear. Synaptic loss and axonal pathology frequently precede neuronal loss and protein aggregation demonstrably spreads along neuroanatomical pathways in many neurodegenerative diseases. The spread of neuronal pathology is less studied.MethodsWe previously demonstrated severe neurodegeneration in the posterior thalamus of multiple prion disease strains. Here we used the ME7 model of prion disease to examine the nature of this degeneration in the posterior thalamus and the major brainstem projections into this region.ResultsWe objectively quantified neurological decline between 16 and 18 weeks post‐inoculation and observed thalamic subregion‐selective neuronal, synaptic and axonal pathology while demonstrating relatively uniform protease‐resistant prion protein (PrP) aggregation and microgliosis across the posterior thalamus. Novel amyloid precursor protein (APP) pathology was particularly prominent in the thalamic posterior (PO) and ventroposterior lateral (VPL) nuclei. The brainstem nuclei forming the major projections to these thalamic nuclei were examined. Massive neuronal loss in the PO was not matched by significant neuronal loss in the interpolaris (Sp5I), while massive synaptic loss in the ventral posteromedial nucleus (VPM) did correspond with significant neuronal loss in the principal trigeminal nucleus. Likewise, significant VPL synaptic loss was matched by significant neuronal loss in the gracile and cuneate nuclei.ConclusionThese findings demonstrate significant spread of neuronal pathology from the thalamus to the brainstem in prion disease. The divergent neuropathological features in adjacent neuronal populations demonstrates that there are discrete pathways to neurodegeneration in different neuronal populations.

The neuromodulation of neuropathic pain by measuring pain response rate and pain response duration in animal.

ObjectiveNeuropathic pain causes patients feel indescribable pain. Deep Brain Stimulation (DBS) is one of the treatment methods in neuropathic pain but the action mechanism is still unclear. To study the effect and mechanism of analgesic effects from DBS in neuropathic pain and to enhance the analgesic effect of DBS, we stimulated the ventral posterolateral nucleus (VPL) in rats.MethodsTo observe the effect from VPL stimulation, we established 3 groups : normal group (Normal group), neuropathic pain group (Pain group) and neuropathic pain+DBS group (DBS group). Rats in DBS group subjected to electrical stimulation and the target is VPL.ResultsWe observed the behavioral changes by DBS in VPL (VPL-DBS) on neuropathic pain rats. In our study, the pain score which is by conventional test method was effectively decreased. In specific, the time of showing withdrawal response from painful stimulation which is not used measuring method in our animal model was also decreased by DBS.ConclusionThe VPL is an effective target on pain modulation. Specifically we could demonstrate changes of pain response duration which is not used, and it was also significantly meaningful. We thought that this study would be helpful in understanding the relation between VPL-DBS and neuropathic pain.

Function of Nucleus Ventralis Posterior Lateralis Thalami in Acupoint Sensitization Phenomena

To observe the effect of electroacupuncture (EA) on nucleus ventralis posterior lateralis (VPL) thalami activated by visceral noxious stimulation and to explore the impact of EA on the mechanism of acupoint sensitization under a pathological state of the viscera, EA was applied at bilateral “Zusanli-Shangjuxu” acupoints. The discharge of VPL neurons was response to EA increased after colorectal distension (CRD). The stimulation at “Zusanli-Shangjuxu” acupoints enhanced discharge activity of VPL neurons under CRD-induced visceral pain. The frequency of neuronal discharge was associated with the pressure gradient of CRD which showed that visceral noxious stimulation may intensify the body's functional response to stimulation at acupoints.

Microstimulation: Principles, Techniques, and Approaches to Somatosensory Neuroprosthesis.

The power of movement of electrically charged particles has been used to alleviate an array of illnesses and help control some human body parts. Microstimulation, the electrical current-driven excitation of neural elements, is now being aimed at brain-machine interfaces (BMIs), brain-controlled external devices that improve quality of life for people such as those who have lost the ability to use their limbs. This effort is motivated by behavioral experiments that indicate a direct link between microstimulation-induced sensory experience and behavior, pointing to the possibility of optimizing and controlling the outputs of BMIs. Several laboratories have focused on using electrical stimulation to return somatosensory feedback from prosthetic limbs directly to the user's central nervous system. However, the difficulty of the problem has led to limited success thus far, and there is a need for a better understanding of the basic principles of neural microstimulation. This article provides a review of the available literature and some recent work at Downstate Medical Center and Columbia University on microstimulation of the primate and rodent somatosensory (S1) cortex and the ventral posterolateral thalamus. It is aimed at contributing to the existing knowledge base to generate good behavioral responses and effective, BMI-appropriate somatosensory feedback. In general, the threshold for the particular brain tissue in response to current-amplitude has to be determined by rigorous experimentation. For consistently reproducible results, hardware and thresholds for microstimulation have to be specified. In addition, effects on motor functions, including unwanted side effects in response to the microstimulation of brain tissue, must be examined to take the field from bench to bedside.