Reticular Formation Research Articles

Cholinergic projections to the preBötzinger complex.

Rhythmic inspiratory activity is generated in the preBötzinger complex (preBötC), a neuronal network located bilaterally in the ventrolateral medulla. Cholinergic neurotransmission affects respiratory rhythmogenic neurons and inhibitory glycinergic neurons in the preBötC. Acetylcholine has been extensively investigated given that cholinergic fibers and receptors are present and functional in the preBötC, are important in sleep/wake cycling, and modulate inspiratory frequency through its action on preBötC neurons. Despite its role in modulating inspiratory rhythm, the source of acetylcholine input to the preBötC is not known. In the present study, we used retrograde and anterograde viral tracing approaches in transgenic mice expressing Cre-recombinase driven by the choline acetyltransferase promoter to identify the source of cholinergic inputs to the preBötC. Surprisingly, we observed very few, if any, cholinergic projections originating from the laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT), two main cholinergic, state-dependent systems long hypothesized as the main source of cholinergic inputs to the preBötC. On the contrary, we identified glutamatergic and GABAergic/glycinergic neurons in the PPT/LDT that send projections to the preBötC. Although these neurons contribute minimally to the direct cholinergic modulation of preBötC neurons, they could be involved in state-dependent regulation of breathing. Our data also suggest that the source of cholinergic inputs to the preBötC appears to originate from cholinergic neurons in neighboring regions of the medulla, the intermediate reticular formation, the lateral paragigantocellularis, and the nucleus of the solitary tract.

Rapid, activity-dependent co-release of GABA and glycine in the mouse brainstem

Presympathetic neurons in the ventrolateral and ventromedial medulla (VLM/VMM) control the sympathetic tone, and GABA was identified as a primary mechanism for sympathoinhibition. Intriguingly, there is evidence that both GABA and glycine efficiently inhibit sympathetic tone; however, the mechanism of glycine release is unknown. In this study, we tested the hypothesis that GABA and glycine are co-released in the VLM/VMM. Glycine is recycled by glycine transporter 2 (GlyT2), which is a reliable marker of glycinergic neurons. Therefore, we crossed heterozygous GlyT2Cre mice with floxed channelrhodopsin 2 (ChR2-EYFP) mice to generate GlyT2 reporter mice (GlyT2ChR2/EYFP), which were used to determine the mechanism of glycine release and reveal the location of glycinergic neurons. Whole-cell patch-clamp recordings from presympathetic VLM/VMM neurons revealed that GABA mediates most spontaneous inhibitory postsynaptic currents (sIPSCs); whereas increased activity of inhibitory inputs promotes the release of glycine. Light stimulation of glycinergic fibers expressing ChR2 in GlyT2ChR2/EYFP mice evoked IPSCs (eIPSCs) with glycinergic and GABAergic components. Bath application of GABAA receptors antagonist (bicuculline, 10 μM) decreased the amplitude of eIPSCs, suggesting that approximately 70% of the eIPSCs are generated by glycine. Moreover, blockade of GlyT2 partially diminished the glycinergic component of the light-evoked IPSCs. Using GlyT2ChR2/EYFP mice, we found that glycinergic fibers are abundant throughout the rostral brainstem, and GlyT2-expressing neurons were distributed within the ventral gigantocellular nucleus and medial reticular formation. Immunofluorescence labeling of glycine receptor subunits in the VLM/VMM revealed the expression of two prevalent forms of glycine receptors formed by α1 and α3. In summary, we found that GABA and glycine are co-released in the VLM/VMM, and blockage of GlyT2 decreased the amplitude of light-evoked IPSCs, suggesting that GABA and glycine are likely located in separate vesicles. Our data provide evidence for the co-inhibition of presympathetic neurons in the VLM/VMM by GABA and glycine and suggest that GABA controls the threshold excitability, while glycine is released on demand to increase the strength of inhibition. Supported by: NIDDK122842 and Tulane Brain Institute Marko Spark Innovation Research Fund This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Coordination of Locomotion by Serotonergic Neurons in the Predatory Gastropod Pleurobranchaea californica.

Similar design characterizes neuronal networks for goal-directed motor control across the complex, segmented vertebrates, insects, and polychaete annelids with jointed appendages. Evidence is lacking for whether this design evolved independently in those lineages, evolved in parallel with segmentation and appendages, or could have been present in a soft-bodied common ancestor. We examined coordination of locomotion in an unsegmented, ciliolocomoting gastropod, the sea slug Pleurobranchaea californica, which may better resemble the urbilaterian ancestor. Previously, bilateral A-cluster neurons in cerebral ganglion lobes were found to compose a multifunctional premotor network controlling the escape swim and feeding suppression, and mediating action selection for approach or avoidance turns. Serotonergic As interneurons of this cluster were critical elements for swimming, turning, and behavioral arousal. Here, known functions were extended to show that the As2/3 cells of the As group drove crawling locomotion via descending signals to pedal ganglia effector networks for ciliolocomotion and were inhibited during fictive feeding and withdrawal. Crawling was suppressed in aversive turns, defensive withdrawal, and active feeding, but not during stimulus-approach turns or prebite proboscis extension. Ciliary beating was not inhibited during escape swimming. These results show how locomotion is adaptively coordinated in tracking, handling, and consuming resources, and in defense. Taken with previous results, they also show that the A-cluster network acts similarly to the vertebrate reticular formation with its serotonergic raphe nuclei in facilitating locomotion, postural movements, and motor arousal. Thus, the general scheme controlling locomotion and posture might well have preceded the evolution of segmented bodies and articulated appendages.SIGNIFICANCE STATEMENT Similar design in the neuronal networks for goal-directed motor control is seen across the complex, segmented vertebrates, insects, and polychaete annelids with jointed appendages. Whether that design evolved independently or in parallel with complexity in body and behavior has been unanswered. Here it is shown that a simple sea slug, with primitive ciliary locomotion and lacking segmentation and appendages, has similar modular design in network coordination as vertebrates for posture in directional turns and withdrawal, locomotion, and general arousal. This suggests that a general neuroanatomical framework for the control of locomotion and posture could have arisen early during the evolution of bilaterians.

Contraversive Ocular Tilt Reaction, Body Lateropulsion and Gaze-Evoked Nystagmus After Inferior Cerebellar Peduncle and Dentate Nucleus Stroke

Contraversive Ocular Tilt Reaction, Body Lateropulsion and Gaze-Evoked Nystagmus After Inferior Cerebellar Peduncle and Dentate Nucleus Stroke

From one to many: Hypertonia in schizophrenia spectrum psychosis an integrative review and adversarial collaboration report

Different types of resistance to passive movement, i.e. hypertonia, were described in schizophrenia spectrum disorders (SSD) long before the introduction of antipsychotics. While these have been rediscovered in antipsychotic-naïve patients and their non-affected relatives, the existence of intrinsic hypertonia vs drug-induced parkinsonism (DIP) in treated SSD remains controversial. This integrative review seeks to develop a commonly accepted framework to specify the putative clinical phenomena, highlight conflicting issues and discuss ways to challenge each hypothesis and model through adversarial collaboration.The authors agreed on a common framework inspired from systems neuroscience. Specification of DIP, locomotor paratonia (LMP) and psychomotor paratonia (PMP) identified points of disagreement. Some viewed parkinsonian rigidity to be sufficient for diagnosing DIP, while others viewed DIP as a syndrome that should include bradykinesia. Sensitivity of DIP to anticholinergic drugs and the nature of LPM and PMP were the most debated issues.It was agreed that treated SSD should be investigated first. Clinical features of the phenomena at issue could be confirmed by torque, EMG and joint angle measures that could help in challenging the selectivity of DIP to anticholinergics. LMP was modeled as the release of the reticular formation from the control of the supplementary motor area (SMA), which could be challenged by the tonic vibration reflex or acoustic startle. PMP was modeled as the release of primary motor cortex from the control of the SMA and may be informed by subclinical echopraxia. If these challenges are not met, this would put new constraints on the models and have clinical and therapeutic implications.

Expression of SATB1 and SATB2 in the brain of bony fishes: what fish reveal about evolution

Satb1 and Satb2 belong to a family of homeodomain proteins with highly conserved functional and regulatory mechanisms and posttranslational modifications in evolution. However, although their distribution in the mouse brain has been analyzed, few data exist in other non-mammalian vertebrates. In the present study, we have analyzed in detail the sequence of SATB1 and SATB2 proteins and the immunolocalization of both, in combination with additional neuronal markers of highly conserved populations, in the brain of adult specimens of different bony fish models at key evolutionary points of vertebrate diversification, in particular including representative species of sarcopterygian and actinopterygian fishes. We observed a striking absence of both proteins in the pallial region of actinopterygians, only detected in lungfish, the only sarcopterygian fish. In the subpallium, including the amygdaloid complex, or comparable structures, we identified that the detected expressions of SATB1 and SATB2 have similar topologies in the studied models. In the caudal telencephalon, all models showed significant expression of SATB1 and SATB2 in the preoptic area, including the acroterminal domain of this region, where the cells were also dopaminergic. In the alar hypothalamus, all models showed SATB2 but not SATB1 in the subparaventricular area, whereas in the basal hypothalamus the cladistian species and the lungfish presented a SATB1 immunoreactive population in the tuberal hypothalamus, also labeled with SATB2 in the latter and colocalizing with the gen Orthopedia. In the diencephalon, all models, except the teleost fish, showed SATB1 in the prethalamus, thalamus and pretectum, whereas only lungfish showed also SATB2 in prethalamus and thalamus. At the midbrain level of actinopterygian fish, the optic tectum, the torus semicircularis and the tegmentum harbored populations of SATB1 cells, whereas lungfish housed SATB2 only in the torus and tegmentum. Similarly, the SATB1 expression in the rhombencephalic central gray and reticular formation was a common feature. The presence of SATB1 in the solitary tract nucleus is a peculiar feature only observed in non-teleost actinopterygian fishes. At these levels, none of the detected populations were catecholaminergic or serotonergic. In conclusion, the protein sequence analysis revealed a high degree of conservation of both proteins, especially in the functional domains, whereas the neuroanatomical pattern of SATB1 and SATB2 revealed significant differences between sarcopterygians and actinopterygians, and these divergences may be related to the different functional involvement of both in the acquisition of various neural phenotypes.

Dystonia-like behaviors and impaired sensory-motor integration following neurotoxic lesion of the pedunculopontine tegmental nucleus in mice.

The pedunculopontine nucleus (PPTg) is a vital interface between the basal ganglia and cerebellum, participating in modulation of the locomotion and muscle tone. Pathological changes of the PPTg have been reported in patients and animal models of dystonia, while its effect and mechanism on the phenotyping of dystonia is still unknown. In this study, a series of behavioral tests focusing on the specific deficits of dystonia were conducted for mice with bilateral and unilateral PPTg excitotoxic lesion, including the dystonia-like movements evaluation, different types of sensory-motor integrations, explorative behaviors and gait. In addition, neural dysfunctions including apoptosis, neuroinflammation, neurodegeneration and neural activation of PPTg-related motor areas in the basal ganglia, reticular formations and cerebellum were also explored. Both bilateral and unilateral lesion of the PPTg elicited dystonia-like behaviors featured by the hyperactivity of the hindlimb flexors. Moreover, proprioceptive and auditory sensory-motor integrations were impaired in bilaterally lesioned mice, while no overt alterations were found for the tactile sensory-motor integration, explorative behaviors and gait. Similar but milder behavioral deficits were found in the unilaterally lesioned mice, with an effective compensation was observed for the auditory sensory-motor integration. Histologically, no neural loss, apoptosis, neuroinflammation and neurodegeneration were found in the substantia nigra pars compacta and caudate putamen (CPu) following PPTg lesion, while reduced neural activity was found in the dorsolateral part of the CPu and striatal indirect pathway-related structures including subthalamic nucleus, globus pallidus internus and substantia nigra pars reticular. Moreover, the neural activity was decreased for the reticular formations such as pontine reticular nucleus, parvicellular reticular nucleus and gigantocellular reticular nucleus, while deep cerebellar nuclei were spared. In conclusion, lesion of the PPTg could elicit dystonia-like behaviors through its effect on the balance of the striatal pathways and the reticular formations.

Revisiting a Telencephalic Extent of the Ascending Reticular Activating System.

Is the cerebrum involved in its own activation to states of attention or arousal? "Telencephalon" is a term borrowed from embryology to identify not only the cerebral hemispheres of the forebrain, but also the basal forebrain. We review a generally undercited literature that describes nucleus basalis of Meynert, located within the substantia innominata of the ventrobasal forebrain, as a telencephalic extension of the ascending reticular activating formation. Although that formation's precise anatomical definition and localization have proven elusive over more than 70years, a careful reading of sources reveals that there are histological features common to certain brainstem neurons and those of the nucleus basalis, and that a largely common dendritic architecture may be a morphological aspect that helps to define non-telencephalic structures of the ascending reticular activating formation (e.g., in brainstem) as well as those parts of the formation that are telencephalic and themselves responsible for cortical activation. We draw attention to a pattern of dendritic arborization described as "isodendritic," a uniform (isos-) branching in which distal dendrite branches are significantly longer than proximal ones. Isodendritic neurons also differ from other morphological types based on their heterogeneous, rather than specific afferentation. References reviewed here are consistent in their descriptions of histology, particularly in studies of locales rich in cholinergic neurons. We discuss the therapeutic implications of a basal forebrain site that may activate cortex. Interventions that specifically target nucleus basalis and, especially, the survival of its constituent neurons may benefit afflictions in which higher cortical function is compromised due to disturbed arousal or attentiveness, including not only coma and related syndromes, but also conditions colloquially described as states of cognitive "fog" or of "long-haul" mental compromise.

Brain areas activated during visual learning in the cichlid fish Pseudotropheus zebra

The neural correlates of most cognitive functions in fish are unknown. This project aimed to identify brain regions involved in visual learning in the cichlid fish Pseudotropheus zebra. The expression of the protein pS6 was measured in 19 brain areas and compared between groups of individuals subjected to four different behavioral contexts (control, avoidance, trained, and novelty groups). Control group individuals were sacrificed with minimal interactions. Fish in the avoidance group were chased with a net for an hour, after which they were sacrificed. Individuals in the trained group received daily training sessions to associate a visual object with a food reward. They were sacrificed the day they reached learning criterion. Fish in the novelty group were habituated to one set of visual stimuli, then faced a change in stimulus type (novelty stimulus) before they were sacrificed. Fish in the three treatment groups showed the largest activation of pS6 in the inferior lobes and the tectum opticum compared to the control group. The avoidance group showed additional activation in the preoptic area, several telencephalic regions, the torus semicircularis, and the reticular formation. The trained group that received a food reward, showed additional activation of the torus lateralis, a tertiary gustatory center. The only area that showed strong activation in all three treatment groups was the nucleus diffusus situated within the inferior lobe. The inferior lobe receives prominent visual input from the tectum via the nucleus glomerulosus but so far, nothing is known about the functional details of this pathway. Our study showed for the first time that the inferior lobes play an important role in visual learning and object recognition.

Pons Lezyonlarının İki Nadir Prezentasyonu: Bir Buçuk Ve Sekiz Buçuk Sendromu

One-and-a-half syndrome refers to a unilateral lesion involving the ipsilateral medial longitudinal fascicle and the 6th cranial nevre nucleus and/or the paramedian pontine reticular formation. Eight-and-a-half syndrome is a syndrome in which one-and-a-half syndrome and ipsilateral 7th cranial nevre palsy are seen together. These rare conditions result from limited lesions of the pontine tegmentum. We presented two cases with one-and-a-half and eight-and-a-half syndromes with ischemic infarction and hemorrhage in pons, respectively.

Pairing Transcranial Magnetic Stimulation and Loud Sounds Produces Plastic Changes in Motor Output.

Most current methods for neuromodulation target the cortex. Approaches for inducing plasticity in subcortical motor pathways, such as the reticulospinal tract, could help to boost recovery after damage (e.g., stroke). In this study, we paired loud acoustic stimulation (LAS) with transcranial magnetic stimulation (TMS) over the motor cortex in male and female healthy humans. LAS activates the reticular formation; TMS activates descending systems, including corticoreticular fibers. Two hundred paired stimuli were used, with 50 ms interstimulus interval at which LAS suppresses TMS responses. Before and after stimulus pairing, responses in the contralateral biceps muscle to TMS alone were measured. Ten, 20, and 30 min after stimulus pairing ended, TMS responses were enhanced, indicating the induction of LTP. No long-term changes were seen in control experiments which used 200 unpaired TMS or LAS, indicating the importance of associative stimulation. Following paired stimulation, no changes were seen in responses to direct corticospinal stimulation at the level of the medulla, or in the extent of reaction time shortening by a loud sound (StartReact effect), suggesting that plasticity did not occur in corticospinal or reticulospinal synapses. Direct measurements in female monkeys undergoing a similar paired protocol revealed no enhancement of corticospinal volleys after paired stimulation, suggesting no changes occurred in intracortical connections. The most likely substrate for the plastic changes, consistent with all our measurements, is an increase in the efficacy of corticoreticular connections. This new protocol may find utility, as it seems to target different motor circuits compared with other available paradigms.SIGNIFICANCE STATEMENT Induction of plasticity by neurostimulation protocols may be promising to enhance functional recovery after damage such as following stroke, but current protocols mainly target cortical circuits. In this study, we developed a novel paradigm which may generate long-term changes in connections between cortex and brainstem. This could provide an additional tool to modulate and improve recovery.

Optical imaging of neurons related to fictive swallowing using GCaMP6f in an arterially perfused rat preparation

ObjectiveIt is difficult to comprehensively study the activity patterns and distribution of neurons in the brainstem that control the act of swallowing, as they are located deep in the brain. In this study, we aimed to evaluate the usefulness of calcium imaging using GCaMP6f in arterially perfused preparations to study the activity of swallowing-related neurons in the brainstem. MethodsArterially perfused rat preparations were prepared 3–4 weeks after the injection of a neuron-specific virus expressing GCaMP6f. Fictive swallowing was induced by repetitive electrical stimulation of the superior laryngeal nerve (SLN). Simultaneously, the activity of GCaMP6f-expressing neurons in the dorsal brainstem, between 0.1 and 4.8 mm rostral to the obex, was assessed by changes in the intracellular calcium concentration using confocal laser microscopy. ResultsNeurons responding to stimulation of the SLN included swallowing-related neurons (48%), which showed an increase in fluorescence intensity at the time of swallowing bursts in the cervical vagus nerve, and stimulation-related neurons (52%), which showed an increase in fluorescence intensity through stimulation, regardless of the swallowing bursts. Despite a broad search area, swallowing-related neurons were localized exclusively in and around the solitary nucleus. In contrast, most stimulation-related neurons were located in the brainstem reticular formation, which is more rostral than the solitary nucleus. ConclusionsCalcium imaging using GCaMP in arterially perfused rat preparations is useful for an efficient search of the activity pattern and distribution of neurons located in a wide area of the brainstem.

Immunohistochemical Localization of MD2, a Co-Receptor of TLR4, in the Adult Mouse Brain.

Myeloid differentiation factor 2 (MD2) is a co-receptor of a classical proinflammatory protein TLR4 whose activation leads to neuroinflammation. It is widely accepted that TLR4 is expressed on the cell surface of microglia and astrocytes, and MD2 is expected to be expressed by these cells as well. However, our previous study showed that neurons from certain nuclei also expressed MD2. Whether MD2 is expressed by other brain nuclei is still unknown. It is the aim of the present study to map the distribution of MD2-positive cells in the adult mouse brain. Immunohistochemical staining against MD2 was completed to localize MD2-positive cells in the mouse brain by comparing the location of positive cells with the mouse brain atlas. MD2-positive cells were found in the majority of mouse brain nuclei with clusters of cells in the olfactory bulb, cortices, the red nucleus, and cranial nuclei. Subcortical nuclei had heterogeneous staining of MD2 with more prominent cells in the basolateral and the central amygdaloid nuclei. The ventral pallidum and the diagonal bands had positive cells with similar density and shape. Prominent cells were present in thalamic nuclei which were nearly homogeneous and in reticular formation of the brainstem where cells were dispersed with similar density. The hypothalamus had fewer outstanding cells compared with the thalamus. The red nucleus, the substantia nigra, and the ventral tegmental area in the pretectum had outstanding cells. Motor cranial nuclei also had outstanding MD2-positive cells, whereas raphe, sensory cranial, and deep cerebellar nuclei had MD2-positive cells with moderate density. The presence of MD2 in these nuclei may suggest the involvement of MD2 in their corresponding physiological functions.

The Rostral Zona Incerta: A Subcortical Integrative Hub and Potential Deep Brain Stimulation Target for Obsessive-Compulsive Disorder

BackgroundThe zona incerta (ZI) is involved in mediating survival behaviors and is connected to a wide range of cortical and subcortical structures, including key basal ganglia nuclei. Based on these connections and their links to behavioral modulation, we propose that the ZI is a connectional hub for mediating between top-down and bottom-up control and a possible target for deep brain stimulation for obsessive-compulsive disorder. MethodsWe analyzed the trajectory of cortical fibers to the ZI in nonhuman and human primates based on tracer injections in monkeys and high-resolution diffusion magnetic resonance imaging in humans. The organization of cortical and subcortical connections within the ZI were identified in the nonhuman primate studies. ResultsMonkey anatomical data and human diffusion magnetic resonance imaging data showed a similar trajectory of fibers/streamlines to the ZI. Prefrontal cortex/anterior cingulate cortex terminals all converged within the rostral ZI, with dorsal and lateral areas being most prominent. Motor areas terminated caudally. Dense subcortical reciprocal connections included the thalamus, medial hypothalamus, substantia nigra/ventral tegmental area, reticular formation, and pedunculopontine nucleus and a dense nonreciprocal projection to the lateral habenula. Additional connections included the amygdala, dorsal raphe nucleus, and periaqueductal gray. ConclusionsDense connections with dorsal and lateral prefrontal cortex/anterior cingulate cortex cognitive control areas and the lateral habenula and the substantia nigra/ventral tegmental area, coupled with inputs from the amygdala, hypothalamus, and brainstem, suggest that the rostral ZI is a subcortical hub positioned to modulate between top-down and bottom-up control. A deep brain stimulation electrode placed in the rostral ZI would not only involve connections common to other deep brain stimulation sites but also capture several critically distinctive connections.

ИСПОЛЬЗОВАНИЕ ИНТЕГРАЛЬНЫХ ЛЕЙКОЦИТАРНЫХ ИНДЕКСОВ В ОЦЕНКЕ ВЛИЯНИЯ СТРЕССИРУЮЩИХ ФАКТОРОВ НА ГОМЕОСТАЗ КОЗ

The principle of a quantitative-qualitative approach, which reflects the activity of the organism while distinguishing its specific and non-specific adaptive responses, includes the requirement for quantitative assessment of specific changes in the body. To achieve the research objective, the resources of integral leukocyte indices (ILI) were used to assess the homeostasis of goats during castration, weaning from dams and transfer from pasture to stabling. After percutaneous castration, the index data vary significantly in a day, and in the month following the operation they slowly return to the level of the initial values. The surgical method of castration of goats acts as an unusual extreme stimulus, as it has a damaging effect on the body for a longer period of time. Changes in the blood of kids after weaning from dams were characterised by an increase in leukocytes by 36.84±2.71%, a change in the status of neutrophils, as they increased by 6.85±0.39%. The number of band immature neutrophils increased, but the presence of eosinophils decreased by 1.75±0.19 times, which is one of the indicators of the presence of a moderate stress factor. The transfer of goats to stabling leads to a sharp decrease in impulses from the skeletal muscles, which weakens the activating effect of the reticular formation of the brain on the cerebral cortex. The goat’s body is exposed to extreme stimuli, beyond the limits of everyday influences, and reacts specifically according to the nature of the activeagent. The most pronounced reaction is to open surgical castration, less so to percutaneous castration and then, in descending order: weaning of goats from dams and transfer from pasturing.

Changing a Reflex Motor Pattern Using the Allyane Technique: Case Report of a Dancer’s Chronic Ankle Instability

The treatment of chronic ankle instability (CAI) is quite long and problematic. In dance, about 53% of dancers have CAI. CAI is a major cause of musculoskeletal disorders such as sprains, posterior ankle impingement, and shin splints. Moreover, CAI leads to a loss of confidence and becomes a key factor for reducing or stopping dance. This case report assesses the effectiveness of the Allyane technique on CAI. Furthermore, it provides a better understanding of this pathology. The Allyane process is a neuromuscular reprogramming method based on the scientific background of neuroscience. Its aim is to strongly activate the afferent pathways of the reticular formation, responsible for voluntary motor learning. It uses mental skill imagery, afferent kinaesthetic sensations, and specific sequences of low-frequency sounds coming from a patented medical device. A. Is a 15-year-old female dancer who practices ballet 8 h per week. She has suffered from CAI for 3 years, with repeated sprains as well as a loss in confidence, with a direct implication on her career. Despite physiotherapy rehabilitation, her CAI tests were still deficient and she still felt strongly apprehensive while dancing. After 2 h of the Allyane technique, we notice a 195% gain of strength of the peroneus, 266% for the posterior tibialis, and 141% for the anterior tibialis muscles. Side hop test and the functional test (Cumberland Ankle Instability tool) normalized. 6 week later, the control assessment confirms this screening and gibes an idea of the durability of the technic. This neuroreprogramming method could not only open the door to interesting perspectives in the treatment of CAI, but it can also help in the understanding of this pathology in case of central muscle inhibitions.

The role of neurotransmitters and indicators of oxidative stress in the formation of disorders of central conductive structures in patients who came into contact with metallic mercury

Introduction. Studies of toxic lesions due to exposure to metallic mercury compounds do not allow us to identify the features of the violation of central afferent conducting structures in the long-term period of chronic mercury intoxication (CHMI). The contribution of various systems to the development of pathology is not sufficiently disclosed. The study aims to identify the role of neurotransmitters in pathological changes in central hemodynamics, the value of lipid peroxidation products and the activity of antioxidant protection in the demyelination of central afferent conductive structures in workers exposed to metallic mercury in the workplace. Materials and methods. The authors examined 47 people (group one) - trained chemical production workers exposed to metallic mercury, and group two (51 people) - patients in the long-term period of CHMI. The control group (CG) consisted of 30 people who had no contact with toxicants. We have determined concentration of neurotransmitters, lipid peroxidation products (LPP), superoxide dismutase (SOD) and reduced glutathione (RG), nitric oxide. Results. Experts observed statistically significant changes in indicators in subgroups with and without changes in cerebral hemodynamics and in group two when compared with group one. Comparison of persons with CHMI without changes in blood circulation with the presence of disorders revealed an increase in normetanephrine in the latter, a decrease in NT-3. Correlation analysis showed: in group jne, there was a statistically significant difference between the vasomotor reactivity index (VRI) and serotonin. In group two - between CHMI and serotonin, adrenaline and dopamine. Changes in afferent pathways are interrelated with indicators of oxidative stress. Violations are accompanied by the formation of a pathological system, are signs of dysregulatory pathology. Limitations. The disadvantage of the study is the fact that scientists determined the content of neurotransmitters and products of lipid peroxidation and antioxidant protection in the blood of the subjects, and not in the structures of the brain. Conclusion. The increased content of biogenic amines leads to a change in peripheral blood circulation and regulation of cerebral blood flow by pressor action on the regulation of the vascular bed, leading to vasoconstriction, changes in the bioelectric activity of the structures of the reticular formation of the midbrain, hypothalamus, thalamocortical structures, most pronounced in the long-term period of chronic mercury intoxication. We found that the formation of demyelination in patients with chronic mercury intoxication was accompanied by a decrease in the concentration of NT-3. It was natural to reduce the level of reduced glutathione and superoxide dismutase in neurodegenerative processes in trained workers exposed to metallic mercury at work, and in patients with a long period of chronic mercury intoxication. Ethics. The study was conducted in compliance with the principles of the Helsinki Declaration of the World Association "Ethical principles of conducting Scientific medical research with human participation" (as amended in 2008), "Rules of Clinical Practice in the Russian Federation" (approved by the Order of the Ministry of Health of the Russian Federation dated 06/19/2003 No. 266).

Cerebellar Inputs in the American Alligator (Alligator mississippiensis)

Crocodilians (alligators, crocodiles, and gharials) are the closet living relatives to birds and, as such, represent a key clade to understand the evolution of the avian brain. However, many aspects of crocodilian neurobiology remain unknown. In this paper, we address an important knowledge gap as there are no published studies of cerebellar connections in any crocodilian species. We used injections of retrograde tracers into the cerebellum of the American alligator (Alligator mississippiensis) to describe for the first time the origin of climbing and mossy fiber inputs. We found that inputs to the cerebellum in the American alligator are similar to those of other nonavian reptiles and birds. Retrograde labeled cells were found in the spinal cord, inferior olive, reticular formation, vestibular and cerebellar nuclei, as well as in nucleus ruber and surrounding tegmentum. Additionally, we found no retrogradely labeled cells in the anterior rhombencephalon which suggest that, like other nonavian reptiles, crocodilians may lack pontine nuclei. Similar to birds and other nonavian reptiles, we found inputs to the cerebellum from the pretectal nucleus lentiformis mesencephali. Additionally, we found retrogradely labeled neurons in two nuclei in the pretectum: the nucleus circularis and the interstitial nucleus of the posterior commissure. These pretectal projections have not been described in any other nonavian reptile to date, but they do resemble projections from the nucleus spiriformis medialis of birds. Our results show that many inputs to the cerebellum are highly conserved among sauropsids and that extensive pretectal inputs to the cerebellum are not exclusive to the avian brain. Finally, we suggest that the pontine nuclei of birds are an evolutionary novelty that may have evolved after the last common ancestor between birds and crocodilians, and may represent an intriguing case of convergent evolution with mammals.

Role of Cervical Spinal Magnetic Stimulation in Improving Posture and Functional Ambulation of Patients with Relapsing Remitting Multiple Sclerosis.

Balance impairment is one of the hallmarks of early MS. Proprioceptive deficit was found to be one of the main causes of this imbalance. The cervical enlargement has a strong proprioceptive system, with its projections to the reticular formation and the central pattern generators, helping in rhythmic pattern generation and alternate leg movements. Repetitive trans-spinal magnetic stimulation (rTSMS) is a noninvasive technique, which can trigger massive proprioceptive afferents. Therefore, it has the potential of improving proprioceptive deficits and motor control. Objective. To determine the effectiveness of repetitive cervical magnetic stimulation in improving functional ambulation of patients with relapsing remitting multiple sclerosis (RRMS). Design. Prospective sequential clinical trial. Setting. University and academic hospital. Participants. A total of 32 participants (N = 32) with RRMS. Interventions. Outpatient rehabilitation. The 32 patients received 10 sessions over two weeks of 20 Hz cervical spinal magnetic stimulation (SMS). Both groups were assessed at baseline, after 2 weeks, then one month later. Patients were enrolled as a control group at first and received Sham SMS, and then a wash out period of one month was done for all the patients, followed by a baseline assessment. Second, the same 32 patients rejoined as the active group, which received real magnetic stimulation. Both groups performed an intensive physical therapy program with the spinal magnetic stimulation. Main Outcome Measures. Extended Disability status score (EDSS), Timed up and Go test (TUG), Mini-Best test, dynamic posturography sensory organization composite score, and motor composite score. Results. Thirty-two RRMS patients with EDSS range from 1.5 to 6. They showed statistically significant difference between active and control groups in Mini-Best test score. We divided our patients according to EDSS into 3 subgroups: (a) mild: ≤2.5, (b) moderate: 3-5.5, and (c) severe: ≥6. Mild cases showed significant differences in EDSS score, TUG test, Mini-Best test, and dynamic posturography sensory composite scale. The effect size between the different patient subgroups was also measured and showed highly significant improvements in all measured parameters among our mild patients, indicating that this subgroup could be the best responders to cervical repetitive high-frequency magnetic stimulation. Moderate cases showed highly significant improvement in TUG score and Mini-Best test and significant change in EDSS score and the dynamic posturography sensory composite score. Severe cases showed only significant improvements in TUG, Mini-Best test, and sensory composite score. Conclusion. Cervical repetitive magnetic stimulation can help improve balance and functional ambulation and decreases the risk of falls in RRMS patients, especially in the mild, low disability cases.

Organization of serotonergic system in Sphaerotheca breviceps (Dicroglossidae) tadpole brain.

The monoaminergic neurotransmitter 5-hydroxytryptamine (5-HT) is known to be involved in several physiological, behavioural and neuroendocrine functions in vertebrates. In this study, we investigated the distribution of 5-HT neuronal system in the central nervous system (CNS) of Sphaerotheca breviceps tadpoles at metamorphic climax stage. In the telencephalon, there was no 5-HT-immunoreactive (5-HT-ir) perikarya, but conspicuous fibres were observed in the olfactory bulb, pallium, subpallium and amygdala complexes. The preoptic area showed dense 5-HT-ir somata and cerebrospinal fluid contacting fibres, whereas a few varicose 5-HT-ir fibres were noticed in the suprachiasmatic nucleus. 5-HT-ir cells and fibres were found in the ventral, lateral dorsal subdivisions of the hypothalamus and in the nucleus tuberculi posterioris, but only 5-HT-ir fibres were localised in the periventricular area and pituitary gland. Numerous 5-HT-ir cells and/or fibres were detected in the thalamus, entopeduncular area and mesencephalic subdivisions. In the rhombencephalon, although 5-HT-ir cells and fibres were noticed in the subdivisions of the raphe nucleus and reticular formation, a moderate plexus of fibres was observed in the cerebellum, parabrachial nucleus and solitary tract. Distinct 5-HT-ir fibres, but no perikarya, were observed in the rostral spinal cord. Overall, extensively labelled 5-HT-ir cells and fibres in the CNS of the metamorphic tadpole suggest possible roles for the involvement of 5-HT in various somatosensory, behavioural and neuroendocrine functions during final stages of development.