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1.
Artigo em Russo | MEDLINE | ID: mdl-34693698

RESUMO

Exploding head syndrome (EHS) is a paroxysmal sensory parasomnia characterized by the sensation of a loud noise or «explosion in the head¼ during the wake-sleep/sleep-wake cycle. The most popular explanation for this condition is the decrease of reticular formation activity during the transition between wakefulness and sleep. The authors present a review of literature on the diagnosis and treatment of EHS and clinical observations of patients with classical signs.


Assuntos
Parassonias , Transtornos do Sono-Vigília , Humanos , Parassonias/diagnóstico , Formação Reticular , Sono , Vigília
2.
Int J Mol Sci ; 22(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34445628

RESUMO

We investigated the alterations of hippocampal and reticulo-thalamic (RT) GABAergic parvalbumin (PV) interneurons and their synaptic re-organizations underlying the prodromal local sleep disorders in the distinct rat models of Parkinson's disease (PD). We demonstrated for the first time that REM sleep is a predisposing state for the high-voltage sleep spindles (HVS) induction in all experimental models of PD, particularly during hippocampal REM sleep in the hemiparkinsonian models. There were the opposite underlying alterations of the hippocampal and RT GABAergic PV+ interneurons along with the distinct MAP2 and PSD-95 expressions. Whereas the PD cholinopathy enhanced the number of PV+ interneurons and suppressed the MAP2/PSD-95 expression, the hemiparkinsonism with PD cholinopathy reduced the number of PV+ interneurons and enhanced the MAP2/PSD-95 expression in the hippocampus. Whereas the PD cholinopathy did not alter PV+ interneurons but partially enhanced MAP2 and suppressed PSD-95 expression remotely in the RT, the hemiparkinsonism with PD cholinopathy reduced the PV+ interneurons, enhanced MAP2, and did not change PSD-95 expression remotely in the RT. Our study demonstrates for the first time an important regulatory role of the hippocampal and RT GABAergic PV+ interneurons and the synaptic protein dynamic alterations in the distinct rat models of PD neuropathology.


Assuntos
Modelos Animais de Doenças , Hipocampo/patologia , Interneurônios/patologia , Doença de Parkinson/complicações , Parvalbuminas/metabolismo , Transtornos do Sono-Vigília/patologia , Sinapses/patologia , Animais , Proteína 4 Homóloga a Disks-Large/genética , Proteína 4 Homóloga a Disks-Large/metabolismo , Hipocampo/metabolismo , Interneurônios/metabolismo , Masculino , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Neuropatologia , Ratos , Ratos Wistar , Formação Reticular/metabolismo , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/metabolismo , Sinapses/metabolismo , Tálamo/metabolismo , Ácido gama-Aminobutírico/metabolismo
3.
Medicine (Baltimore) ; 100(9): e23933, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33655907

RESUMO

ABSTRACT: We report on a patient with hypoxic-ischemic brain injury (HI-BI) who showed recovery from a minimally consciousness state over 6 years concurrent with recovery of an injured ascending reticular activating system (ARAS), which was demonstrated on diffusion tensor tractography (DTT).A 31-year-old female patient, who suffered from HI-BI, showed impaired consciousness with a minimally conscious state: intermittently obeying simple motor tasks, such as "please grasp my hand." Her consciousness showed recovery with the passage of time; rapid recovery was observed during the recent 2 years.In the upper ARAS, the neural connectivity to both the basal forebrain and prefrontal cortex had increased on 8-year DTT compared with 1.5-year DTT. In the lower dorsal and ventral ARAS, no significant change was observed between 1.5 and 8 years DTTs.Recovery of an injured ARAS was demonstrated in a patient who showed recovery from a minimally consciousness state over 6 years following HI-BI. Our results suggest the brain target areas for recovery of impaired awareness in patients with disorders of consciousness.


Assuntos
Imagem de Tensor de Difusão , Hipóxia-Isquemia Encefálica/fisiopatologia , Estado Vegetativo Persistente/fisiopatologia , Recuperação de Função Fisiológica , Formação Reticular/lesões , Adulto , Feminino , Humanos , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Estado Vegetativo Persistente/diagnóstico por imagem , Estado Vegetativo Persistente/etiologia , Formação Reticular/diagnóstico por imagem , Formação Reticular/fisiopatologia
4.
J Neurophysiol ; 125(4): 993-1005, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33566745

RESUMO

Swallow is a primitive behavior regulated by medullary networks, responsible for movement of food/liquid from the oral cavity to the esophagus. To investigate how functionally heterogeneous networks along the medullary intermediate reticular formation (IRt) and ventral respiratory column (VRC) control swallow, we electrically stimulated the nucleus tractus solitarius to induce fictive swallow between inspiratory bursts, with concurrent optical recordings using a synthetic Ca2+ indicator in the neonatal sagittally sectioned rat hindbrain (SSRH) preparation. Simultaneous recordings from hypoglossal nerve rootlet (XIIn) and ventral cervical spinal root C1-C2 enabled identification of the system-level correlates of 1) swallow (identified as activation of the XIIn but not the cervical root) and 2) Breuer-Hering expiratory reflex (BHE; lengthened expiration in response to stimuli during expiration). Optical recording revealed reconfiguration of respiration-modulated networks in the ventrolateral medulla during swallow and the BHE reflex. Recordings identified novel spatially compact networks in the IRt near the facial nucleus (VIIn) that were active during fictive swallow, suggesting that the swallow network is not restricted to the caudal medulla. These findings also establish the utility of using this in vitro preparation to investigate how functionally heterogeneous medullary networks interact and reconfigure to enable a repertoire of orofacial behaviors.NEW & NOTEWORTHY For the first time, medullary networks that control breathing and swallow are recorded optically. Episodic swallows are induced via electrical stimulation along the dorsal medulla, in and near the NTS, during spontaneously occurring fictive respiration. These findings establish that networks regulating both orofacial behaviors and breathing are accessible for optical recording at the surface of the sagittally sectioned rodent hindbrain preparation.


Assuntos
Geradores de Padrão Central/fisiologia , Deglutição/fisiologia , Respiração , Formação Reticular/fisiologia , Rombencéfalo/fisiologia , Animais , Animais Recém-Nascidos , Estimulação Elétrica , Bulbo/fisiologia , Imagem Óptica , Ratos , Ratos Sprague-Dawley
5.
J Neurosci ; 41(5): 1005-1018, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33268548

RESUMO

Early evolution of the motor cortex included development of connections to brainstem reticulospinal neurons; these projections persist in primates. In this study, we examined the organization of corticoreticular connections in five macaque monkeys (one male) using both intracellular and extracellular recordings from reticular formation neurons, including identified reticulospinal cells. Synaptic responses to stimulation of different parts of primary motor cortex (M1) and supplementary motor area (SMA) bilaterally were assessed. Widespread short latency excitation, compatible with monosynaptic transmission over fast-conducting pathways, was observed, as well as longer latency responses likely reflecting a mixture of slower monosynaptic and oligosynaptic pathways. There was a high degree of convergence: 56% of reticulospinal cells with input from M1 received projections from M1 in both hemispheres; for SMA, the equivalent figure was even higher (70%). Of reticulospinal neurons with input from the cortex, 78% received projections from both M1 and SMA (regardless of hemisphere); 83% of reticulospinal cells with input from M1 received projections from more than one of the tested M1 sites. This convergence at the single cell level allows reticulospinal neurons to integrate information from across the motor areas of the cortex, taking account of the bilateral motor context. Reticulospinal connections are known to strengthen following damage to the corticospinal tract, such as after stroke, partially contributing to functional recovery. Extensive corticoreticular convergence provides redundancy of control, which may allow the cortex to continue to exploit this descending pathway even after damage to one area.SIGNIFICANCE STATEMENT The reticulospinal tract (RST) provides a parallel pathway for motor control in primates, alongside the more sophisticated corticospinal system. We found extensive convergent inputs to primate reticulospinal cells from primary and supplementary motor cortex bilaterally. These redundant connections could maintain transmission of voluntary commands to the spinal cord after damage (e.g., after stroke or spinal cord injury), possibly assisting recovery of function.


Assuntos
Córtex Motor/fisiologia , Neurônios/fisiologia , Tratos Piramidais/fisiologia , Formação Reticular/fisiologia , Medula Espinal/fisiologia , Animais , Potenciais Pós-Sinápticos Excitadores/fisiologia , Feminino , Macaca mulatta , Masculino , Potenciais da Membrana/fisiologia , Vias Neurais/fisiologia
6.
Curr Biol ; 30(23): 4665-4681.e6, 2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-33007251

RESUMO

Spatial orientation requires the execution of lateralized movements and a change in the animal's heading in response to multiple sensory modalities. While much research has focused on the circuits for sensory integration, chiefly to the midbrain superior colliculus (SC), the downstream cells and circuits that engage adequate motor actions have remained elusive. Furthermore, the mechanisms supporting trajectory changes are still speculative. Here, using transneuronal viral tracings in mice, we show that brainstem V2a neurons, a genetically defined subtype of glutamatergic neurons of the reticular formation, receive putative synaptic inputs from the contralateral SC. This makes them a candidate relay of lateralized orienting commands. We next show that unilateral optogenetic activations of brainstem V2a neurons in vivo evoked ipsilateral orienting-like responses of the head and the nose tip on stationary mice. When animals are walking, similar stimulations impose a transient locomotor arrest followed by a change of trajectory. Third, we reveal that these distinct motor actions are controlled by dedicated V2a subsets each projecting to a specific spinal cord segment, with at least (1) a lumbar-projecting subset whose unilateral activation specifically controls locomotor speed but neither impacts trajectory nor evokes orienting movements, and (2) a cervical-projecting subset dedicated to head orientation, but not to locomotor speed. Activating the latter subset suffices to steer the animals' directional heading, placing the head orientation as the prime driver of locomotor trajectory. V2a neurons and their modular organization may therefore underlie the orchestration of multiple motor actions during multi-faceted orienting behaviors.


Assuntos
Locomoção/fisiologia , Neurônios/fisiologia , Orientação Espacial/fisiologia , Formação Reticular/fisiologia , Colículos Superiores/fisiologia , Animais , Vértebras Cervicais , Feminino , Ácido Glutâmico/metabolismo , Proteínas de Homeodomínio/genética , Vértebras Lombares , Masculino , Camundongos , Camundongos Transgênicos , Modelos Animais , Vias Neurais/fisiologia , Optogenética , Formação Reticular/citologia , Medula Espinal/citologia , Medula Espinal/fisiologia , Colículos Superiores/citologia , Fatores de Transcrição/genética
7.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2889-2892, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018610

RESUMO

Understanding the fundamental roles of brainstem function resulting in proper motor control is critical to motor-rehabilitation after brain injuries. In particular, vestibular and reticular formation nuclei are thought to be associated with spasticity in chronic stroke patients. We used two kinds of stimuli in 10 healthy subjects to activate these nuclei while collecting high-resolution (1.5-mm) fMRI across the majority of brainstem. Optokinetic stimuli evoked illusory self-motion to activate the vestibular nuclei. Acoustic-startle stimuli were sets of loud tones designed to activate of the reticular formation. We summarized the response represented in a form of activation volume, mean percent signal change, and the phase delay (time lag) following the stimulus. We observed patterns of significant activations in the brainstem but did not find significant differences between the stimulus. We conclude that more sensitive measurement techniques are needed to reliably detect vestibular and reticular formation nuclei responses.


Assuntos
Formação Reticular , Núcleos Vestibulares , Estimulação Acústica , Acústica , Humanos , Imageamento por Ressonância Magnética
8.
J Neurosci ; 40(44): 8478-8490, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-32998974

RESUMO

Meso-diencephalic dopaminergic neurons are known to modulate locomotor behaviors through their ascending projections to the basal ganglia, which in turn project to the mesencephalic locomotor region, known to control locomotion in vertebrates. In addition to their ascending projections, dopaminergic neurons were found to increase locomotor movements through direct descending projections to the mesencephalic locomotor region and spinal cord. Intriguingly, fibers expressing tyrosine hydroxylase (TH), the rate-limiting enzyme of dopamine synthesis, were also observed around reticulospinal neurons of lampreys. We now examined the origin and the role of this innervation. Using immunofluorescence and tracing experiments, we found that fibers positive for dopamine innervate reticulospinal neurons in the four reticular nuclei of lampreys. We identified the dopaminergic source using tracer injections in reticular nuclei, which retrogradely labeled dopaminergic neurons in a caudal diencephalic nucleus (posterior tuberculum [PT]). Using voltammetry in brain preparations isolated in vitro, we found that PT stimulation evoked dopamine release in all four reticular nuclei, but not in the spinal cord. In semi-intact preparations where the brain is accessible and the body moves, PT stimulation evoked swimming, and injection of a D1 receptor antagonist within the middle rhombencephalic reticular nucleus was sufficient to decrease reticulospinal activity and PT-evoked swimming. Our study reveals that dopaminergic neurons have access to command neurons that integrate sensory and descending inputs to activate spinal locomotor neurons. As such, our findings strengthen the idea that dopamine can modulate locomotor behavior both via ascending projections to the basal ganglia and through descending projections to brainstem motor circuits.SIGNIFICANCE STATEMENT Meso-diencephalic dopaminergic neurons play a key role in modulating locomotion by releasing dopamine in the basal ganglia, spinal networks, and the mesencephalic locomotor region, a brainstem region that controls locomotion in a graded fashion. Here, we report in lampreys that dopaminergic neurons release dopamine in the four reticular nuclei where reticulospinal neurons are located. Reticulospinal neurons integrate sensory and descending suprareticular inputs to control spinal interneurons and motoneurons. By directly modulating the activity of reticulospinal neurons, meso-diencephalic dopaminergic neurons control the very last instructions sent by the brain to spinal locomotor circuits. Our study reports on a new direct descending dopaminergic projection to reticulospinal neurons that modulates locomotor behavior.


Assuntos
Neurônios Dopaminérgicos/fisiologia , Locomoção/fisiologia , Formação Reticular/fisiologia , Medula Espinal/fisiologia , Animais , Fenômenos Biomecânicos , Antagonistas de Dopamina/farmacologia , Estimulação Elétrica , Fenômenos Eletrofisiológicos , Lampreias , Fibras Nervosas/fisiologia , Receptores de Dopamina D1/antagonistas & inibidores , Natação , Tirosina 3-Mono-Oxigenase/fisiologia
9.
Acta Neurol Taiwan ; 29(3): 86-89, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32996116

RESUMO

PURPOSE: Focal signs are a big deal in neurology and are among the most important clues leading to diagnosis and localization. Wernekink commissure syndrome is due to lesions in the caudal paramedian midbrain involving the entire decussation of the superior cerebellar peduncles, resulting in the clinical hallmark of a bilateral cerebellar syndrome. CASE REPORT: A 79-year-old man presented with sudden, severe unsteadiness associated with slurring of speech, binocular double vision, and bilateral hand tremor. Examination showed right INO, moderately severe dysarthria, bilateral dysmetria and dysdiadochokinesia, with severe truncal ataxia and bilateral upper and lower limb ataxia. Also, bilateral coarse tremor was noted in both hands which was present at rest, action and on reaching for objects. Brain MRI revealed an acute infarction involving the Wernekinck decussation in the right caudal midbrain and mesencephalo-pontine junction. CONCLUSION: The differential of Wernekink Commissure Syndrome is complex, and localization and lateralization are extremely difficult owing to prominent bilateral cerebellar symptoms. The finding of an associated unilateral INO in some cases makes it possible to confidently narrow the list of differentials and localize the lesion to the paramedian tegmentum ipsilateral to the non-adducting eye.


Assuntos
Ataxia Cerebelar/etiologia , Doenças Cerebelares , Infarto Cerebral/complicações , Mesencéfalo/diagnóstico por imagem , Tegmento Mesencefálico/irrigação sanguínea , Idoso , Doenças Cerebelares/diagnóstico por imagem , Doenças Cerebelares/etiologia , Infarto Cerebral/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtornos da Motilidade Ocular/etiologia , Formação Reticular/patologia , Síndrome
10.
J Neurosci ; 40(43): 8292-8305, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-32978289

RESUMO

Traditionally, the brainstem has been seen as hardwired and poorly capable of plastic adaptations following spinal cord injury (SCI). Data acquired over the past decades, however, suggest differently: following SCI in various animal models (lamprey, chick, rodents, nonhuman primates), different forms of spontaneous anatomic plasticity of reticulospinal projections, many of them originating from the gigantocellular reticular nucleus (NRG), have been observed. In line with these anatomic observations, animals and humans with incomplete SCI often show various degrees of spontaneous motor recovery of hindlimb/leg function. Here, we investigated the functional relevance of two different modes of reticulospinal fiber growth after cervical hemisection, local rewiring of axotomized projections at the lesion site versus compensatory outgrowth of spared axons, using projection-specific, adeno-associated virus-mediated chemogenetic neuronal silencing. Detailed assessment of joint movements and limb kinetics during overground locomotion in female adult rats showed that locally rewired as well as compensatory NRG fibers were responsible for different aspects of recovered forelimb and hindlimb functions (i.e., stability, strength, coordination, speed, or timing). During walking and swimming, both locally rewired as well as compensatory NRG plasticity were crucial for recovered function, while the contribution of locally rewired NRG plasticity to wading performance was limited. Our data demonstrate comprehensively that locally rewired as well as compensatory plasticity of reticulospinal axons functionally contribute to the observed spontaneous improvement of stepping performance after incomplete SCI and are at least partially causative to the observed recovery of function, which can also be observed in human patients with spinal hemisection lesions.SIGNIFICANCE STATEMENT Following unilateral hemisection of the spinal cord, reticulospinal projections are destroyed on the injured side, resulting in impaired locomotion. Over time, a high degree of recovery can be observed in lesioned animals, like in human hemicord patients. In the rat, recovery is accompanied by pronounced spontaneous plasticity of axotomized and spared reticulospinal axons. We demonstrate the causative relevance of locally rewired as well as compensatory reticulospinal plasticity for the recovery of locomotor functions following spinal hemisection, using chemogenetic tools to selectively silence newly formed connections in behaviorally recovered animals. Moving from a correlative to a causative understanding of the role of neuroanatomical plasticity for functional recovery is fundamental for successful translation of treatment approaches from experimental studies to the clinics.


Assuntos
Locomoção , Formação Reticular/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Animais , Axônios , Axotomia , Fenômenos Biomecânicos , Feminino , Membro Anterior/fisiopatologia , Membro Posterior/fisiopatologia , Fibras Nervosas , Regeneração Nervosa , Plasticidade Neuronal , Ratos , Ratos Endogâmicos Lew , Recuperação de Função Fisiológica , Natação , Caminhada
11.
J Neurosci ; 40(46): 8831-8841, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-32883710

RESUMO

Humans with cervical spinal cord injury (SCI) often recover voluntary control of elbow flexors and, to a much lesser extent, elbow extensor muscles. The neural mechanisms underlying this asymmetrical recovery remain unknown. Anatomical and physiological evidence in animals and humans indicates that corticospinal and reticulospinal pathways differentially control elbow flexor and extensor motoneurons; therefore, it is possible that reorganization in these pathways contributes to the asymmetrical recovery of elbow muscles after SCI. To test this hypothesis, we examined motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation over the arm representation of the primary motor cortex, maximal voluntary contractions, the StartReact response (a shortening in reaction time evoked by a startling stimulus), and the effect of an acoustic startle cue on MEPs elicited by cervicomedullary stimulation (CMEPs) on biceps and triceps brachii in males and females with and without chronic cervical incomplete SCI. We found that SCI participants showed similar MEPs and maximal voluntary contractions in biceps but smaller responses in triceps compared with controls, suggesting reduced corticospinal inputs to elbow extensors. The StartReact and CMEP facilitation was larger in biceps but similar to controls in triceps, suggesting enhanced reticulospinal inputs to elbow flexors. These findings support the hypothesis that the recovery of biceps after cervical SCI results, at least in part, from increased reticulospinal inputs and that the lack of these extra inputs combined with the loss of corticospinal drive contribute to the pronounced weakness found in triceps.SIGNIFICANCE STATEMENT Although a number of individuals with cervical incomplete spinal cord injury show limited functional recovery of elbow extensors compared with elbow flexor muscles, to date, the neural mechanisms underlying this asymmetrical recovery remain unknown. Here, we provide for the first time evidence for increased reticulospinal inputs to biceps but not triceps brachii and loss of corticospinal drive to triceps brachii in humans with tetraplegia. We propose that this reorganization in descending control contributes to the asymmetrical recovery between elbow flexor and extensor muscles after cervical spinal cord injury.


Assuntos
Cotovelo/fisiopatologia , Músculo Esquelético/fisiopatologia , Tratos Piramidais/fisiopatologia , Quadriplegia/fisiopatologia , Formação Reticular/fisiopatologia , Adulto , Idoso , Sinais (Psicologia) , Eletromiografia , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor , Contração Muscular/fisiologia , Recrutamento Neurofisiológico , Reflexo de Sobressalto , Traumatismos da Medula Espinal/fisiopatologia , Estimulação Magnética Transcraniana , Adulto Jovem
12.
Neurosci Lett ; 738: 135400, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32979458

RESUMO

The interneuronal system in the brainstem reticular formation plays an important role in elaborate muscle coordination during various orofacial motor behaviors. In this study, we examined the distribution in the brainstem reticular formation of the sites that induce monosynaptic motor activity in the mylohyoid (jaw-opening) and hypoglossal nerves using an arterially perfused rat preparation. Electrical stimulation applied to 286 and 247 of the 309 sites in the brainstem evoked neural activity in the mylohyoid and hypoglossal nerves, respectively. The mean latency of the first component in the mylohyoid nerve response was significantly shorter than that in the hypoglossal nerve response. Moreover, the latency histogram of the first component in the hypoglossal nerve responses was bimodal, which was separated by 4.0 ms. The sites that induced short-latency (<4.0 ms) motor activity in the mylohyoid nerve and the hypoglossal nerve were frequently distributed in the rostral portion and the caudal portion of the brainstem reticular formation, respectively. Such difference in distributions of short-latency sites for mylohyoid and hypoglossal nerve responses likely corresponds to the distribution of excitatory premotor neurons targeting mylohyoid and hypoglossal motoneurons.


Assuntos
Tronco Encefálico/fisiologia , Estimulação Elétrica , Nervo Hipoglosso/patologia , Nervo Hipoglosso/fisiologia , Formação Reticular/fisiologia , Animais , Tronco Encefálico/patologia , Estimulação Elétrica/métodos , Eletromiografia/métodos , Neurônios Motores/fisiologia , Ratos , Formação Reticular/patologia , Núcleos do Trigêmeo/patologia , Núcleos do Trigêmeo/fisiologia
13.
J Neurosci ; 40(37): 7091-7104, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32801149

RESUMO

Skilled forelimb movements are initiated by feedforward motor commands conveyed by supraspinal motor pathways. The accuracy of reaching and grasping relies on internal feedback pathways that update ongoing motor commands. In mice lacking the axon guidance molecule EphA4, axonal misrouting of the corticospinal tract and spinal interneurons is manifested, leading to a hopping gait in hindlimbs. Moreover, mice with a conditional forebrain deletion of EphA4, display forelimb hopping in adaptive locomotion and exploratory reaching movements. However, it remains unclear how loss of EphA4 signaling disrupts function of forelimb motor circuit and skilled reaching and grasping movements. Here we investigated how neural circuits controlling skilled reaching were affected by the loss of EphA4. Both male and female C57BL/6 wild-type, heterozygous EphA4+/-, and homozygous EphA4-/- mice were used in behavioral and in vivo electrophysiological investigations. We found that EphA4 knock-out (-/-) mice displayed impaired goal-directed reaching movements. In vivo intracellular recordings from forelimb motor neurons demonstrated increased corticoreticulospinal excitation, decreased direct reticulospinal excitation, and reduced direct propriospinal excitation in EphA4 knock-out mice. Cerebellar surface recordings showed a functional perturbation of the lateral reticular nucleus-cerebellum internal feedback pathway in EphA4 knock-out mice. Together, our findings provide in vivo evidence at the circuit level that loss of EphA4 disrupts the function of both feedforward and feedback motor pathways, resulting in deficits in skilled reaching.SIGNIFICANCE STATEMENT The central advances of this study are the demonstration that null mutation in the axon guidance molecule EphA4 gene impairs the ability of mice to perform skilled reaching, and identification of how these behavioral deficits correlates with discrete neurophysiological changes in central motor pathways involved in the control of reaching. Our findings provide in vivo evidence at the circuit level that loss of EphA4 disrupts both feedforward and feedback motor pathways, resulting in deficits in skilled reaching. This analysis of motor circuit function may help to understand the pathophysiological mechanisms underlying movement disorders in humans.


Assuntos
Força da Mão , Destreza Motora , Tratos Piramidais/metabolismo , Receptor EphA4/metabolismo , Formação Reticular/metabolismo , Animais , Cerebelo/metabolismo , Cerebelo/fisiologia , Retroalimentação Fisiológica , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios Motores/metabolismo , Neurônios Motores/fisiologia , Tratos Piramidais/fisiologia , Receptor EphA4/genética , Formação Reticular/fisiologia
14.
Brain Res Bull ; 162: 94-106, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32562720

RESUMO

Vesicular glutamate transporter (VGLUT) 1 and VGLUT2 have been reported to distribute complementally in most brain regions and have been assumed to define distinct functional elements. Previous studies have shown the expression of VGLUT1 mRNA and VGLUT2 mRNA in the lateral reticular nucleus (LRN), a key precerebellar nucleus sending mossy fibers to the cerebellum. In the present study, we firstly examined the coexpression of VGLUT1 and VGLUT2 mRNA in the LRN of the rat by dual-fluorescence in situ hybridization. About 81.89 % of glutamatergic LRN neurons coexpressed VGLUT1 and VGLUT2 mRNA, and the others expressed either VGLUT1 or VGLUT2 mRNA. We then injected the retrograde tracer Fluogold (FG) into the vermal cortex of cerebellum, and observed that 95.01 % and 86.80 % of FG-labeled LRN neurons expressed VGLUT1 or VGLUT2 mRNA respectively. We further injected the anterograde tracer biotinylated dextran amine (BDA) into the LRN, and found about 82.6 % of BDA labeled axon terminals in the granular layer of cerebellar cortex showed both VGLUT1- and VGLUT2-immunoreactivities. Afterwards, we observed under electron microscopy that anterogradely labeled axon terminals showing immunoreactivity for VGLUT1 or VGLUT2 made asymmetric synapses with dendritic profiles of cerebellar neurons. Finally, we selectively down-regulated the expression of VGLUT1 mRNA or VGLUT2 mRNA by using viral vector mediated siRNA transfection and detected that the fine movements of the forelimb of rats were disturbed. These results indicated that LRN neurons coexpressing VGLUT1 and VGLUT2 project to the cerebellar cortex and these neurons might be critical in mediating the forelimb movements.


Assuntos
Cerebelo/metabolismo , Neurônios/metabolismo , Formação Reticular/metabolismo , Proteína Vesicular 1 de Transporte de Glutamato/biossíntese , Proteína Vesicular 2 de Transporte de Glutamato/biossíntese , Animais , Cerebelo/citologia , Expressão Gênica , Masculino , Ratos , Ratos Sprague-Dawley , Formação Reticular/citologia , Proteína Vesicular 1 de Transporte de Glutamato/genética , Proteína Vesicular 2 de Transporte de Glutamato/genética
16.
Neurosci Lett ; 733: 135088, 2020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32464262

RESUMO

Orexin/hypocretin has been implicated in central motor control. The gigantocellular reticular nucleus (Gi), a key element of the brainstem motor inhibitory system, also receives orexinergic innervations. However, the modulations of orexin on the neuronal activities and the underlying cellular mechanisms in Gi neurons remain unknown. Here, through whole-cell patch-clamp recordings, we first observed that orexin increased the firing frequency in Gi neurons. Interestingly, a postsynaptic depolarization elicited by orexin was observed in the presence of tetrodotoxin, without altering the input resistance of Gi neurons at around -60 mV. Moreover, through comparing the current-frequency curves constructed by identical current injections from equal membrane potentials, we found that orexin also increased the repetitive firing ability of Gi neurons. This action appeared to be caused by the shortening of inter-spike intervals, without altering the waveform of individual action potentials. We finally revealed that activation of the non-selective cationic conductance contributed to the orexin-elicited excitation in Gi neurons. Together, these results suggest that orexin may facilitate Gi-mediated motor functions through enhancing the neuronal activities of Gi neurons.


Assuntos
Neurônios/metabolismo , Orexinas/metabolismo , Formação Reticular/metabolismo , Potenciais de Ação/fisiologia , Animais , Técnicas de Cultura de Órgãos , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley
17.
J Stroke Cerebrovasc Dis ; 29(7): 104857, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32409256

RESUMO

BACKGROUND AND PURPOSE: Gait disturbance due to injuries of the descending motor pathway, including corticospinal tract (CST), corticoreticular pathway (CRP), and medial and lateral vestibulospinal tracts (VSTs), are commonly encountered disabling sequelae of pontine hemorrhage. We investigated relations between changes in the CST, CRP, and medial and lateral VST and corresponding changes in gait function in patients with pontine hemorrhage. METHOD: Nine consecutive stroke patients with pontine hemorrhage, and 6 age-matched normal subjects were recruited. Four patients were allocated to group A (can't walk independently) and 5 to group B (can walk independently). Diffusion tensor imaging (DTI) data were acquired twice at acute to subacute stage and chronic stage after stroke onset. Diffusion tensor tractography (DTT) was used to reconstruct CST, CRP, medial and lateral VST. RESULT: The CRP shows a significantly different between groups A and B in both initial and follow up DTT (p > 0.05). In contrast, CST, medial VST and lateral VST did not show a significant difference (p > 0.05). Regarding DTI parameters of CRPs in group A, percentages of patients with fractional anisotropy (FA) and mean diffusivity (MD) values more than two standard deviation from normal were higher by follow up DTI than by initial DTI, however, the CRPs in group B only showed increased abnormal range of MD. CONCLUSIONS: The CST does not play an essential role in recovery of independent walking and vestibulospinal tracts may not crucially affect recovery of independent walking in patients with pontine hemorrhage. In contrast, and intact CRP or changes of the CRP integrity appear to be related to the recovery of gait function.


Assuntos
Deambulação com Auxílio , Vias Eferentes/fisiopatologia , Marcha , Hemorragias Intracranianas/fisiopatologia , Limitação da Mobilidade , Ponte/irrigação sanguínea , Adulto , Idoso , Estudos de Casos e Controles , Imagem de Tensor de Difusão , Vias Eferentes/diagnóstico por imagem , Feminino , Humanos , Hemorragias Intracranianas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/fisiopatologia , Recuperação de Função Fisiológica , Formação Reticular/diagnóstico por imagem , Formação Reticular/fisiopatologia , Núcleo Vestibular Lateral/diagnóstico por imagem , Núcleo Vestibular Lateral/fisiopatologia
19.
Int J Neurosci ; 130(2): 124-129, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31524551

RESUMO

Objectives: No studies have investigated differences in injury of the corticospinal tract (CST) and corticoreticulospinal tract (CRT) following diffuse axonal injury (DAI) to date. Therefore, we investigated differences in injury of the CST and CRT in patients with DAI using diffusion tensor tractography (DTT).Methods: Twenty consecutive patients with DAI and 20 control subjects were recruited. CST and CRT were reconstructed. Each part of the CST and CRT was analyzed in terms of DTT parameters and configuration.Results: Upon group analysis, decreased FA and TV values were observed in both the CST and CRT in the patient group compared with the control group (%) (p < .05). In the individual analysis in terms of the TV, significantly higher injury incidence was observed for the CRT (47.5%) than the CST (25.0%) (p < .05). Evaluation of the DTT configuration revealed significantly higher injury incidence for the CRT (50.0%) than the CST (17.5%) (p < .05). Specifically, the incidence of discontinuation was significantly higher for the CRT (40.0%) than the CST (10.0%) (p < .05).Conclusions: Injury of the CST and CRT was detected in patients with DAI using DTT. In terms of the incidence and severity of neural injury, the CRT appeared to be more vulnerable to DAI than the CST.


Assuntos
Lesão Axonal Difusa/patologia , Imagem de Tensor de Difusão , Tratos Piramidais/patologia , Formação Reticular/patologia , Adulto , Idoso , Lesão Axonal Difusa/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/lesões , Formação Reticular/diagnóstico por imagem , Formação Reticular/lesões , Adulto Jovem
20.
J Neurosci ; 39(49): 9757-9766, 2019 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-31666354

RESUMO

Breathing results from sequential recruitment of muscles in the expiratory, inspiratory, and postinspiratory (post-I) phases of the respiratory cycle. Here we investigate whether neurons in the medullary intermediate reticular nucleus (IRt) are components of a central pattern generator (CPG) that generates post-I activity in laryngeal adductors and vasomotor sympathetic nerves and interacts with other members of the central respiratory network to terminate inspiration. We first identified the region of the (male) rat IRt that contains the highest density of lightly cholinergic neurons, many of which are glutamatergic, which aligns well with the putative postinspiratory complex in the mouse (Anderson et al., 2016). Acute bilateral inhibition of this region reduced the amplitudes of post-I vagal and sympathetic nerve activities. However, although associated with reduced expiratory duration and increased respiratory frequency, IRt inhibition did not affect inspiratory duration or abolish the recruitment of post-I activity during acute hypoxemia as predicted. Rather than representing an independent CPG for post-I activity, we hypothesized that IRt neurons may instead function as a relay that distributes post-I activity generated elsewhere, and wondered whether they could be a site of integration for para-respiratory CPGs that drive the same outputs. Consistent with this idea, IRt inhibition blocked rhythmic motor and autonomic components of fictive swallow but not swallow-related apnea. Our data support a role for IRt neurons in the transmission of post-I and swallowing activity to motor and sympathetic outputs, but suggest that other mechanisms also contribute to the generation of post-I activity.SIGNIFICANCE STATEMENT Interactions between multiple coupled oscillators underlie a three-part respiratory cycle composed from inspiratory, postinspiratory (post-I), and late-expiratory phases. Central post-I activity terminates inspiration and activates laryngeal motoneurons. We investigate whether neurons in the intermediate reticular nucleus (IRt) form the central pattern generator (CPG) responsible for post-I activity. We confirm that IRt activity contributes to post-I motor and autonomic outputs, and find that IRt neurons are necessary for activation of the same outputs during swallow, but that they are not required for termination of inspiration or recruitment of post-I activity during hypoxemia. We conclude that this population may not represent a distinct CPG, but instead may function as a premotor relay that integrates activity generated by diverse respiratory and nonrespiratory CPGs.


Assuntos
Geradores de Padrão Central/fisiologia , Deglutição/fisiologia , Neurônios/fisiologia , Mecânica Respiratória/fisiologia , Formação Reticular/fisiologia , Sistema Nervoso Simpático/fisiologia , Animais , Apneia/fisiopatologia , Colina O-Acetiltransferase/fisiologia , Feminino , Hipercapnia/fisiopatologia , Hipóxia/fisiopatologia , Laringe/fisiologia , Masculino , Camundongos , Rede Nervosa/fisiologia , Ratos , Nervo Vago/fisiologia
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