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1.
Nature ; 590(7846): 445-450, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33408409

RESUMO

The brainstem is a key centre in the control of body movements. Although the precise nature of brainstem cell types and circuits that are central to full-body locomotion are becoming known1-5, efforts to understand the neuronal underpinnings of skilled forelimb movements have focused predominantly on supra-brainstem centres and the spinal cord6-12. Here we define the logic of a functional map for skilled forelimb movements within the lateral rostral medulla (latRM) of the brainstem. Using in vivo electrophysiology in freely moving mice, we reveal a neuronal code with tuning of latRM populations to distinct forelimb actions. These include reaching and food handling, both of which are impaired by perturbation of excitatory latRM neurons. Through the combinatorial use of genetics and viral tracing, we demonstrate that excitatory latRM neurons segregate into distinct populations by axonal target, and act through the differential recruitment of intra-brainstem and spinal circuits. Investigating the behavioural potential of projection-stratified latRM populations, we find that the optogenetic stimulation of these populations can elicit diverse forelimb movements, with each behaviour stably expressed by individual mice. In summary, projection-stratified brainstem populations encode action phases and together serve as putative building blocks for regulating key features of complex forelimb movements, identifying substrates of the brainstem for skilled forelimb behaviours.


Assuntos
Tronco Encefálico/citologia , Tronco Encefálico/fisiologia , Membro Anterior/inervação , Membro Anterior/fisiologia , Destreza Motora/fisiologia , Vias Neurais , Animais , Feminino , Masculino , Bulbo/citologia , Bulbo/fisiologia , Camundongos , Movimento
2.
J Vis Exp ; (162)2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32894269

RESUMO

In vitro slice electrophysiology techniques measure single-cell activity with precise electrical and temporal resolution. Brain slices must be relatively thin to properly visualize and access neurons for patch-clamping or imaging, and in vitro examination of brain circuitry is limited to only what is physically present in the acute slice. To maintain the benefits of in vitro slice experimentation while preserving a larger portion of presynaptic nuclei, we developed a novel slice preparation. This "wedge slice" was designed for patch-clamp electrophysiology recordings to characterize the diverse monaural, sound-driven inputs to medial olivocochlear (MOC) neurons in the brainstem. These neurons receive their primary afferent excitatory and inhibitory inputs from neurons activated by stimuli in the contralateral ear and corresponding cochlear nucleus (CN). An asymmetrical brain slice was designed which is thickest in the rostro-caudal domain at the lateral edge of one hemisphere and then thins towards the lateral edge of the opposite hemisphere. This slice contains, on the thick side, the auditory nerve root conveying information about auditory stimuli to the brain, the intrinsic CN circuitry, and both the disynaptic excitatory and trisynaptic inhibitory afferent pathways that converge on contralateral MOC neurons. Recording is performed from MOC neurons on the thin side of the slice, where they are visualized using DIC optics for typical patch-clamp experiments. Direct stimulation of the auditory nerve is performed as it enters the auditory brainstem, allowing for intrinsic CN circuit activity and synaptic plasticity to occur at synapses upstream of MOC neurons. With this technique, one can mimic in vivo circuit activation as closely as possible within the slice. This wedge slice preparation is applicable to other brain circuits where circuit analyses would benefit from preservation of upstream connectivity and long-range inputs, in combination with the technical advantages of in vitro slice physiology.


Assuntos
Tronco Encefálico/citologia , Tronco Encefálico/fisiologia , Conectoma/métodos , Neurônios/fisiologia , Animais , Vias Auditivas/fisiologia , Nervo Coclear/fisiologia , Núcleo Coclear/citologia , Núcleo Coclear/fisiologia , Núcleo Olivar/citologia , Núcleo Olivar/fisiologia , Técnicas de Patch-Clamp , Sinapses/fisiologia
3.
Nat Commun ; 11(1): 3342, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620835

RESUMO

Subdivisions of mouse whisker somatosensory thalamus project to cortex in a region-specific and layer-specific manner. However, a clear anatomical dissection of these pathways and their functional properties during whisker sensation is lacking. Here, we use anterograde trans-synaptic viral vectors to identify three specific thalamic subpopulations based on their connectivity with brainstem. The principal trigeminal nucleus innervates ventral posterior medial thalamus, which conveys whisker-selective tactile information to layer 4 primary somatosensory cortex that is highly sensitive to self-initiated movements. The spinal trigeminal nucleus innervates a rostral part of the posterior medial (POm) thalamus, signaling whisker-selective sensory information, as well as decision-related information during a goal-directed behavior, to layer 4 secondary somatosensory cortex. A caudal part of the POm, which apparently does not receive brainstem input, innervates layer 1 and 5A, responding with little whisker selectivity, but showing decision-related modulation. Our results suggest the existence of complementary segregated information streams to somatosensory cortices.


Assuntos
Córtex Cerebral/fisiologia , Vias Neurais/fisiologia , Córtex Somatossensorial/fisiologia , Tálamo/fisiologia , Tato/fisiologia , Vibrissas/fisiologia , Animais , Tronco Encefálico/citologia , Tronco Encefálico/fisiologia , Córtex Cerebral/citologia , Feminino , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/fisiologia , Córtex Somatossensorial/citologia , Transmissão Sináptica , Tálamo/citologia , Vibrissas/inervação
4.
Nat Commun ; 11(1): 3661, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32694504

RESUMO

The relationship between orexin/hypocretin and rapid eye movement (REM) sleep remains elusive. Here, we find that a proportion of orexin neurons project to the sublaterodorsal tegmental nucleus (SLD) and exhibit REM sleep-related activation. In SLD, orexin directly excites orexin receptor-positive neurons (occupying ~3/4 of total-population) and increases gap junction conductance among neurons. Their interaction spreads the orexin-elicited partial-excitation to activate SLD network globally. Besides, the activated SLD network exhibits increased probability of synchronized firings. This synchronized excitation promotes the correspondence between SLD and its downstream target to enhance SLD output. Using optogenetics and fiber-photometry, we consequently find that orexin-enhanced SLD output prolongs REM sleep episodes through consolidating brain state activation/muscle tone inhibition. After chemogenetic silencing of SLD orexin signaling, a ~17% reduction of REM sleep amounts and disruptions of REM sleep muscle atonia are observed. These findings reveal a stabilization role of orexin in REM sleep.


Assuntos
Tronco Encefálico/fisiologia , Orexinas/metabolismo , Privação do Sono/fisiopatologia , Sono REM/fisiologia , Potenciais de Ação/fisiologia , Animais , Comportamento Animal , Tronco Encefálico/citologia , Modelos Animais de Doenças , Eletrodos Implantados , Eletroencefalografia , Eletromiografia , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Tono Muscular/fisiologia , Neurônios/metabolismo , Optogenética , Receptores de Orexina/metabolismo , Orexinas/genética , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Vigília/fisiologia
5.
Am J Physiol Regul Integr Comp Physiol ; 319(1): R60-R68, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32493037

RESUMO

In the central nervous system (CNS), nuclei of the brain stem play a critical role in the integration of peripheral sensory information and the regulation of autonomic output in mammalian physiology. The nucleus tractus solitarius of the brain stem acts as a relay center that receives peripheral sensory input from vagal afferents of the nodose ganglia, integrates information from within the brain stem and higher central centers, and then transmits autonomic efferent output through downstream premotor nuclei, such as the nucleus ambiguus, the dorsal motor nucleus of the vagus, and the rostral ventral lateral medulla. Although there is mounting evidence that sex and sex hormones modulate autonomic physiology at the level of the CNS, the mechanisms and neurocircuitry involved in producing these functional consequences are poorly understood. Of particular interest in this review is the role of estrogen, progesterone, and 5α-reductase-dependent neurosteroid metabolites of progesterone (e.g., allopregnanolone) in the modulation of neurotransmission within brain-stem autonomic neurocircuits. This review will discuss our understanding of the actions and mechanisms of estrogen, progesterone, and neurosteroids at the cellular level of brain-stem nuclei. Understanding the complex interaction between sex hormones and neural signaling plasticity of the autonomic nervous system is essential to elucidating the role of sex in overall physiology and disease.


Assuntos
Sistema Nervoso Autônomo/fisiologia , Tronco Encefálico/fisiologia , Hormônios Esteroides Gonadais/fisiologia , Rede Nervosa/fisiologia , Plasticidade Neuronal/fisiologia , Animais , Feminino , Humanos , Masculino
6.
Nat Neurosci ; 23(8): 959-967, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32572237

RESUMO

The hypothalamus is composed of many neuropeptidergic cell populations and directs multiple survival behaviors, including defensive responses to threats. However, the relationship between the peptidergic identity of neurons and their roles in behavior remains unclear. Here, we address this issue by studying the function of multiple neuronal populations in the zebrafish hypothalamus during defensive responses to a variety of homeostatic threats. Cellular registration of large-scale neural activity imaging to multiplexed in situ gene expression revealed that neuronal populations encoding behavioral features encompass multiple overlapping sets of neuropeptidergic cell classes. Manipulations of different cell populations showed that multiple sets of peptidergic neurons play similar behavioral roles in this fast-timescale behavior through glutamate co-release and convergent output to spinal-projecting premotor neurons in the brainstem. Our findings demonstrate that homeostatic threats recruit neurons across multiple hypothalamic cell populations, which cooperatively drive robust defensive behaviors.


Assuntos
Comportamento Animal/fisiologia , Tronco Encefálico/fisiologia , Hipotálamo/fisiologia , Neurônios/fisiologia , Peixe-Zebra/fisiologia , Animais , Cálcio/metabolismo , Vias Neurais/fisiologia
7.
Nat Neurosci ; 23(6): 730-740, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32393896

RESUMO

Descending command neurons instruct spinal networks to execute basic locomotor functions, such as gait and speed. The command functions for gait and speed are symmetric, implying that a separate unknown system directs asymmetric movements, including the ability to move left or right. In the present study, we report that Chx10-lineage reticulospinal neurons act to control the direction of locomotor movements in mammals. Chx10 neurons exhibit mainly ipsilateral projection, and their selective unilateral activation causes ipsilateral turning movements in freely moving mice. Unilateral inhibition of Chx10 neurons causes contralateral turning movements. Paired left-right motor recordings identified distinct mechanisms for directional movements mediated via limb and axial spinal circuits. Finally, we identify sensorimotor brain regions that project on to Chx10 reticulospinal neurons, and demonstrate that their unilateral activation can impart left-right directional commands. Together these data identify the descending motor system that commands left-right locomotor asymmetries in mammals.


Assuntos
Tronco Encefálico/fisiologia , Vias Eferentes/fisiologia , Locomoção/fisiologia , Neurônios/fisiologia , Animais , Clozapina/análogos & derivados , Clozapina/farmacologia , Proteínas de Homeodomínio/imunologia , Camundongos , Técnicas de Rastreamento Neuroanatômico , Neurônios/efeitos dos fármacos , Toxina Tetânica/farmacologia , Fatores de Transcrição/imunologia
8.
J Neurosci ; 40(3): 509-525, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31719165

RESUMO

Medial olivocochlear (MOC) efferent neurons in the brainstem comprise the final stage of descending control of the mammalian peripheral auditory system through axon projections to the cochlea. MOC activity adjusts cochlear gain and frequency tuning, and protects the ear from acoustic trauma. The neuronal pathways that activate and modulate the MOC somata in the brainstem to drive these cochlear effects are poorly understood. Evidence suggests that MOC neurons are primarily excited by sound stimuli in a three-neuron activation loop from the auditory nerve via an intermediate neuron in the cochlear nucleus. Anatomical studies suggest that MOC neurons receive diverse synaptic inputs, but the functional effect of additional synaptic influences on MOC neuron responses is unknown. Here we use patch-clamp electrophysiological recordings from identified MOC neurons in brainstem slices from mice of either sex to demonstrate that in addition to excitatory glutamatergic synapses, MOC neurons receive inhibitory GABAergic and glycinergic synaptic inputs. These synapses are activated by electrical stimulation of axons near the medial nucleus of the trapezoid body (MNTB). Focal glutamate uncaging confirms MNTB neurons as a source of inhibitory synapses onto MOC neurons. MNTB neurons inhibit MOC action potentials, but this effect depresses with repeat activation. This work identifies a new pathway of connectivity between brainstem auditory neurons and indicates that MOC neurons are both excited and inhibited by sound stimuli received at the same ear. The pathway depression suggests that the effect of MNTB inhibition of MOC neurons diminishes over the course of a sustained sound.SIGNIFICANCE STATEMENT Medial olivocochlear (MOC) neurons are the final stage of descending control of the mammalian auditory system and exert influence on cochlear mechanics to modulate perception of acoustic stimuli. The brainstem pathways that drive MOC function are poorly understood. Here we show for the first time that MOC neurons are inhibited by neurons of the MNTB, which may suppress the effects of MOC activity on the cochlea.


Assuntos
Núcleo Coclear/fisiologia , Neurônios Eferentes/fisiologia , Núcleo Olivar/fisiologia , Corpo Trapezoide/fisiologia , Estimulação Acústica , Animais , Axônios/fisiologia , Tronco Encefálico/citologia , Tronco Encefálico/fisiologia , Nervo Coclear/fisiologia , Núcleo Coclear/citologia , Estimulação Elétrica , Potenciais Pós-Sinápticos Excitadores/genética , Potenciais Pós-Sinápticos Excitadores/fisiologia , Feminino , Glutamatos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Núcleo Olivar/citologia , Técnicas de Patch-Clamp , Sinapses/fisiologia , Corpo Trapezoide/citologia
9.
Neurol Sci ; 41(3): 611-617, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31732889

RESUMO

BACKGROUND AND AIM: Sound lateralization/localization is one of the most important auditory processing abilities, which plays approved role in auditory streaming and speech perception in challenging situations like noisy places. In addition to the main role of lower brainstem centers like superior olivary complex in sound lateralization, efferent auditory system effects on improving auditory skills in everyday auditory challenging positions were revealed. This study evaluated noise effects on lateralization scores in correlation with an objective electrophysiologic test (Speech-ABR in noise), which objectively shows cumulative effects of the afferent and efferent auditory systems at the inferior colliculus and upper brainstem pathway. METHOD: Fourteen normal-hearing subjects in the age range of 18 to 25 participated in this study. Lateralization scores in the quiet and noisy modes were evaluated. Speech-ABR in both ears for quiet mode and three different contralateral noise levels (SNR = + 5, 0, - 5) were recorded, too. Correlation of lateralization scores and Speech-ABR changes in noise was studied. RESULTS: Significant decrease of lateralization scores with latency increase and amplitude decrease of Speech-ABR transient peaks (V, A, O) was seen with noise presentation. A high positive correlation between lateralization decrease with latency increase of onset peaks (V, A) and amplitude decrease of transient peaks (V, A, O) was found in low signal-to-noise ratios. CONCLUSION: The study revealed that in high challenging auditory situations like auditory lateralization in noise, upper brainstem centers and pathways play a facilitative role for main auditory lateralization centers in lower levels.


Assuntos
Vias Auditivas/fisiologia , Tronco Encefálico/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Localização de Som/fisiologia , Percepção da Fala/fisiologia , Adolescente , Adulto , Mapeamento Encefálico , Eletroencefalografia , Feminino , Humanos , Colículos Inferiores/fisiologia , Masculino , Ruído , Adulto Jovem
10.
J Neurosci ; 40(1): 131-142, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31767677

RESUMO

Cytoskeletal filaments such as microtubules (MTs) and filamentous actin (F-actin) dynamically support cell structure and functions. In central presynaptic terminals, F-actin is expressed along the release edge and reportedly plays diverse functional roles, but whether axonal MTs extend deep into terminals and play any physiological role remains controversial. At the calyx of Held in rats of either sex, confocal and high-resolution microscopy revealed that MTs enter deep into presynaptic terminal swellings and partially colocalize with a subset of synaptic vesicles (SVs). Electrophysiological analysis demonstrated that depolymerization of MTs specifically prolonged the slow-recovery time component of EPSCs from short-term depression induced by a train of high-frequency stimulation, whereas depolymerization of F-actin specifically prolonged the fast-recovery component. In simultaneous presynaptic and postsynaptic action potential recordings, depolymerization of MTs or F-actin significantly impaired the fidelity of high-frequency neurotransmission. We conclude that MTs and F-actin differentially contribute to slow and fast SV replenishment, thereby maintaining high-frequency neurotransmission.SIGNIFICANCE STATEMENT The presence and functional role of MTs in the presynaptic terminal are controversial. Here, we demonstrate that MTs are present near SVs in calyceal presynaptic terminals and that MT depolymerization specifically prolongs the slow-recovery component of EPSCs from short-term depression. In contrast, F-actin depolymerization specifically prolongs fast-recovery component. Depolymerization of MT or F-actin has no direct effect on SV exocytosis/endocytosis or basal transmission, but significantly impairs the fidelity of high-frequency transmission, suggesting that presynaptic cytoskeletal filaments play essential roles in SV replenishment for the maintenance of high-frequency neurotransmission.


Assuntos
Citoesqueleto de Actina/fisiologia , Exocitose/fisiologia , Microtúbulos/fisiologia , Transmissão Sináptica/fisiologia , Vesículas Sinápticas/fisiologia , Actinas/fisiologia , Animais , Vias Auditivas/fisiologia , Tronco Encefálico/citologia , Tronco Encefálico/fisiologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Feminino , Masculino , Terminações Pré-Sinápticas/fisiologia , Ratos , Ratos Wistar , Transmissão Sináptica/efeitos dos fármacos , Tiazolidinas/farmacologia , Corpo Trapezoide/fisiologia , Vimblastina/farmacologia
11.
Neuroimage ; 204: 116239, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31586673

RESUMO

In animal models, exposure to high noise levels can cause permanent damage to hair-cell synapses (cochlear synaptopathy) for high-threshold auditory nerve fibers without affecting sensitivity to quiet sounds. This has been confirmed in several mammalian species, but the hypothesis that lifetime noise exposure affects auditory function in humans with normal audiometric thresholds remains unconfirmed and current evidence from human electrophysiology is contradictory. Here we report the auditory brainstem response (ABR), and both transient (stimulus onset and offset) and sustained functional magnetic resonance imaging (fMRI) responses throughout the human central auditory pathway across lifetime noise exposure. Healthy young individuals aged 25-40 years were recruited into high (n = 32) and low (n = 30) lifetime noise exposure groups, stratified for age, and balanced for audiometric threshold up to 16 kHz fMRI demonstrated robust broadband noise-related activity throughout the auditory pathway (cochlear nucleus, superior olivary complex, nucleus of the lateral lemniscus, inferior colliculus, medial geniculate body and auditory cortex). fMRI responses in the auditory pathway to broadband noise onset were significantly enhanced in the high noise exposure group relative to the low exposure group, differences in sustained fMRI responses did not reach significance, and no significant group differences were found in the click-evoked ABR. Exploratory analyses found no significant relationships between the neural responses and self-reported tinnitus or reduced sound-level tolerance (symptoms associated with synaptopathy). In summary, although a small effect, these fMRI results suggest that lifetime noise exposure may be associated with central hyperactivity in young adults with normal hearing thresholds.


Assuntos
Córtex Auditivo/fisiologia , Vias Auditivas/fisiologia , Percepção Auditiva/fisiologia , Limiar Auditivo/fisiologia , Tronco Encefálico/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Neuroimagem Funcional , Ruído/efeitos adversos , Adulto , Córtex Auditivo/diagnóstico por imagem , Tronco Encefálico/diagnóstico por imagem , Núcleo Coclear/diagnóstico por imagem , Núcleo Coclear/fisiologia , Eletroencefalografia , Feminino , Corpos Geniculados/diagnóstico por imagem , Corpos Geniculados/fisiologia , Humanos , Colículos Inferiores/diagnóstico por imagem , Colículos Inferiores/fisiologia , Imagem por Ressonância Magnética , Masculino , Complexo Olivar Superior/diagnóstico por imagem , Complexo Olivar Superior/fisiologia
12.
J Perinatol ; 40(2): 203-211, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31263204

RESUMO

OBJECTIVE: To evaluate the feasibility of auditory monitoring of neurophysiological status using frequency-following response (FFR) in neonates with progressive moderate hyperbilirubinemia, measured by transcutaneous (TcB) levels. STUDY DESIGN: ABR and FFR measures were compared and correlated with TcB levels across three groups. Group I was a healthy cohort (n = 13). Group II (n = 28) consisted of neonates with progressive, moderate hyperbilirubinemia and Group III consisted of the same neonates, post physician-ordered phototherapy. RESULT: FFR amplitudes in Group I controls (TcB = 83.1 ± 32.5µmol/L; 4.9 ± 1.9 mg/dL) were greater than Group II (TcB = 209.3 ± 48.0µmol/L; 12.1 ± 2.8 mg/dL). After TcB was lowered by phototherapy, FFR amplitudes in Group III were similar to controls. Lower TcB levels correlated with larger FFR amplitudes (r = -0.291, p = 0.015), but not with ABR wave amplitude or latencies. CONCLUSION: The FFR is a promising measure of the dynamic neurophysiological status in neonates, and may be useful in tracking neurotoxicity in infants with hyperbilirubinemia.


Assuntos
Estimulação Acústica , Tronco Encefálico/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico , Hiperbilirrubinemia Neonatal/fisiopatologia , Triagem Neonatal/métodos , Bilirrubina/sangue , Estudos de Coortes , Eletroencefalografia , Humanos , Hiperbilirrubinemia Neonatal/sangue , Hiperbilirrubinemia Neonatal/terapia , Recém-Nascido , Fototerapia , Fala
13.
Am J Physiol Regul Integr Comp Physiol ; 318(2): R191-R205, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31664868

RESUMO

This review is based on the Carl Ludwig Distinguished Lecture, presented at the 2019 Experimental Biology Meeting in Orlando, FL, and provides a snapshot of >40 years of work done in collaboration with the late Gerard L. Gebber and colleagues to highlight the importance of considering the rhythmic properties of sympathetic nerve activity (SNA) and brain stem neurons when studying the neural control of autonomic regulation. After first providing some basic information about rhythms, I describe the patterns and potential functions of rhythmic activity recorded from sympathetic nerves under various physiological conditions. I review the evidence that these rhythms reflect the properties of central sympathetic neural networks that include neurons in the caudal medullary raphe, caudal ventrolateral medulla, caudal ventrolateral pons, medullary lateral tegmental field, rostral dorsolateral pons, and rostral ventrolateral medulla. The role of these brain stem areas in mediating steady-state and reflex-induced changes in SNA and blood pressure is discussed. Despite the common appearance of rhythms in SNA, these oscillatory characteristics are often ignored; instead, it is common to simply quantify changes in the amount of SNA to make conclusions about the function of the sympathetic nervous system in mediating responses to a variety of stimuli. This review summarizes work that highlights the need to include an assessment of the changes in the frequency components of SNA in evaluating the cardiovascular responses to various manipulations as well as in determining the role of different brain regions in the neural control of the cardiovascular system.


Assuntos
Tronco Encefálico/fisiologia , Sistema Cardiovascular/inervação , Hemodinâmica , Periodicidade , Reflexo , Sistema Nervoso Simpático/fisiologia , Animais , Humanos , Fatores de Tempo
14.
Nat Commun ; 10(1): 5309, 2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796727

RESUMO

Bioelectronic medicine is driving the need for neuromorphic microcircuits that integrate raw nervous stimuli and respond identically to biological neurons. However, designing such circuits remains a challenge. Here we estimate the parameters of highly nonlinear conductance models and derive the ab initio equations of intracellular currents and membrane voltages embodied in analog solid-state electronics. By configuring individual ion channels of solid-state neurons with parameters estimated from large-scale assimilation of electrophysiological recordings, we successfully transfer the complete dynamics of hippocampal and respiratory neurons in silico. The solid-state neurons are found to respond nearly identically to biological neurons under stimulation by a wide range of current injection protocols. The optimization of nonlinear models demonstrates a powerful method for programming analog electronic circuits. This approach offers a route for repairing diseased biocircuits and emulating their function with biomedical implants that can adapt to biofeedback.


Assuntos
Neurônios/fisiologia , Animais , Tronco Encefálico/fisiologia , Hipocampo/fisiologia , Ativação do Canal Iônico , Canais Iônicos/metabolismo , Masculino , Modelos Neurológicos , Células Piramidais/fisiologia , Ratos Wistar , Respiração
15.
Sci Rep ; 9(1): 18360, 2019 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-31798010

RESUMO

Body weight (BW) is regulated in age-dependent manner; it continues to increase during growth period, and reaches a plateau once reaching adulthood. However, its underlying mechanism remains unknown. Regarding such mechanisms in the brain, we here report that neural circuits from the hypothalamus (paraventricular nucleus: PVN) to the brainstem (dorsal vagal complex: DVC) suppress late-onset BW gain without affecting food intake. The genetic suppression of the PVN-DVC circuit induced BW increase only in aged rats, indicating that this circuit contributes to suppress the BW at a fixed level after reaching adulthood. PVN neurons in the hypothalamus were inactive in younger rats but active in aged rats. The density of neuropeptide Y (NPY) terminal/fiber is reduced in the aged rat PVN area. The differences in neuronal activity, including oxytocin neurons in the PVN, were affected by the application of NPY or its receptor inhibitor, indicating that NPY is a possible regulator of this pathway. Our data provide new insights into understanding age-dependent BW regulation.


Assuntos
Tronco Encefálico/fisiologia , Ingestão de Alimentos/fisiologia , Hipotálamo/fisiologia , Ganho de Peso/fisiologia , Animais , Peso Corporal/fisiologia , Humanos , Neurônios/fisiologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Ratos
16.
Compr Physiol ; 9(4): 1503-1575, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31688966

RESUMO

Spatial hearing, and more specifically the ability to localize sounds in space, is one of the most studied and best understood aspects of hearing. Because there is no coding of acoustic space at the receptor organ, physiological sensitivity to spatial aspects of sounds first emerges in the central nervous system. Much progress has been made in the identification and characterization of the circuits in the auditory brainstem that create sensitivity to binaural and monaural cues toward acoustic space. We review the progress over the past third of a century, with a focus on the mammalian brainstem and on the anatomy and cellular physiology underlying the physiological tuning of monaural and binaural circuits to acoustic cues toward spatial hearing. In addition to examining the detailed mechanisms involved in the processing of the three main spatial cues, we also review the integration of these cues and their use toward behavior. © 2019 American Physiological Society. Compr Physiol 9:1503-1575, 2019.


Assuntos
Vias Auditivas/fisiologia , Tronco Encefálico/fisiologia , Audição/fisiologia , Localização de Som/fisiologia , Animais , Cóclea/citologia , Cóclea/fisiologia , Humanos , Neurônios/fisiologia
17.
Science ; 366(6468): 1008-1012, 2019 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-31754002

RESUMO

What individual differences in neural activity predict the future escalation of alcohol drinking from casual to compulsive? The neurobiological mechanisms that gate the transition from moderate to compulsive drinking remain poorly understood. We longitudinally tracked the development of compulsive drinking across a binge-drinking experience in male mice. Binge drinking unmasked individual differences, revealing latent traits in alcohol consumption and compulsive drinking despite equal prior exposure to alcohol. Distinct neural activity signatures of cortical neurons projecting to the brainstem before binge drinking predicted the ultimate emergence of compulsivity. Mimicry of activity patterns that predicted drinking phenotypes was sufficient to bidirectionally modulate drinking. Our results provide a mechanistic explanation for individual variance in vulnerability to compulsive alcohol drinking.


Assuntos
Consumo de Bebidas Alcoólicas , Bebedeira , Tronco Encefálico/fisiologia , Comportamento Compulsivo , Neurônios/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Córtex Pré-Frontal/fisiologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vias Neurais/fisiologia , Quinina/administração & dosagem
18.
J Neurophysiol ; 122(6): 2576-2590, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31577531

RESUMO

Single neurons function along a spectrum of neuronal operating modes whose properties determine how the output firing activity is generated from synaptic input. The auditory brain stem contains a diversity of neurons, from pure coincidence detectors to pure integrators and those with intermediate properties. We investigated how intrinsic spike initiation mechanisms regulate neuronal operating mode in the avian cochlear nucleus. Although the neurons in one division of the avian cochlear nucleus, nucleus magnocellularis, have been studied in depth, the spike threshold dynamics of the tonically firing neurons of a second division of cochlear nucleus, nucleus angularis (NA), remained unexplained. The input-output functions of tonically firing NA neurons were interrogated with directly injected in vivo-like current stimuli during whole cell patch-clamp recordings in vitro. Increasing the amplitude of the noise fluctuations in the current stimulus enhanced the firing rates in one subset of tonically firing neurons ("differentiators") but not another ("integrators"). We found that spike thresholds showed significantly greater adaptation and variability in the differentiator neurons. A leaky integrate-and-fire neuronal model with an adaptive spike initiation process derived from sodium channel dynamics was fit to the firing responses and could recapitulate >80% of the precise temporal firing across a range of fluctuation and mean current levels. Greater threshold adaptation explained the frequency-current curve changes due to a hyperpolarized shift in the effective adaptation voltage range and longer-lasting threshold adaptation in differentiators. The fine-tuning of the intrinsic properties of different NA neurons suggests they may have specialized roles in spectrotemporal processing.NEW & NOTEWORTHY Avian cochlear nucleus angularis (NA) neurons are responsible for encoding sound intensity for sound localization and spectrotemporal processing. An adaptive spike threshold mechanism fine-tunes a subset of repetitive-spiking neurons in NA to confer coincidence detector-like properties. A model based on sodium channel inactivation properties reproduced the activity via a hyperpolarized shift in adaptation conferring fluctuation sensitivity.


Assuntos
Adaptação Fisiológica/fisiologia , Tronco Encefálico/fisiologia , Núcleo Coclear/fisiologia , Fenômenos Eletrofisiológicos/fisiologia , Neurônios/fisiologia , Animais , Embrião de Galinha , Modelos Biológicos , Técnicas de Patch-Clamp , Localização de Som/fisiologia
19.
Neurosci Lett ; 713: 134529, 2019 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-31585210

RESUMO

Gastrin releasing peptide (GRP) is involved in the stimulation of gastric acid release from the stomach. It also mediates effects on feeding behavior. It is associated with anorexigenic effects in both mammalian and avian species, but the mechanism of action is unknown in any species. The aim of the present study was thus to investigate the hypothalamic and brainstem mechanisms mediating GRP-induced satiety in chicks. In Experiment 1, chicks that received intracerebroventricular (ICV) injection of GRP reduced food intake for up to 150 min following injection and reduced water intake up to 120 min following injection. In Experiment 2, chicks that were food restricted following GRP injection did not reduce water intake. Alimentary canal transit time was not affected by GRP in Experiment 3. A behavior analysis was conducted in Experiment 4, revealing that GRP-treated chicks reduced feeding pecks. In Experiment 5, GRP-treated chicks had increased c-Fos immunoreactivity in the lateral hypothalamus, paraventricular nucleus, and arcuate nucleus of the hypothalamus, and the nucleus of the solitary tract. Collectively, these results demonstrate that central GRP causes anorexigenic effects that are associated with hypothalamic changes without affecting other behaviors.


Assuntos
Tronco Encefálico/fisiologia , Peptídeo Liberador de Gastrina/fisiologia , Hipotálamo/fisiologia , Saciação/fisiologia , Animais , Comportamento Animal , Tronco Encefálico/metabolismo , Galinhas , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Peptídeo Liberador de Gastrina/administração & dosagem , Peptídeo Liberador de Gastrina/farmacologia , Trânsito Gastrointestinal/efeitos dos fármacos , Hipotálamo/metabolismo , Infusões Intraventriculares , Proteínas Proto-Oncogênicas c-fos/metabolismo
20.
J Neurophysiol ; 122(6): 2601-2613, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31664872

RESUMO

Activation of contralateral muscles by supraspinal neurons, or crossed activation, is critical for bilateral coordination. Studies in mammals have focused on the neural circuits that mediate cross activation of limb muscles, but the neural circuits involved in crossed activation of trunk muscles are still poorly understood. In this study, we characterized functional connections between reticulospinal (RS) neurons in the medial and lateral regions of the medullary reticular formation (medMRF and latMRF) and contralateral trunk motoneurons (MNs) in the thoracic cord (T7 and T10 segments). To do this, we combined electrical microstimulation of the medMRF and latMRF and calcium imaging from single cells in an ex vivo brain stem-spinal cord preparation of neonatal mice. Our findings substantiate two spatially distinct RS pathways to contralateral trunk MNs. Both pathways originate in the latMRF and are midline crossing, one at the level of the spinal cord via excitatory descending commissural interneurons (reticulo-commissural pathway) and the other at the level of the brain stem (crossed RS pathway). Activation of these RS pathways may enable different patterns of bilateral trunk coordination. Possible implications for recovery of trunk function after stroke or spinal cord injury are discussed.NEW & NOTEWORTHY We identify two spatially distinct reticulospinal pathways for crossed activation of trunk motoneurons. Both pathways cross the midline, one at the level of the brain stem and the other at the level of the spinal cord via excitatory commissural interneurons. Jointly, these pathways provide new opportunities for repair interventions aimed at recovering trunk functions after stroke or spinal cord injury.


Assuntos
Tronco Encefálico/fisiologia , Fenômenos Eletrofisiológicos/fisiologia , Interneurônios/fisiologia , Neurônios Motores/fisiologia , Medula Espinal/fisiologia , Tronco/fisiologia , Animais , Animais Recém-Nascidos , Bulbo/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Transgênicos , Formação Reticular/fisiologia
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