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1.
Neuron ; 109(19): 3135-3148.e7, 2021 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-34619088

RESUMO

The medial entorhinal cortex (MEC)-hippocampal network plays a key role in the processing, storage, and recall of spatial information. However, how the spatial code provided by MEC inputs relates to spatial representations generated by principal cell assemblies within hippocampal subfields remains enigmatic. To investigate this coding relationship, we employed two-photon calcium imaging in mice navigating through dissimilar virtual environments. Imaging large MEC bouton populations revealed spatially tuned activity patterns. MEC inputs drastically changed their preferred spatial field locations between environments, whereas hippocampal cells showed lower levels of place field reconfiguration. Decoding analysis indicated that higher place field reliability and larger context-dependent activity-rate differences allow low numbers of principal cells, particularly in the DG and CA1, to provide information about location and context more accurately and rapidly than MEC inputs. Thus, conversion of dynamic MEC inputs into stable spatial hippocampal maps may enable fast encoding and efficient recall of spatio-contextual information.


Assuntos
Córtex Entorrinal/fisiologia , Hipocampo/fisiologia , Animais , Região CA1 Hipocampal/citologia , Região CA1 Hipocampal/fisiologia , Sinalização do Cálcio , Giro Denteado/citologia , Giro Denteado/fisiologia , Córtex Entorrinal/citologia , Hipocampo/citologia , Masculino , Rememoração Mental/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Rede Nervosa/citologia , Rede Nervosa/fisiologia , Terminações Pré-Sinápticas/fisiologia , Reprodutibilidade dos Testes , Percepção Espacial/fisiologia , Realidade Virtual
2.
Nat Commun ; 12(1): 5286, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489431

RESUMO

Vomeronasal information is critical in mice for territorial behavior. Consequently, learning the territorial spatial structure should incorporate the vomeronasal signals indicating individual identity into the hippocampal cognitive map. In this work we show in mice that navigating a virtual environment induces synchronic activity, with causality in both directionalities, between the vomeronasal amygdala and the dorsal CA1 of the hippocampus in the theta frequency range. The detection of urine stimuli induces synaptic plasticity in the vomeronasal pathway and the dorsal hippocampus, even in animals with experimentally induced anosmia. In the dorsal hippocampus, this plasticity is associated with the overexpression of pAKT and pGSK3ß. An amygdalo-entorhino-hippocampal circuit likely underlies this effect of pheromonal information on hippocampal learning. This circuit likely constitutes the neural substrate of territorial behavior in mice, and it allows the integration of social and spatial information.


Assuntos
Tonsila do Cerebelo/fisiologia , Região CA1 Hipocampal/fisiologia , Glicogênio Sintase Quinase 3 beta/genética , Percepção Olfatória/fisiologia , Proteínas Proto-Oncogênicas c-akt/genética , Comportamento Espacial/fisiologia , Órgão Vomeronasal/fisiologia , Tonsila do Cerebelo/citologia , Animais , Anosmia/genética , Anosmia/metabolismo , Anosmia/fisiopatologia , Comportamento Animal , Região CA1 Hipocampal/citologia , Feminino , Regulação da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/metabolismo , Aprendizagem/fisiologia , Masculino , Camundongos , Rede Nervosa/citologia , Rede Nervosa/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/citologia , Neurônios/metabolismo , Feromônios/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Percepção Social , Percepção Espacial/fisiologia , Ritmo Teta/fisiologia , Órgão Vomeronasal/citologia
3.
Elife ; 102021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34505577

RESUMO

Cortical inactivation represents a key causal manipulation allowing the study of cortical circuits and their impact on behavior. A key assumption in inactivation studies is that the neurons in the target area become silent while the surrounding cortical tissue is only negligibly impacted. However, individual neurons are embedded in complex local circuits composed of excitatory and inhibitory cells with connections extending hundreds of microns. This raises the possibility that silencing one part of the network could induce complex, unpredictable activity changes in neurons outside the targeted inactivation zone. These off-target side effects can potentially complicate interpretations of inactivation manipulations, especially when they are related to changes in behavior. Here, we demonstrate that optogenetic inactivation of glutamatergic neurons in the superficial layers of monkey primary visual cortex (V1) induces robust suppression at the light-targeted site, but destabilizes stimulus responses in the neighboring, untargeted network. We identified four types of stimulus-evoked neuronal responses within a cortical column, ranging from full suppression to facilitation, and a mixture of both. Mixed responses were most prominent in middle and deep cortical layers. These results demonstrate that response modulation driven by lateral network connectivity is diversely implemented throughout a cortical column. Importantly, consistent behavioral changes induced by optogenetic inactivation were only achieved when cumulative network activity was homogeneously suppressed. Therefore, careful consideration of the full range of network changes outside the inactivated cortical region is required, as heterogeneous side effects can confound interpretation of inactivation experiments.


Assuntos
Comportamento Animal , Rede Nervosa/fisiologia , Plasticidade Neuronal , Optogenética/efeitos adversos , Córtex Visual/fisiologia , Percepção Visual , Animais , Channelrhodopsins/genética , Channelrhodopsins/metabolismo , Ácido Glutâmico/metabolismo , Macaca mulatta , Masculino , Rede Nervosa/citologia , Rede Nervosa/metabolismo , Estimulação Luminosa , Transmissão Sináptica , Córtex Visual/citologia , Córtex Visual/metabolismo
4.
Sci Rep ; 11(1): 17189, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433854

RESUMO

Neuronal nitric oxide synthase (nNOS) neurons play a fundamental role in inhibitory neurotransmission, within the enteric nervous system (ENS), and in the establishment of gut motility patterns. Clinically, loss or disruption of nNOS neurons has been shown in a range of enteric neuropathies. However, the effects of nNOS loss on the composition and structure of the ENS remain poorly understood. The aim of this study was to assess the structural and transcriptional consequences of loss of nNOS neurons within the murine ENS. Expression analysis demonstrated compensatory transcriptional upregulation of pan neuronal and inhibitory neuronal subtype targets within the Nos1-/- colon, compared to control C57BL/6J mice. Conventional confocal imaging; combined with novel machine learning approaches, and automated computational analysis, revealed increased interconnectivity within the Nos1-/- ENS, compared to age-matched control mice, with increases in network density, neural projections and neuronal branching. These findings provide the first direct evidence of structural and molecular remodelling of the ENS, upon loss of nNOS signalling. Further, we demonstrate the utility of machine learning approaches, and automated computational image analysis, in revealing previously undetected; yet potentially clinically relevant, changes in ENS structure which could provide improved understanding of pathological mechanisms across a host of enteric neuropathies.


Assuntos
Sistema Nervoso Entérico/metabolismo , Óxido Nítrico Sintase Tipo I/genética , Animais , Sistema Nervoso Entérico/citologia , Aprendizado de Máquina , Camundongos , Camundongos Endogâmicos C57BL , Rede Nervosa/citologia , Rede Nervosa/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Óxido Nítrico Sintase Tipo I/deficiência
5.
Nat Rev Neurosci ; 22(10): 637-649, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34453151

RESUMO

Entorhinal cortical grid cells fire in a periodic pattern that tiles space, which is suggestive of a spatial coordinate system. However, irregularities in the grid pattern as well as responses of grid cells in contexts other than spatial navigation have presented a challenge to existing models of entorhinal function. In this Perspective, we propose that hippocampal input provides a key informative drive to the grid network in both spatial and non-spatial circumstances, particularly around salient events. We build on previous models in which neural activity propagates through the entorhinal-hippocampal network in time. This temporal contiguity in network activity points to temporal order as a necessary characteristic of representations generated by the hippocampal formation. We advocate that interactions in the entorhinal-hippocampal loop build a topological representation that is rooted in the temporal order of experience. In this way, the structure of grid cell firing supports a learned topology rather than a rigid coordinate frame that is bound to measurements of the physical world.


Assuntos
Córtex Entorrinal/fisiologia , Células de Grade/fisiologia , Hipocampo/fisiologia , Aprendizagem/fisiologia , Rede Nervosa/fisiologia , Percepção Espacial/fisiologia , Animais , Córtex Entorrinal/citologia , Hipocampo/citologia , Humanos , Modelos Neurológicos , Rede Nervosa/citologia
6.
PLoS Comput Biol ; 17(8): e1009205, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34375329

RESUMO

The Drosophila mushroom body exhibits dopamine dependent synaptic plasticity that underlies the acquisition of associative memories. Recordings of dopamine neurons in this system have identified signals related to external reinforcement such as reward and punishment. However, other factors including locomotion, novelty, reward expectation, and internal state have also recently been shown to modulate dopamine neurons. This heterogeneity is at odds with typical modeling approaches in which these neurons are assumed to encode a global, scalar error signal. How is dopamine dependent plasticity coordinated in the presence of such heterogeneity? We develop a modeling approach that infers a pattern of dopamine activity sufficient to solve defined behavioral tasks, given architectural constraints informed by knowledge of mushroom body circuitry. Model dopamine neurons exhibit diverse tuning to task parameters while nonetheless producing coherent learned behaviors. Notably, reward prediction error emerges as a mode of population activity distributed across these neurons. Our results provide a mechanistic framework that accounts for the heterogeneity of dopamine activity during learning and behavior.


Assuntos
Dopamina/fisiologia , Drosophila/fisiologia , Aprendizagem/fisiologia , Memória/fisiologia , Modelos Neurológicos , Corpos Pedunculados/fisiologia , Animais , Comportamento Animal/fisiologia , Biologia Computacional , Condicionamento Clássico/fisiologia , Neurônios Dopaminérgicos/fisiologia , Drosophila/citologia , Corpos Pedunculados/citologia , Rede Nervosa/citologia , Rede Nervosa/fisiologia , Redes Neurais de Computação , Plasticidade Neuronal/fisiologia , Recompensa
7.
Elife ; 102021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34328415

RESUMO

A central theme that governs the functional design of biological networks is their ability to sustain stable function despite widespread parametric variability. Here, we investigated the impact of distinct forms of biological heterogeneities on the stability of a two-dimensional continuous attractor network (CAN) implicated in grid-patterned activity generation. We show that increasing degrees of biological heterogeneities progressively disrupted the emergence of grid-patterned activity and resulted in progressively large perturbations in low-frequency neural activity. We postulated that targeted suppression of low-frequency perturbations could ameliorate heterogeneity-induced disruptions of grid-patterned activity. To test this, we introduced intrinsic resonance, a physiological mechanism to suppress low-frequency activity, either by adding an additional high-pass filter (phenomenological) or by incorporating a slow negative feedback loop (mechanistic) into our model neurons. Strikingly, CAN models with resonating neurons were resilient to the incorporation of heterogeneities and exhibited stable grid-patterned firing. We found CAN models with mechanistic resonators to be more effective in targeted suppression of low-frequency activity, with the slow kinetics of the negative feedback loop essential in stabilizing these networks. As low-frequency perturbations (1/f noise) are pervasive across biological systems, our analyses suggest a universal role for mechanisms that suppress low-frequency activity in stabilizing heterogeneous biological networks.


Assuntos
Algoritmos , Células de Grade/fisiologia , Rede Nervosa/fisiologia , Neurônios/fisiologia , Potenciais de Ação/fisiologia , Simulação por Computador , Modelos Neurológicos , Rede Nervosa/citologia
8.
Comput Math Methods Med ; 2021: 9956319, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34221108

RESUMO

A model of time-dependent structural plasticity for the synchronization of neuron networks is presented. It is known that synchronized oscillations reproduce structured communities, and this synchronization is transient since it can be enhanced or suppressed, and the proposed model reproduces this characteristic. The evolutionary behavior of the couplings is comparable to those of a network of biological neurons. In the structural network, the physical connections of axons and dendrites between neurons are modeled, and the evolution in the connections depends on the neurons' potential. Moreover, it is shown that the coupling force's function behaves as an adaptive controller that leads the neurons in the network to synchronization. The change in the node's degree shows that the network exhibits time-dependent structural plasticity, achieved through the evolutionary or adaptive change of the coupling force between the nodes. The coupling force function is based on the computed magnitude of the membrane potential deviations with its neighbors and a threshold that determines the neuron's connections. These rule the functional network structure along the time.


Assuntos
Modelos Neurológicos , Rede Nervosa/fisiologia , Evolução Biológica , Biologia Computacional , Simulação por Computador , Fenômenos Eletrofisiológicos , Humanos , Conceitos Matemáticos , Potenciais da Membrana/fisiologia , Rede Nervosa/citologia , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia
9.
PLoS Comput Biol ; 17(6): e1009163, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34181653

RESUMO

Synchronous oscillations in neural populations are considered being controlled by inhibitory neurons. In the granular layer of the cerebellum, two major types of cells are excitatory granular cells (GCs) and inhibitory Golgi cells (GoCs). GC spatiotemporal dynamics, as the output of the granular layer, is highly regulated by GoCs. However, there are various types of inhibition implemented by GoCs. With inputs from mossy fibers, GCs and GoCs are reciprocally connected to exhibit different network motifs of synaptic connections. From the view of GCs, feedforward inhibition is expressed as the direct input from GoCs excited by mossy fibers, whereas feedback inhibition is from GoCs via GCs themselves. In addition, there are abundant gap junctions between GoCs showing another form of inhibition. It remains unclear how these diverse copies of inhibition regulate neural population oscillation changes. Leveraging a computational model of the granular layer network, we addressed this question to examine the emergence and modulation of network oscillation using different types of inhibition. We show that at the network level, feedback inhibition is crucial to generate neural oscillation. When short-term plasticity was equipped on GoC-GC synapses, oscillations were largely diminished. Robust oscillations can only appear with additional gap junctions. Moreover, there was a substantial level of cross-frequency coupling in oscillation dynamics. Such a coupling was adjusted and strengthened by GoCs through feedback inhibition. Taken together, our results suggest that the cooperation of distinct types of GoC inhibition plays an essential role in regulating synchronous oscillations of the GC population. With GCs as the sole output of the granular network, their oscillation dynamics could potentially enhance the computational capability of downstream neurons.


Assuntos
Córtex Cerebelar/citologia , Córtex Cerebelar/fisiologia , Modelos Neurológicos , Animais , Biologia Computacional , Sinapses Elétricas/fisiologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Retroalimentação Fisiológica , Humanos , Potenciais Pós-Sinápticos Inibidores/fisiologia , Fibras Nervosas/fisiologia , Rede Nervosa/citologia , Rede Nervosa/fisiologia , Vias Neurais/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Análise de Célula Única/estatística & dados numéricos , Sinapses/fisiologia
10.
Elife ; 102021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-34137370

RESUMO

In adult dentate gyrus neurogenesis, the link between maturation of newborn neurons and their function, such as behavioral pattern separation, has remained puzzling. By analyzing a theoretical model, we show that the switch from excitation to inhibition of the GABAergic input onto maturing newborn cells is crucial for their proper functional integration. When the GABAergic input is excitatory, cooperativity drives the growth of synapses such that newborn cells become sensitive to stimuli similar to those that activate mature cells. When GABAergic input switches to inhibitory, competition pushes the configuration of synapses onto newborn cells toward stimuli that are different from previously stored ones. This enables the maturing newborn cells to code for concepts that are novel, yet similar to familiar ones. Our theory of newborn cell maturation explains both how adult-born dentate granule cells integrate into the preexisting network and why they promote separation of similar but not distinct patterns.


Assuntos
Giro Denteado , Modelos Neurológicos , Neurogênese/fisiologia , Animais , Animais Recém-Nascidos/fisiologia , Giro Denteado/citologia , Giro Denteado/crescimento & desenvolvimento , Neurônios GABAérgicos/citologia , Neurônios GABAérgicos/fisiologia , Interneurônios/citologia , Interneurônios/fisiologia , Rede Nervosa/citologia , Rede Nervosa/fisiologia , Roedores , Sinapses/fisiologia
11.
Nat Commun ; 12(1): 2859, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001873

RESUMO

The basolateral amygdalar complex (BLA) is implicated in behaviors ranging from fear acquisition to addiction. Optogenetic methods have enabled the association of circuit-specific functions to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted. Here, we apply machine-learning based computational and informatics analysis techniques to the results of circuit-tracing experiments to create a foundational, comprehensive BLA connectivity map. The analyses identify three distinct domains within the anterior BLA (BLAa) that house target-specific projection neurons with distinguishable morphological features. We identify brain-wide targets of projection neurons in the three BLAa domains, as well as in the posterior BLA, ventral BLA, posterior basomedial, and lateral amygdalar nuclei. Inputs to each nucleus also are identified via retrograde tracing. The data suggests that connectionally unique, domain-specific BLAa neurons are associated with distinct behavior networks.


Assuntos
Potenciais de Ação/fisiologia , Complexo Nuclear Basolateral da Amígdala/fisiologia , Medo/fisiologia , Rede Nervosa/fisiologia , Neurônios/fisiologia , Algoritmos , Animais , Complexo Nuclear Basolateral da Amígdala/citologia , Medo/psicologia , Feminino , Masculino , Camundongos Endogâmicos C57BL , Modelos Neurológicos , Rede Nervosa/citologia , Optogenética/métodos
12.
Nat Commun ; 12(1): 2143, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33837210

RESUMO

Spiking neural networks (SNNs) promise to bridge the gap between artificial neural networks (ANNs) and biological neural networks (BNNs) by exploiting biologically plausible neurons that offer faster inference, lower energy expenditure, and event-driven information processing capabilities. However, implementation of SNNs in future neuromorphic hardware requires hardware encoders analogous to the sensory neurons, which convert external/internal stimulus into spike trains based on specific neural algorithm along with inherent stochasticity. Unfortunately, conventional solid-state transducers are inadequate for this purpose necessitating the development of neural encoders to serve the growing need of neuromorphic computing. Here, we demonstrate a biomimetic device based on a dual gated MoS2 field effect transistor (FET) capable of encoding analog signals into stochastic spike trains following various neural encoding algorithms such as rate-based encoding, spike timing-based encoding, and spike count-based encoding. Two important aspects of neural encoding, namely, dynamic range and encoding precision are also captured in our demonstration. Furthermore, the encoding energy was found to be as frugal as ≈1-5 pJ/spike. Finally, we show fast (≈200 timesteps) encoding of the MNIST data set using our biomimetic device followed by more than 91% accurate inference using a trained SNN.


Assuntos
Materiais Biomiméticos , Redes Neurais de Computação , Transistores Eletrônicos , Potenciais de Ação/fisiologia , Algoritmos , Biomimética/instrumentação , Conjuntos de Dados como Assunto , Humanos , Rede Nervosa/citologia , Rede Nervosa/fisiologia , Células Receptoras Sensoriais/fisiologia , Córtex Visual/citologia , Córtex Visual/fisiologia
13.
Commun Biol ; 4(1): 275, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658641

RESUMO

The synaptic-tagging-and-capture (STC) hypothesis formulates that at each synapse the concurrence of a tag with protein synthesis yields the maintenance of changes induced by synaptic plasticity. This hypothesis provides a biological principle underlying the synaptic consolidation of memories that is not verified for recurrent neural circuits. We developed a theoretical model integrating the mechanisms underlying the STC hypothesis with calcium-based synaptic plasticity in a recurrent spiking neural network. In the model, calcium-based synaptic plasticity yields the formation of strongly interconnected cell assemblies encoding memories, followed by consolidation through the STC mechanisms. Furthermore, we show for the first time that STC mechanisms modify the storage of memories such that after several hours memory recall is significantly improved. We identify two contributing processes: a merely time-dependent passive improvement, and an active improvement during recall. The described characteristics can provide a new principle for storing information in biological and artificial neural circuits.


Assuntos
Encéfalo/fisiologia , Sinalização do Cálcio , Consolidação da Memória , Rememoração Mental , Modelos Neurológicos , Rede Nervosa/fisiologia , Plasticidade Neuronal , Transmissão Sináptica , Encéfalo/citologia , Humanos , Rede Nervosa/citologia , Fatores de Tempo
14.
Commun Biol ; 4(1): 277, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33664456

RESUMO

The human cortex exhibits intrinsic neural timescales that shape a temporal hierarchy. Whether this temporal hierarchy follows the spatial hierarchy of its topography, namely the core-periphery organization, remains an open issue. Using magnetoencephalography data, we investigate intrinsic neural timescales during rest and task states; we measure the autocorrelation window in short (ACW-50) and, introducing a novel variant, long (ACW-0) windows. We demonstrate longer ACW-50 and ACW-0 in networks located at the core compared to those at the periphery with rest and task states showing a high ACW correlation. Calculating rest-task differences, i.e., subtracting the shared core-periphery organization, reveals task-specific ACW changes in distinct networks. Finally, employing kernel density estimation, machine learning, and simulation, we demonstrate that ACW-0 exhibits better prediction in classifying a region's time window as core or periphery. Overall, our findings provide fundamental insight into how the human cortex's temporal hierarchy converges with its spatial core-periphery hierarchy.


Assuntos
Córtex Cerebral/fisiologia , Rede Nervosa/fisiologia , Neurônios/fisiologia , Mapeamento Encefálico , Córtex Cerebral/citologia , Humanos , Aprendizado de Máquina , Magnetoencefalografia , Modelos Neurológicos , Rede Nervosa/citologia , Fatores de Tempo
15.
Phys Rev E ; 103(2-1): 022312, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33735974

RESUMO

We investigate the occurrence of synchronous population activities in a neuronal network composed of both excitatory and inhibitory neurons and equipped with short-term synaptic plasticity. The collective firing patterns with different macroscopic properties emerge visually with the change of system parameters, and most long-time collective evolution also shows periodic-like characteristics. We systematically discuss the pattern-formation dynamics on a microscopic level and find a lot of hidden features of the population activities. The bursty phase with power-law distributed avalanches is observed in which the population activity can be either entire or local periodic-like. In the purely spike-to-spike synchronous regime, the periodic-like phase emerges from the synchronous chaos after the backward period-doubling transition. The local periodic-like population activity and the synchronous chaotic activity show substantial trial-to-trial variability, which is unfavorable for neural code, while they are contrary to the stable periodic-like phases. We also show that the inhibitory neurons can promote the generation of cluster firing behavior and strong bursty collective firing activity by depressing the activities of postsynaptic neurons partially or wholly.


Assuntos
Modelos Neurológicos , Rede Nervosa/citologia , Rede Nervosa/fisiologia , Plasticidade Neuronal , Neurônios/citologia , Humanos
16.
Exp Neurol ; 341: 113689, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33745921

RESUMO

The poor endogenous recovery capacity and other impediments to reinstating sensorimotor or autonomic function after adult neurotrauma have perplexed modern neuroscientists, bioengineers, and physicians for over a century. However, despite limited improvement in options to mitigate acute pathophysiological sequalae, the past 20 years have witnessed marked progresses in developing efficacious rehabilitation strategies for chronic spinal cord and brain injuries. The achievement is mainly attributable to research advancements in elucidating neuroplastic mechanisms for the potential to enhance clinical prognosis. Innovative cross-disciplinary studies have established novel therapeutic targets, theoretical frameworks, and regiments to attain treatment efficacy. This Special Issue contained eight papers that described experimental and human data along with literature reviews regarding the essential roles of the conventionally undervalued factors in neural repair: systemic inflammation, neural-respiratory inflammasome axis, modulation of glutamatergic and monoaminergic neurotransmission, neurogenesis, nerve transfer, recovery neurobiology components, and the spinal cord learning, respiration and central pattern generator neurocircuits. The focus of this work was on how to induce functional recovery from manipulating these underpinnings through their interactions with secondary injury events, peripheral and supraspinal inputs, neuromusculoskeletal network, and interventions (i.e., activity training, pharmacological adjuncts, electrical stimulation, and multimodal neuromechanical, brain-computer interface [BCI] and robotic assistance [RA] devices). The evidence suggested that if key neurocircuits are therapeutically reactivated, rebuilt, and/or modulated under proper sensory feedback, neurological function (e.g., cognition, respiration, limb movement, locomotion, etc.) will likely be reanimated after neurotrauma. The efficacy can be optimized by individualizing multimodal rehabilitation treatments via BCI/RA-integrated drug administration and neuromechanical protheses.


Assuntos
Lesões Encefálicas Traumáticas/reabilitação , Rede Nervosa/fisiologia , Reabilitação Neurológica/métodos , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/reabilitação , Animais , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/fisiopatologia , Humanos , Rede Nervosa/citologia , Reabilitação Neurológica/tendências , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia
17.
J Neurosci ; 41(18): 4036-4059, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33731450

RESUMO

We have previously established that PV+ neurons and Npas1+ neurons are distinct neuron classes in the external globus pallidus (GPe): they have different topographical, electrophysiological, circuit, and functional properties. Aside from Foxp2+ neurons, which are a unique subclass within the Npas1+ class, we lack driver lines that effectively capture other GPe neuron subclasses. In this study, we examined the utility of Kcng4-Cre, Npr3-Cre, and Npy2r-Cre mouse lines (both males and females) for the delineation of GPe neuron subtypes. By using these novel driver lines, we have provided the most exhaustive investigation of electrophysiological studies of GPe neuron subtypes to date. Corroborating our prior studies, GPe neurons can be divided into two statistically distinct clusters that map onto PV+ and Npas1+ classes. By combining optogenetics and machine learning-based tracking, we showed that optogenetic perturbation of GPe neuron subtypes generated unique behavioral structures. Our findings further highlighted the dissociable roles of GPe neurons in regulating movement and anxiety-like behavior. We concluded that Npr3+ neurons and Kcng4+ neurons are distinct subclasses of Npas1+ neurons and PV+ neurons, respectively. Finally, by examining local collateral connectivity, we inferred the circuit mechanisms involved in the motor patterns observed with optogenetic perturbations. In summary, by identifying mouse lines that allow for manipulations of GPe neuron subtypes, we created new opportunities for interrogations of cellular and circuit substrates that can be important for motor function and dysfunction.SIGNIFICANCE STATEMENT Within the basal ganglia, the external globus pallidus (GPe) has long been recognized for its involvement in motor control. However, we lacked an understanding of precisely how movement is controlled at the GPe level as a result of its cellular complexity. In this study, by using transgenic and cell-specific approaches, we showed that genetically-defined GPe neuron subtypes have distinct roles in regulating motor patterns. In addition, the in vivo contributions of these neuron subtypes are in part shaped by the local, inhibitory connections within the GPe. In sum, we have established the foundation for future investigations of motor function and disease pathophysiology.


Assuntos
Globo Pálido/citologia , Globo Pálido/fisiologia , Atividade Motora/fisiologia , Neurônios/fisiologia , Animais , Ansiedade/psicologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Comportamento Animal , Fenômenos Biomecânicos , Fenômenos Eletrofisiológicos , Feminino , Aprendizado de Máquina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Rede Nervosa/citologia , Rede Nervosa/fisiologia , Proteínas do Tecido Nervoso/genética , Optogenética , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Receptores do Fator Natriurético Atrial/genética
18.
J Neurosci ; 41(6): 1119-1129, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568445

RESUMO

The ability to sense the world, process information, and navigate the environment depends on the assembly and continuous function of neural circuits in the brain. Within the past two decades, new technologies have rapidly advanced our understanding of how neural circuits are wired during development and how they are stably maintained, often for years. Electron microscopy reconstructions of model organism connectomes have provided a map of the stereotyped (and variable) connections in the brain; advanced light microscopy techniques have enabled direct observation of the cellular dynamics that underlie circuit construction and maintenance; transcriptomic and proteomic surveys of both developing and mature neurons have provided insights into the molecular and genetic programs governing circuit establishment and maintenance; and advanced genetic techniques have allowed for high-throughput discovery of wiring regulators. These tools have empowered scientists to rapidly generate and test hypotheses about how circuits establish and maintain connectivity. Thus, the set of principles governing circuit formation and maintenance have been expanded. These principles are discussed in this review.


Assuntos
Encéfalo/citologia , Encéfalo/fisiologia , Rede Nervosa/citologia , Rede Nervosa/fisiologia , Neurogênese/fisiologia , Neurônios/fisiologia , Animais , Conectoma/métodos , Humanos , Proteômica/métodos , Sinapses/fisiologia
19.
Neuron ; 109(7): 1188-1201.e7, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33577748

RESUMO

Proprioception is essential for behavior and provides a sense of our body movements in physical space. Proprioceptor organs are thought to be only in the periphery. Whether the central nervous system can intrinsically sense its own movement remains unclear. Here we identify a segmental organ of proprioception in the adult zebrafish spinal cord, which is embedded by intraspinal mechanosensory neurons expressing Piezo2 channels. These cells are late-born, inhibitory, commissural neurons with unique molecular and physiological profiles reflecting a dual sensory and motor function. The central proprioceptive organ locally detects lateral body movements during locomotion and provides direct inhibitory feedback onto rhythm-generating interneurons responsible for the central motor program. This dynamically aligns central pattern generation with movement outcome for efficient locomotion. Our results demonstrate that a central proprioceptive organ monitors self-movement using hybrid neurons that merge sensory and motor entities into a unified network.


Assuntos
Retroalimentação Sensorial/fisiologia , Movimento/fisiologia , Propriocepção/fisiologia , Peixe-Zebra/fisiologia , Animais , Geradores de Padrão Central/fisiologia , Feminino , Interneurônios/fisiologia , Canais Iônicos/fisiologia , Locomoção/fisiologia , Masculino , Mecanotransdução Celular , Neurônios Motores/fisiologia , Rede Nervosa/citologia , Rede Nervosa/fisiologia , RNA/genética , Células Receptoras Sensoriais/fisiologia , Medula Espinal/diagnóstico por imagem , Medula Espinal/fisiologia , Tomografia Computadorizada por Raios X , Proteínas de Peixe-Zebra/fisiologia
20.
PLoS Comput Biol ; 17(2): e1007831, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33556070

RESUMO

The stimulation of a single neuron in the rat somatosensory cortex can elicit a behavioral response. The probability of a behavioral response does not depend appreciably on the duration or intensity of a constant stimulation, whereas the response probability increases significantly upon injection of an irregular current. Biological mechanisms that can potentially suppress a constant input signal are present in the dynamics of both neurons and synapses and seem ideal candidates to explain these experimental findings. Here, we study a large network of integrate-and-fire neurons with several salient features of neuronal populations in the rat barrel cortex. The model includes cellular spike-frequency adaptation, experimentally constrained numbers and types of chemical synapses endowed with short-term plasticity, and gap junctions. Numerical simulations of this model indicate that cellular and synaptic adaptation mechanisms alone may not suffice to account for the experimental results if the local network activity is read out by an integrator. However, a circuit that approximates a differentiator can detect the single-cell stimulation with a reliability that barely depends on the length or intensity of the stimulus, but that increases when an irregular signal is used. This finding is in accordance with the experimental results obtained for the stimulation of a regularly-spiking excitatory cell.


Assuntos
Modelos Neurológicos , Córtex Somatossensorial/citologia , Córtex Somatossensorial/fisiologia , Potenciais de Ação/fisiologia , Animais , Biologia Computacional , Simulação por Computador , Estimulação Elétrica , Fenômenos Eletrofisiológicos , Junções Comunicantes/fisiologia , Rede Nervosa/citologia , Rede Nervosa/fisiologia , Redes Neurais de Computação , Neurônios/fisiologia , Ratos , Sinapses/fisiologia
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