Field Of Innervation Research Articles

Pain propagation in the carpal tunnel syndrome: a quantitative sensory testing

<p><strong>Aim</strong> To determine the existence of damage to thin sensitive fibres (Aδ and C) by quantitative sensory testing (QST) in female patients with carpal tunnel syndrome (CTS), the existence of pain, and a connection with the in-nervation field of the nerve itself.<br /><strong>Methods</strong> Forty-two consecutive female patients with symptoms of CTS participated in the research. According to the clinical findings and electroneurography they were divided into group I of 22 women with confirmed CTS and group II of 20 women with non-confirmed disease. Using QST, the threshold of heat and cold, and the threshold of pain caused by heat and cold on the thenar, second, and third finger of the dominant hand in both groups was determined. <br /><strong>Results</strong> There was a statistically significant difference in group I for the threshold of heat and cold detection and the threshold of pain caused by heat and cold between the thenar and the fingers. In the group II, there was a statistically significant difference in the threshold of heat detection between the thenar and the fingers. There was a statistically significant difference between the groups in the threshold of heat and cold detection on the fingers and the threshold of pain induced by heat on the fingers. <br /><strong>Conclusion</strong> In the carpal tunnel syndrome, there was damage to thin Aδ and C fibers in the innervation field of the median nerve, which causes pain within the innervation field of the nerve, but also outside it, which can most likely be a consequence of brain plasticity and central sensitization.</p>

An anatomical variant of the posterior branch of the great auricular nerve: A case report and a short review of the literature

The great auricular nerve (GAN) is a sensory cutaneous nerve, which provides sensory innervation to the skin overlaying auricle, parotid gland, and mastoid region. The emergency of GAN is located at Erb’s point over the posterior burden of the belly of the sternocleidomastoid muscle (SCM). During its course, it normally bifurcates in a pair of, respectively, posterior and anterior, branches. The latter one then further divides into superficial and deep branches. Some different anatomical patterns of GAN branches were reported in the literature to underline the high variability of the GAN course. The aim of this case report is to underline a particular anatomical variant of a posterior branch of GAN we recently observed. It was characterized by an anomalous bifurcation involving two different groups of fibers, within the same field of innervation, which had an independent course toward the auricular lobe. To promptly face such a somewhat unexpected anomaly, besides the basic recommendation to surgeons of mastering a good knowledge of the high variability of the anatomy of GAN, a careful dissection around the SCM is believed to help the surgeon to recognize other anatomical variants of GAN course with the aim to preserve it.

In Search for the Avian Trigeminal Magnetic Sensor: Distribution of Peripheral and Central Terminals of Ophthalmic Sensory Neurons in the Night-Migratory Eurasian Blackcap (Sylvia atricapilla).

In night-migratory songbirds, neurobiological and behavioral evidence suggest the existence of a magnetic sense associated with the ophthalmic branch of the trigeminal nerve (V1), possibly providing magnetic positional information. Curiously, neither the unequivocal existence, structural nature, nor the exact location of any sensory structure has been revealed to date. Here, we used neuronal tract tracing to map both the innervation fields in the upper beak and the detailed trigeminal brainstem terminations of the medial and lateral V1 subbranches in the night-migratory Eurasian Blackcap (Sylvia atricapilla). The medial V1 subbranch takes its course along the ventral part of the upper beak to innervate subepidermal layers and the mucosa of the nasal cavity, whereas the lateral V1 subbranch runs along dorsolateral levels until the nostrils to innervate mainly the skin of the upper beak. In the trigeminal brainstem, medial V1 terminals innervate both the dorsal part and the ventral, magnetically activated part of the principal sensory trigeminal brainstem nuclei (PrV). In contrast, the lateral V1 subbranch innervates only a small part of the ventral PrV. The spinal sensory trigeminal brainstem nuclei (SpV) receive topographically ordered projections. The medial V1 subbranch mainly innervates rostral and medial parts of SpV, whereas the lateral V1 subbranch mainly innervates the lateral and caudal parts of SpV. The present findings could provide valuable information for further analysis of the trigeminal magnetic sense of birds.

Nervous system and internal secretion. Collection of works of the morphological sector of the Institute for the study of the brain named after V. M. Bekhterev. P. 84. Price 3 rubles. Lenogiz, 1932

Prof. L. Ya. Pine s, whose name became known far beyond the borders of the USSR thanks to his outstanding work in the field of innervation of the endocrine glands, gives in the collection a generalization of the head. them by the sector of normal histological data on the innervation of the endocrine glands and a number of works by the employees of the sector that replenish this data. The collection contains a preface by Pines, 7 articles (L. Pines, Narovchatova, R. Maiman, I. Pis, M. Sheftel, B. Shapiro, M. Kurepin) and the minutes of the meetings of the morphology sector of the I-that of the brain for 1930/31 G.

Integrated phylogeny of the human brain and pathobiology of Alzheimer’s disease: A unifying hypothesis

The disproportionate evolutionary expansion of the human cerebral cortex with reinforcement of cholinergic innervations warranted a major rise in the functional and metabolic load of the conserved basal forebrain (BF) cholinergic system. Given that acetylcholine (ACh) regulates properties of the microtubule-associated protein (MAP) tau and promotes non-amyloidogenic processing of amyloid precursor protein (APP), growing neocortex predicts higher demands for ACh, while the emerging role of BF cholinergic projections in Aβ clearance infers greater exposure of source neurons and their innervation fields to amyloid pathology. The higher exposure of evolutionary most recent cortical areas to the amyloid pathology of Alzheimer’s disease (AD) with synaptic impairments and atrophy, therefore, might involve attenuated homeostatic effects of BF cholinergic projections, in addition to fall-outs of inherent processes of expanding association areas. This unifying model, thus, views amyloid pathology and loss of cholinergic cells as a quid pro quo of the allometric evolution of the human brain, which in combination with increase in life expectancy overwhelm the fine homeostatic balance and set off the disease process.

Билатеральная компрессия срединного нерва апоневрозом двуглавой мышцы плеча на уровне локтевого сустава (Лацертус-синдром)

Lacertus fibrosus entrapment of the median nerve at the elbow, or Lacertus syndrome, is a rare pathology, which is difficult to detect by instrumental examination methods. Literary sources provide no information on the syndrome prevalence, as well as on precise diagnosis and treatment algorithms, which makes it difficult to establish the diagnosis and appoint the effective treatment. Lacertus syndrome is characterized by positive scratch collapse test; differential diagnosis is required to distinguish it from carpal tunnel syndrome. Clinical case of bilateral lacertus fibrosus entrapment of the median nerve at the elbow is reported, Lacertus syndrome diagnosis criteria and surgical treatment method are set out. The results of the surgical tactics used are as follows: pain, paresthesia and numbness in the innervation field of the median nerve have vanished, the muscle strength has been restored to level М5 in accordance with MRC muscle strength scale. These results demonstrate high efficiency of the proposed lacertus syndrome surgical treatment.

Development of serotonergic projections to the suprachiasmatic nucleus in the mouse brain

Serotonin (5-HT) and its innervation have been implicated in various neural functions including circadian systems. Although classical studies have examined the 5-HT innervation pattern in the adult suprachiasmatic nucleus (SCN), the fine-grained morphological study of the development of pathway and terminal projections to the SCN remains scarce. Here, we utilize transgenic mice expressing GFP under the serotonin transporter (SERT) promoter to subserve our developmental mapping study. We demonstrate that the morphology of 5-HT pathway fibers decussating over the supraoptic commissure that projects to the SCN exhibits two distinct developmental patterns. The punctate fibers at the fetal stage gradually become smooth and filamentous, especially during postnatal one week and remain constant thereafter. The innervation field in the SCN develops properly only during postnatal two weeks. Its ventromedial area remains one of the highest 5-HT innervated areas in the adult brain, whereas the dorsolateral area is less innervated. Thus, we provide novel and specific insights on the developmental map of 5-HT system into the SCN using transgenic mouse.

Motivational nondirective resonance breathing versus transcutaneous vagus nerve stimulation in the treatment of fibromyalgia: study protocol for a randomized controlled trial

BackgroundChronic widespread pain (CWP), including fibromyalgia (FM), affects one in every ten adults and is one of the leading causes of sick leave and emotional distress. Due to an unclear etiology and a complex pathophysiology, FM is a condition with few, if any, effective and safe treatments. However, current research within the field of vagal nerve innervation suggests psychophysiological and electrical means by which FM may be treated. This study will investigate the efficacy of two different noninvasive vagal nerve stimulation techniques for the treatment of FM.MethodsThe study will use a randomized, single-blind, sham-controlled design to investigate the treatment efficacy of motivational nondirective resonance breathing (MNRB™) and transcutaneous vagus nerve stimulation (Nemos® tVNS) on patients diagnosed with FM. Consenting FM patients (N = 112) who are referred to the Department of Pain Management and Research at Oslo University Hospital, in Oslo, Norway, will be randomized into one of four independent groups. Half of these participants (N = 56) will be randomized to either an experimental tVNS group or a sham tVNS group. The other half (N = 56) will be randomized to either an experimental MNRB group or a sham MNRB group. Both active and sham treatment interventions will be delivered twice per day at home, 15 min/morning and 15 min/evening, for a total duration of 2 weeks (14 days). Participants are invited to the clinic twice, once for pre- and once for post-intervention data collection. The primary outcome is changes in photoplethysmography-measured heart rate variability. Secondary outcomes include self-reported pain intensity on a numeric rating scale, changes in pain detection threshold, pain tolerance threshold, and pressure pain limit determined by computerized pressure cuff algometry, blood pressure, and health-related quality of life.DiscussionThe described randomized controlled trial aims to compare the efficacy of two vagal nerve innervation interventions, MNRB and tVNS, on heart rate variability and pain intensity in patients suffering from FM. This project tests a new and potentially effective means of treating a major public and global health concern where prevalence is high, disability is severe, and treatment options are limited.Trial registrationClinicalTrials.govNCT03180554. Registered on August 06, 2017.

Muscle fiber-type specific terminal Schwann cell pathology leads to sprouting deficits following partial denervation in SOD1G93A mice

Amyotrophic lateral sclerosis (ALS) is an adult-onset disease characterized by the progressive death of motoneurons and denervation of muscle fibers. To restore motor function, surviving motoneurons in partially denervated muscles typically sprout axons to reinnervate denervated endplates. However, studies on the SOD1G93A rodent models of ALS indicate that sprouting is significantly limited in fast, but not slow, twitch muscles after disease onset. This limitation hastens the rate of muscle weakness and loss of motor function. The causes of this limitation are currently unknown. Sprouting could be limited because the SOD1G93A mutation weakens motoneurons making them incapable of expanding their field of innervation. Alternatively, motoneurons may be capable of sprouting, but unable to do so due to the loss of a permissive sprouting environment. To distinguish between the two possibilities, we compared the sprouting capacity of motoneuron subtypes by partially denervating the fast twitch plantaris (composed of type IIa/IIb muscle fibers) and slow twitch soleus muscles (type I/IIa fibers) prior to disease onset and weakening in SOD1G93A and WT mice. We found that only motoneurons innervating the SOD1G93A plantaris had a limited sprouting capacity. This was correlated with the selective loss of terminal Schwann cells (TSCs) at IIb fibers and an increase in macrophage infiltration. Treating SOD1G93A mice with the tyrosine kinase inhibitor, masitinib, significantly reduced infiltration, prevented TSC loss, and increased the sprouting capacity to near normal. These results suggest that TSCs at denervated type IIb muscle fibers are aberrantly targeted by infiltrating macrophages in SOD1G93A mice, and their loss accounts, at least in part, for the compromised sprouting capacity of the largest motoneurons during early stages of ALS.

Модифицированный способ ментальной анестезии по методу маламед с применением устройства Ушницкого-Чахова

Nowadays the dental help quality improvement to the population is important. Constant search of effective methods of local anesthesia is a relevant issue. Aim. The objective is to develop the modified way of mental anesthesia by S. Malamed technique on the basis of complex craniometrical, radiological and clinical researches. Materials and methods. Anatomical-topographical features of mental foramen of 91 mandibular bones have been studied. Besides, computer tomography results (82 images) were applied to study mental foramen topography. The obtained data made a basis for development of Ushnitsky-Chakhov’s device for carrying out mental anesthesia by S. Malamed technique and to modify mental anesthesia by S. Malamed technique where blockade of incisal branch of the lower alveolar and mental nerves was carried out at 51 patients. Results. The complex anatomical-topographic examination of the anterior width, altitudes of the symphysis and mandibula body, as well as the distance from the upper edge of the mental foramen to the occlusal surface and distance from the lower edge of the mental foramen to the lower edge of the mandibula has revealed the presence of variability of their indices. On the basis of the received results we have developed the device for carrying out mental anesthesia by S. Malamed technique which was applied to blockade incisal branch of the lower alveolar and mental nerves. The clinical assessment and analysis have revealed certain advantages of this device use, connected with more exact individual definition of topography of a mental foramen and depth of immersion of a needle that is not always considered when carrying out mental anesthesia by S. Malamed technique. At the same time the lasting effect of anesthesia in the field of innervation of mental and incisal branch of lower alveolar nerves is observed in 5-7 minutes. At the same time the zone of anesthesia corresponds to a standard technique of mental anesthesia by S. Malamed technique. Conclusions. The modified way of mental anesthesia by S. Malamed technique with use of Ushnitsky-Chakhov’s device for carrying out mental anesthesia provides more exact determination of immersion depth of a syringe needle to a mental foramen taking into account specific features that minimizes trauma of mental neurovascular bunch and increases analgesic effect

Spatial relationship between the c-Fos distribution and enkephalinergic, substance P, and tyrosine hydroxylase innervation fields after acute treatment with neuroleptics olanzapine, amisulpride, quetiapine, and aripiprazole in the rat septum.

The aim of the present study was to demonstrate the spatial relationship between the c-Fos immunoreactive cells elicited by an acute treatment with neuroleptics including amisulpride (AMI), olanzapine (OLA), quetiapine (QUE), and aripiprazole (ARI) and enkephalinergic (ENK), substance P (SP), and tyrosine hydroxylase (TH) innervation fields in the rat septum. Male Sprague Dawley rats received a single injection of OLA (5 mg), ARI (10 mg), AMI (20 mg), QUE (15 mg/kg/b.w.). Ninety min after antipsychotics administration, the animals were transcardially perfused with a fixative and the brains cryocut into serial coronal sections of 35 µm thickness. The sections were processed for c-Fos staining using an avidin-biotin-peroxidase complex and visualized by nickel intensified diaminobenzidine to reach black endproduct. Afterwards, the sections were exposed to ENK, SP, and TH antibodies and the reaction product visualized by biotin-labeled fluorescent AlexaFluor 564 dye. The data were evaluated from the sections either simultaneously illuminated with fluorescent and transmission microscope beams or after merging the separately illuminated sections in the Adobe Photoshop 7.0 software. ENK, SP, and TH displayed characteristic spatial images formed by a dense accumulation of immunoreactive fibers and terminals on the both sides of the septum. A dense plexus of axons formed by ENK and SP immunopositive terminals were situated predominantly in the lateral, while TH ones more medial portion of the septum. QUE and AMI activated distinct amount of c-Fos expression in cells located within the SP-immunoreactive principal innervation field. The OLA effect on the c-Fos expression was very pronounced in the ventral TH-labeled principal innervation field including the space between the ENK field ventral portion and the dorsal margin of the accumbens nucleus shell. Generally, the occurrence of c-Fos cells in the ENK-immunoreactive principal innervation field, in comparison with the surrounding septal area, was less abundant after all of the four antipsychotics treatments. The data of the present study indicate that ENK, SP, and TH innervation fields may influence separate populations of septal cells activated by AMI, OLA, QUE, and ARI and that each of these region-differently innervated cells may be associated with the functional heterogeneity of the individual lateral septal nuclei.

The Morphology of the Infraorbital Nerve and Foramen in the Presence of an Accessory Infraorbital Foramen.

The accessory infraorbital foramen (AIOF) is an anatomical variation associated with the infraorbital foramen (IOF) and nerve (ION). Its occurrence and neural contents have clinical implications regarding failure of loco-regional anesthesia and risk of neural damage during surgical interventions involving the maxillary region. Thus, morphologic characterization of the AIOF and neural contents as well as the spatial relationships to the IOF are potentially useful for optimizing surgical procedures. Additionally, predictive features of the AIOF based on its relationship to IOF morphology could enable the surgeon to anticipate its presence and proceed accordingly. The purpose of this study was to determine whether the presence of an AIOF and its neural contents affected the size, shape, and composition of the IOF and ION. The specific hypothesis tested was that the topography and fascicular composition of the ION and IOF differs between individuals possessing an AIOF and those lacking this anatomical variant. Gross topographic features of the IOF (42 crania) were compared between specimens possessing (test) or lacking (control) an AIOF. Nerve fascicles of ION (60 cadaveric sides) were examined histologically and compared morphometrically between specimens presenting or lacking an AIOF. An additional sample of 30 crania was subjected to cone-beam computed tomography (CBCT) analysis to determine the course of the canal leading to the AIOF. The AIOF incidence was 47.6% (20 crania) and 32.1% of the sides (27 sides). A single AIOF was observed in 24 sides and double AIOF in three sides. The AIOF occurred bilaterally in 7 specimens (16.7%). The majority of AIOF (86.7%) were located superomedial to IOF. A slightly higher frequency of the AIOF was found in left side compared to the right. Using CBCT, a patient sample showed an AIOF incidence in 21 sides of 16 patients (65.6%). A single AIOF was observed in 19 sides. Only 1 double AIOF was found in the scans, whereas 3 were found in the dry skull group. The AIOF occurred bilaterally in 3 scans (10%). The majority of AIOF (90.4%) were located superomedial to the IOF based on the CBCT scans. The AIOF was consistently seen connected to the infraorbital canal and progressed superiorly and medially from the infraorbital canal to the maxillary surface. The size of the ION without an AIOF was not significantly different than the ION in the presence of an AIOF (1.45 × 10/1.32 × 10 μm, P < 0.35) based on fascicular area. However, the number of ION fascicles was greater in specimens without an AIOF compared to those showing this feature (15.15/12.71, P < 0.04) CONCLUSION:: Results indicate that the area of the ION is not affected by an AIOF, suggesting that the field of innervation of this area is not modified by its occurrence. However, the ION appears to divide more proximally into its component branches when the AIOF is present.

Патологический нейрогенез - ключевое звено патогенеза тазовой боли, обусловленной аденомиозом

Статья посвящена одной из актуальных проблем клинической гинекологии - тазовой боли при аденомиозе. Цель исследования: изучение морфологических особенностей нервного аппарата миометрия у женщин с синдромом хронической тазовой боли, обусловленной аденомиозом. Методика. Изучено 60 биоптатов, полученных после гистерэктомий у женщин с диффузным аденомиозом ІІ-ІІІ степени, сопровождающимся болевым синдромом выраженной степени тяжести, не получавших гормональную терапию. Группа морфологического сравнения составила 10 биоптатов, полученных у женщин с аденомиозом, без болевого синдрома, прооперированных по поводу аномальных маточных кровотечений, также не получавших гормональную терапию. У всех пациентов получено информированное согласие на использование биологического материала в исследовании. После гистерэктомии участки стенок маток, включавшие эндометрий и миометрий подвергали стандартным гистологическим процедурам, готовили парафиновые срезы (5 мкм). Общую морфологическую оценку проводили при окраске срезов гематоксилином и эозином. Визуализацию нервных волокон осуществляли после иммуногистохимического (ИГХ) окрашивания с использованием моноклональных антител (МАТ) к белкам нейрофиламентов (DAKO, Дания) по инструкциям фирмы. Результаты. Изучение иннервационного аппарата матки при аденомиозе с помощью моноклональных антител к белкам нейрофиламентов выявил разнообразие волокон по толщине, плотности и интенсивности окраски. Плотность нервных окончаний, сопряженных непосредственно с очагами эндометриоза, была невелика - в зоне желез 4,1 ± 0,3 на мм среза, в строме - 9,2 ± 0,6. Тонкие нервные волокна визуализировались преимущественно в строме вокруг кровеносных сосудов, сопровождающих зоны врастания эктопического эндометрия. Густое сплетение тонких нервных волокон также было обнаружено в субсерозном слое. Причем, как в субсерозном, так и в подслизистом слое миометрия превалировали разветвленные тонкие нервные волокна, количество которых статистически значимо (p&lt;0,01) превышало аналогичный показатель в группе сравнения - 17,2 ± 1,4 против 11,8 ± 0,9 на мм. Сравнение иннервационного аппарата матки у женщин контрольной группы и у пациенток с аденомиозом с болевым синдромом позволяет утверждать, что именно расширение иннервационного поля в миометрии является наиболее вероятной причиной формирования тазовой боли у пациенток с аденомиозом. Выводы. Результаты проделанной работы продемонстрировали, что основным местом локализации нервов в матке и потенциальной причиной формирования гипералгезии при аденомиозе является миометрий с формированием аномально избыточного иннервационного аппарата вокруг очагов эктопического эндометрия, в периваскулярных регионах и в строме между пучками гладких миоцитов. Objective. To study morphological features of the myometrium neural apparatus in women with chronic pelvic pain syndrome associated with adenomyosis. Methods. 60 biopsy samples were studied, which were obtained from hysterectomies for grade I-III diffuse adenomyosis associated with severe pelvic pain syndrome. These women did not receive any hormonal therapy. The control group included 10 biopsies obtained from women with adenomyosis who had no pelvic pain syndrome and underwent a surgery for abnormal uterine bleeding. These women did not receive any hormonal therapy either. After hysterectomy, uterine wall samples including endometrium and myometrium were fixed in 10% neutral, buffered formalin (pH 7.4) for 24 hours. After dehydration, the material was embedded in paraffin highly purified with polymeric additives (Richard-Allan Scientific, USA) at a temperature &lt;60°C. Overall morphological evaluation of sections was performed with H E staining. Imaging was performed after nerve fibers immunohistochemical (IHC) staining with monoclonal antibodies (MAbs) to neurofilament proteins (DAKO, Denmark) according to the manufacturer’s instructions. Results. Studying of the uterine innervation apparatus using monoclonal antibodies to neurofilament proteins in adenomyosis identified a variety of fiber thickness, density and color intensity. Density of nerve endings directly associated with endometriosis foci was low; 4.1 ± 0.3 per mm in the glandular zone and 9.2 ± 0.6 per mm in the stroma. Thin nerve fibers were visualized mainly in the stroma around blood vessels associated with the ectopic endometrium ingrowth zone. A dense plexus of thin nerve fibers was also found in the subserosal layer. Furthermore, both in myometrial subserosal and submucosal layers, ramified, thin nerve fibers predominated. The number of such fibers was significantly greater than in the comparison group (17.2 ± 1.4 vs. 11.8 ± 0.9 per mm, p&lt;0.01). Comparison of the uterine innervation apparatus in women with and without chronic pelvic pain syndrome suggested that particularly the expansion of myometrium innervation field was the most likely cause for the development of pelvic pain in women with adenomyosis. Conclusions. The main location of uterine nerves and a potential cause for hyperalgesia in adenomyosis is the myometrium developing abnormally excessive innervation around foci of ectopic endometrium, perivascular areas, and the stroma between fibers of smooth myocytes.

Preemptive Local Anesthesia in Ankle Arthroscopy.

Complex anesthesia is increasingly used in order to reduce postoperative pain and accelerate rehabilitation. The aim of this study was to evaluate the efficacy and safety of preemptive local anesthesia combined with general or spinal anesthesia in ankle arthroscopy. From January 2014 to February 2016, 80 ankle anterior arthroscopies were performed. Patients were randomly assigned to one of 4 groups, depending on the type of anesthesia: A, general and local preemptive; B, spinal and local preemptive; C, general and placebo; D, spinal and placebo. After general or spinal anesthesia, each patient randomly received an injection of 7 mL of a mixture of local anesthetics or the same amount of normal saline. After 2, 4, 8, 12, 16, 24, 48, and 72 hours following the release of the tourniquet, the pain intensity level was measured with a visual analog scale (VAS). The use of additional analgesics and any adverse effects were also noted. Preemptive local anesthesia (groups A and B) resulted in a significantly lower level of pain intensity during the first 24 hours after surgery. Until 8 hours after the release of the tourniquet, the pain intensity level was statistically lower in the groups A, B, and D in comparison to C. During hospitalization, none of the patients from groups A and B received on-demand ketoprofen intravenously. No side effects of local anesthetic agents were observed. Two patients had transient numbness and paresthesia in the field of sensory nerve innervation of the dorsal intermediate cutaneous nerve of the foot. Preemptive operative site infiltration with a mixture of local anesthetics performed in ankle arthroscopy was a safe procedure. It reduced the level of intensity of postoperative pain and the amount of analgesics used. Level I, prospective randomized study.

Single-cell genetic expression of mutant GABAA receptors causing Human genetic epilepsy alters dendritic spine and GABAergic bouton formation in a mutation-specific manner.

Mutations in genes encoding for GABAA receptor subunits is a well-established cause of genetic generalized epilepsy. GABA neurotransmission is implicated in several developmental processes including neurite outgrowth and synapse formation. Alteration in excitatory/inhibitory synaptic activities plays a critical role in epilepsy, thus here we investigated whether mutations in α1 subunit of GABAA receptor may affect dendritic spine and GABAergic bouton formation. In particular, we examined the effects of three mutations of the GABRA1 gene (D219N, A322D and K353delins18X) that were found in a cohort of French Canadian families with genetic generalized epilepsy. We used a novel single-cell genetic approach, by preparing cortical organotypic cultures from GABRA1flox/flox mice and simultaneously inactivating endogenous GABRA1 and transfecting mutant α1 subunits in single glutamatergic pyramidal cells and basket GABAergic interneurons by biolistic transfection. We found that GABRA1−/− GABAergic cells showed reduced innervation field, which was rescued by co-expressing α1-A322D and α1-WT but not α1-D219N. We further found that the expression of the most severe GABRA1 missense mutation (α1-A322D) induced a striking increase of spine density in pyramidal cells along with an increase in the number of mushroom-like spines. In addition, α1-A322D expression in GABAergic cells slightly increased perisomatic bouton density, whereas other mutations did not alter bouton formation. All together, these results suggest that the effects of different GABAAR mutations on GABAergic bouton and dendritic spine formation are specific to the mutation and cannot be always explained by a simple loss-of-function gene model. The use of single cell genetic manipulation in organotypic cultures may provide a better understanding of the specific and distinct neural circuit alterations caused by different GABAA receptor subunit mutations and will help define the pathophysiology of genetic generalized epilepsy syndromes.

Presynaptic NCAM is required for motor neurons to functionally expand their peripheral field of innervation in partially denervated muscles.

The function of neural cell adhesion molecule (NCAM) expression in motor neurons during axonal sprouting and compensatory reinnervation was explored by partially denervating soleus muscles in mice lacking presynaptic NCAM (Hb9(cre)NCAM(flx)). In agreement with previous studies, the contractile force of muscles in wild-type (NCAM(+/+)) mice recovered completely 2 weeks after 75% of the motor innervation was removed because motor unit size increased by 2.5 times. In contrast, similarly denervated muscles in Hb9(cre)NCAM(flx) mice failed to recover the force lost due to the partial denervation because motor unit size did not change. Anatomical analysis indicated that 50% of soleus end plates were completely denervated 1-4 weeks post-partial denervation in Hb9(cre)NCAM(flx) mice, while another 25% were partially reinnervated. Synaptic vesicles (SVs) remained at extrasynaptic regions in Hb9(cre)NCAM(flx) mice rather than being distributed, as occurs normally, to newly reinnervated neuromuscular junctions (NMJs). Electrophysiological analysis revealed two populations of NMJs in partially denervated Hb9(cre)NCAM(flx) soleus muscles, one with high (mature) quantal content, and another with low (immature) quantal content. Extrasynaptic SVs in Hb9(cre)NCAM(flx) sprouts were associated with L-type voltage-dependent calcium channel (L-VDCC) immunoreactivity and maintained an immature, L-VDCC-dependent recycling phenotype. Moreover, acute nifedipine treatment potentiated neurotransmission at newly sprouted NMJs, while chronic intraperitoneal treatment with nifedipine during a period of synaptic consolidation enhanced functional motor unit expansion in the absence of presynaptic NCAM. We propose that presynaptic NCAM bridges a critical link between the SV cycle and the functional expansion of synaptic territory through the regulation of L-VDCCs.

Neural Activity and Neurotransmission Regulate the Maturation of the Innervation Field of Cortical GABAergic Interneurons in an Age-Dependent Manner

Neural activity guides the patterning of neuron synaptic territory in the developing nervous system. Evidence supporting this hypothesis comes from numerous studies on projection neurons in neuromuscular and visual systems. It is unknown whether the innervation field of GABAergic interneurons, which forms local dense innervations, follows similar rules. Cortical basket cells innervate hundreds of pyramidal cell somata and proximal dendrites. Thanks to this connectivity pattern, they can tightly control neural excitability and synchronization. Here we show that reducing excitation, and thus neurotransmitter release, in mouse cortical single basket cells in slice cultures decreases the number of innervated cells without changing the pattern of perisomatic innervation, both at the peak and after the proliferation phase of perisomatic synapse formation. Conversely, suppressing neurotransmitter release in single basket cells can have completely opposite effects depending on the developmental stage. Our results reveal a remarkably specific and age-dependent role of neural activity and neurotransmission levels in the establishment of the synaptic territory of cortical GABAergic cells.

Muscle and skin sympathetic activities in Ross syndrome

ObjectivesRoss syndrome (RS) is a rare degenerative disorder characterized by tonic pupil, areflexia and anhydrosis. The underlying lesion affects postganglionic skin sympathetic nerve fibers whereas the postganglionic muscle sympathetic branch is thought to be spared. Microneurography explores both skin and muscle peripheral sympathetic branches and it does not usually detect peripheral sympathetic outflow in either branch in chronic autonomic failure syndromes. The aim of this study was to record sympathetic activity by microneurography for the first time in RS patients to confirm the selective involvement of skin sympathetic nerve activity (SSNA) with spared muscle sympathetic nerve activity (MSNA). MethodsWe studied seven patients (49±14years, four males) with a typical clinical picture and skin biopsy findings. Patients underwent cardiovascular reflexes and microneurography from the peroneal nerve (anhydrotic skin) to record MSNA, SSNA and the corresponding organ effector responses (skin sympathetic response-SSR and skin vasomotor response-SVR) in the same innervation field. The absence of sympathetic bursts was established after exploring at least three different corresponding nerve fascicles. Twenty age-matched healthy subjects served as controls. ResultsRS patients complained of diffuse anhydrosis and they showed tonic pupil and areflexia. Cardiovascular reflexes were normal. All patients displayed absent SSNA, SSR and SVR whereas MSNA was always recorded showing normal characteristics. ConclusionMicroneurographic study of sympathetic activity from affected skin confirmed the selective involvement of skin sympathetic activity with spared muscle sympathetic activity and it may represent the neurophysiological hallmark of the disease. SignificanceMicroneurography together with clinical and skin biopsy findings may contribute to RS diagnosis. Our data also suggest that autonomic damage in RS does not involve cardiovascular activity.

Development of a spinal locomotor rheostat

Locomotion in immature animals is often inflexible, but gradually acquires versatility to enable animals to maneuver efficiently through their environment. Locomotor activity in adults is produced by complex spinal cord networks that develop from simpler precursors. How does complexity and plasticity emerge during development to bestow flexibility upon motor behavior? And how does this complexity map onto the peripheral innervation fields of motorneurons during development? We show in postembryonic Xenopus laevis frog tadpoles that swim motorneurons initially form a homogenous pool discharging single action potential per swim cycle and innervating most of the dorsoventral extent of the swimming muscles. However, during early larval life, in the prelude to a free-swimming existence, the innervation fields of motorneurons become restricted to a more limited sector of each muscle block, with individual motorneurons reaching predominantly ventral, medial, or dorsal regions. Larval motorneurons then can also discharge multiple action potentials in each cycle of swimming and differentiate in terms of their firing reliability during swimming into relatively high-, medium-, or low-probability members. Many motorneurons fall silent during swimming but can be recruited with increasing locomotor frequency and intensity. Each region of the myotome is served by motorneurons spanning the full range of firing probabilities. This unfolding developmental plan, which occurs in the absence of movement, probably equips the organism with the neuronal substrate to bend, pitch, roll, and accelerate during swimming in ways that will be important for survival during the period of free-swimming larval life that ensues.

Microneurographic evaluation of sympathetic activity in small fiber neuropathy

Objective Small fiber neuropathy (SFN) may involve somatic and autonomic fibers. Assessment of somatic epidermal nerve fiber density (ENFs) is considered the gold standard test in the diagnosis of SFN. By contrast, autonomic involvement in SFN is more difficult to ascertain. Here we investigate peripheral sympathetic outflow by microneurography in patients with selective small nerve fiber involvement of different origin with and without autonomic symptoms to ascertain the ability of microneurography and the corresponding skin organ effector responses (sympathetic skin activity-SSR and skin vasomotor reflex-SVR) to disclose autonomic involvement. Methods We studied 59 patients with SFN because of reduced leg ENFs and normal conduction studies. Thirty patients reported only burning paresthesia (somatic SFN) whereas 29 patients complained of additional autonomic dysfunctions (autonomic SFN). They underwent microneurography from peroneal nerve with the recording of muscle sympathetic nerve activity (MSNA), skin sympathetic nerve activity (SSNA) and the corresponding SSR and SVR in the same innervation field. Thirty age and sex-matched healthy subjects served as controls. Results Patients with autonomic SFN mainly complained of loss of sweating. They showed a significant absence of indirect (SSR and SVR) and direct (MSNA and SSNA) sympathetic tests compared to somatic SFN patients and controls. SSNA, SSR and SVR were more often absent than MSNA. In addition, SSR and SVR were absent in all patients with no recordable SSNA but no significant relationship was found with MSNA recording. Conclusions SSR and SVR, simple indirect tests of sympathetic activity, could help to disclose autonomic involvement in SFN with a good sensitivity mainly in patients with sweating dysfunctions although they expressed autonomic failure in only one sympathetic branch. Significance Microneurographic evaluation of sympathetic activity, technically more difficult than indirect tests, was a useful functional tool contributing to the diagnosis and extension of autonomic involvement in SFN. Our data showed that the skin sympathetic branch is more often involved than the muscle sympathetic branch in SFN.