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1.
Nat Neurosci ; 22(11): 1834-1843, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31636447

RESUMO

Learning drives behavioral adaptations necessary for survival. While plasticity of excitatory projection neurons during associative learning has been extensively studied, little is known about the contributions of local interneurons. Using fear conditioning as a model for associative learning, we found that behaviorally relevant, salient stimuli cause learning by tapping into a local microcircuit consisting of precisely connected subtypes of inhibitory interneurons. By employing deep-brain calcium imaging and optogenetics, we demonstrate that vasoactive intestinal peptide (VIP)-expressing interneurons in the basolateral amygdala are activated by aversive events and provide a mandatory disinhibitory signal for associative learning. Notably, VIP interneuron responses during learning are strongly modulated by expectations. Our findings indicate that VIP interneurons are a central component of a dynamic circuit motif that mediates adaptive disinhibitory gating to specifically learn about unexpected, salient events, thereby ensuring appropriate behavioral adaptations.


Assuntos
Aprendizagem por Associação/fisiologia , Interneurônios/fisiologia , Inibição Neural/fisiologia , Filtro Sensorial/fisiologia , Peptídeo Intestinal Vasoativo/fisiologia , Tonsila do Cerebelo/fisiologia , Animais , Medo/psicologia , Feminino , Masculino , Camundongos , Camundongos Transgênicos , Optogenética
2.
Nat Commun ; 10(1): 4796, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31641138

RESUMO

Interneurons (INs) coordinate motoneuron activity to generate appropriate patterns of muscle contractions, providing animals with the ability to adjust their body posture and to move over a range of speeds. In Drosophila larvae several IN subtypes have been morphologically described and their function well documented. However, the general lack of molecular characterization of those INs prevents the identification of evolutionary counterparts in other animals, limiting our understanding of the principles underlying neuronal circuit organization and function. Here we characterize a restricted subset of neurons in the nerve cord expressing the Maf transcription factor Traffic Jam (TJ). We found that TJ+ neurons are highly diverse and selective activation of these different subtypes disrupts larval body posture and induces specific locomotor behaviors. Finally, we show that a small subset of TJ+ GABAergic INs, singled out by the expression of a unique transcription factors code, controls larval crawling speed.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila/fisiologia , Interneurônios/fisiologia , Fatores de Transcrição Maf Maior/metabolismo , Atividade Motora/fisiologia , Proteínas Proto-Oncogênicas/metabolismo , Animais , Animais Geneticamente Modificados , Drosophila/embriologia , Proteínas de Drosophila/genética , Embrião não Mamífero/fisiologia , Regulação da Expressão Gênica , Inativação Gênica , Larva/fisiologia , Locomoção/fisiologia , Fatores de Transcrição Maf Maior/genética , Proteínas Proto-Oncogênicas/genética , Raízes Nervosas Espinhais/fisiologia , Ácido gama-Aminobutírico/metabolismo
3.
PLoS Biol ; 17(9): e3000419, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31483783

RESUMO

Parvalbumin (PV)-positive interneurons modulate cortical activity through highly specialized connectivity patterns onto excitatory pyramidal neurons (PNs) and other inhibitory cells. PV cells are autoconnected through powerful autapses, but the contribution of this form of fast disinhibition to cortical function is unknown. We found that autaptic transmission represents the most powerful inhibitory input of PV cells in neocortical layer V. Autaptic strength was greater than synaptic strength onto PNs as a result of a larger quantal size, whereas autaptic and heterosynaptic PV-PV synapses differed in the number of release sites. Overall, single-axon autaptic transmission contributed to approximately 40% of the global inhibition (mostly perisomatic) that PV interneurons received. The strength of autaptic transmission modulated the coupling of PV-cell firing with optogenetically induced γ-oscillations, preventing high-frequency bursts of spikes. Autaptic self-inhibition represents an exceptionally large and fast disinhibitory mechanism, favoring synchronization of PV-cell firing during cognitive-relevant cortical network activity.


Assuntos
Interneurônios/fisiologia , Neocórtex/fisiologia , Sinapses , Transmissão Sináptica , Animais , Feminino , Masculino , Camundongos Endogâmicos C57BL
4.
Elife ; 82019 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-31545165

RESUMO

Enhancers are the primary DNA regulatory elements that confer cell type specificity of gene expression. Recent studies characterizing individual enhancers have revealed their potential to direct heterologous gene expression in a highly cell-type-specific manner. However, it has not yet been possible to systematically identify and test the function of enhancers for each of the many cell types in an organism. We have developed PESCA, a scalable and generalizable method that leverages ATAC- and single-cell RNA-sequencing protocols, to characterize cell-type-specific enhancers that should enable genetic access and perturbation of gene function across mammalian cell types. Focusing on the highly heterogeneous mammalian cerebral cortex, we apply PESCA to find enhancers and generate viral reagents capable of accessing and manipulating a subset of somatostatin-expressing cortical interneurons with high specificity. This study demonstrates the utility of this platform for developing new cell-type-specific viral reagents, with significant implications for both basic and translational research.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Biologia Molecular/métodos , Neurônios/efeitos dos fármacos , Neurofisiologia/métodos , Proteínas Recombinantes/biossíntese , Somatostatina/metabolismo , Vírus/genética , Animais , Animais Geneticamente Modificados , Córtex Cerebral/fisiologia , Genes Reguladores , Vetores Genéticos , Interneurônios/fisiologia , Camundongos , Proteínas Recombinantes/genética
5.
Nat Commun ; 10(1): 3664, 2019 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-31413258

RESUMO

Interneurons are critical for the proper functioning of neural circuits. While often morphologically complex, their dendrites have been ignored for decades, treating them as linear point neurons. Exciting new findings reveal complex, non-linear dendritic computations that call for a new theory of interneuron arithmetic. Using detailed biophysical models, we predict that dendrites of FS basket cells in both hippocampus and prefrontal cortex come in two flavors: supralinear, supporting local sodium spikes within large-volume branches and sublinear, in small-volume branches. Synaptic activation of varying sets of these dendrites leads to somatic firing variability that cannot be fully explained by the point neuron reduction. Instead, a 2-stage artificial neural network (ANN), with sub- and supralinear hidden nodes, captures most of the variance. Reduced neuronal circuit modeling suggest that this bi-modal, 2-stage integration in FS basket cells confers substantial resource savings in memory encoding as well as the linking of memories across time.


Assuntos
Dendritos/fisiologia , Sinapses Elétricas/fisiologia , Interneurônios/fisiologia , Hipocampo/citologia , Memória de Longo Prazo , Modelos Neurológicos , Córtex Pré-Frontal/citologia
6.
Nat Neurosci ; 22(10): 1709-1717, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31451803

RESUMO

Nervous system function relies on complex assemblies of distinct neuronal cell types that have unique anatomical and functional properties instructed by molecular programs. Alternative splicing is a key mechanism for the expansion of molecular repertoires, and protein splice isoforms shape neuronal cell surface recognition and function. However, the logic of how alternative splicing programs are arrayed across neuronal cells types is poorly understood. We systematically mapped ribosome-associated transcript isoforms in genetically defined neuron types of the mouse forebrain. Our dataset provides an extensive resource of transcript diversity across major neuron classes. We find that neuronal transcript isoform profiles reliably distinguish even closely related classes of pyramidal cells and inhibitory interneurons in the mouse hippocampus and neocortex. These highly specific alternative splicing programs selectively control synaptic proteins and intrinsic neuronal properties. Thus, transcript diversification via alternative splicing is a central mechanism for the functional specification of neuronal cell types and circuits.


Assuntos
Processamento Alternativo/genética , Neurônios/fisiologia , Ribossomos/genética , Transcrição Genética/genética , Animais , Células Cultivadas , Feminino , Regulação da Expressão Gênica/genética , Hipocampo/citologia , Interneurônios/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neocórtex/citologia , Neurônios/classificação , Terminações Pré-Sinápticas/metabolismo , Prosencéfalo/citologia , Isoformas de Proteínas/genética , Células Piramidais/fisiologia
7.
Elife ; 82019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31453803

RESUMO

Lineage regulates the synaptic connections between neurons in some regions of the invertebrate nervous system. In mammals, recent experiments suggest that cell lineage determines the connectivity of pyramidal neurons in the neocortex, but the functional relevance of this phenomenon and whether it occurs in other neuronal types remains controversial. We investigated whether lineage plays a role in the connectivity of mitral and tufted cells, the projection neurons in the mouse olfactory bulb. We used transgenic mice to sparsely label neuronal progenitors and observed that clonally related neurons receive synaptic input from olfactory sensory neurons expressing different olfactory receptors. These results indicate that lineage does not determine the connectivity between olfactory sensory neurons and olfactory bulb projection neurons.


Assuntos
Interneurônios/fisiologia , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Bulbo Olfatório/anatomia & histologia , Bulbo Olfatório/fisiologia , Neurônios Receptores Olfatórios/fisiologia , Animais , Camundongos , Camundongos Transgênicos
8.
PLoS Comput Biol ; 15(7): e1007106, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31295266

RESUMO

Experimental studies show that human pain sensitivity varies across the 24-hour day, with the lowest sensitivity usually occurring during the afternoon. Patients suffering from neuropathic pain, or nerve damage, experience an inversion in the daily modulation of pain sensitivity, with the highest sensitivity usually occurring during the early afternoon. Processing of painful stimulation occurs in the dorsal horn (DH), an area of the spinal cord that receives input from peripheral tissues via several types of primary afferent nerve fibers. The DH circuit is composed of different populations of neurons, including excitatory and inhibitory interneurons, and projection neurons, which constitute the majority of the output from the DH to the brain. In this work, we develop a mathematical model of the dorsal horn neural circuit to investigate mechanisms for the daily modulation of pain sensitivity. The model describes average firing rates of excitatory and inhibitory interneuron populations and projection neurons, whose activity is directly correlated with experienced pain. Response in afferent fibers to peripheral stimulation is simulated by a Poisson process generating nerve fiber spike trains at variable firing rates. Model parameters for fiber response to stimulation and the excitability properties of neuronal populations are constrained by experimental results found in the literature, leading to qualitative agreement between modeled responses to pain and experimental observations. We validate our model by reproducing the wind-up of pain response to repeated stimulation. We apply the model to investigate daily modulatory effects on pain inhibition, in which response to painful stimuli is reduced by subsequent non-painful stimuli. Finally, we use the model to propose a mechanism for the observed inversion of the daily rhythmicity of pain sensation under neuropathic pain conditions. Underlying mechanisms for the shift in rhythmicity have not been identified experimentally, but our model results predict that experimentally-observed dysregulation of inhibition within the DH neural circuit may be responsible. The model provides an accessible, biophysical framework that will be valuable for experimental and clinical investigations of diverse physiological processes modulating pain processing in humans.


Assuntos
Ritmo Circadiano/fisiologia , Modelos Neurológicos , Dor/fisiopatologia , Corno Dorsal da Medula Espinal/fisiopatologia , Biologia Computacional , Gânglios Espinais/fisiopatologia , Humanos , Interneurônios/fisiologia , Rede Nervosa/fisiologia , Neuralgia/fisiopatologia , Nociceptividade/fisiologia , Dor Nociceptiva/fisiopatologia , Percepção da Dor/fisiologia
9.
Nat Neurosci ; 22(8): 1357-1370, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31285615

RESUMO

The medial prefrontal cortex (mPFC) contains populations of GABAergic interneurons that play different roles in cognition and emotion. Their local and long-range inputs are incompletely understood. We used monosynaptic rabies viral tracers in combination with fluorescence micro-optical sectioning tomography to generate a whole-brain atlas of direct long-range inputs to GABAergic interneurons in the mPFC of male mice. We discovered that three subtypes of GABAergic interneurons in two areas of the mPFC are innervated by same upstream areas. Input from subcortical upstream areas includes cholinergic neurons from the basal forebrain and serotonergic neurons (which co-release glutamate) from the raphe nuclei. Reconstruction of single-neuron morphology revealed novel substantia innominata-anteromedial thalamic nucleus-mPFC and striatum-anteromedial thalamic nucleus-mPFC circuits. Based on the projection logic of individual neurons, we classified cortical and hippocampal input neurons into several types. This atlas provides the anatomical foundation for understanding the functional organization of the mPFC.


Assuntos
Mapeamento Encefálico/métodos , Interneurônios/fisiologia , Córtex Pré-Frontal/anatomia & histologia , Córtex Pré-Frontal/citologia , Ácido gama-Aminobutírico/fisiologia , Animais , Contagem de Células , Hipocampo/citologia , Hipocampo/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sistema Nervoso Parassimpático/citologia , Sistema Nervoso Parassimpático/fisiologia , Prosencéfalo/anatomia & histologia , Prosencéfalo/citologia , Núcleos da Rafe/citologia , Núcleos da Rafe/fisiologia , Neurônios Serotoninérgicos/fisiologia , Tálamo/citologia , Tálamo/fisiologia
10.
Brain Stimul ; 12(6): 1490-1499, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31289014

RESUMO

BACKGROUND: Cortical oscillatory activities play a role in regulating several brain functions in humans. However, whether motor resonant oscillations (i.e. ß and γ) modulate long-term depression (LTD)-like plasticity of the primary motor cortex (M1) is still unclear. OBJECTIVE: To address this issue, we combined transcranial alternating current stimulation (tACS), a technique able to entrain cortical oscillations, with continuous theta burst stimulation (cTBS), a transcranial magnetic stimulation (TMS) protocol commonly used to induce LTD-like plasticity in M1. METHODS: Motor evoked potentials (MEPs) elicited by single-pulse TMS, short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were evaluated before and 5, 15 and 30 min after cTBS alone or cTBS delivered during ß-tACS (cTBS-ß) or γ-tACS (cTBS-γ). Moreover, we tested the effects of ß-tACS (alone) on short-latency afferent inhibition (SAI) and γ-tACS on SICI in order to verify whether tACS-related interneuronal modulation contributes to the effects of tACS-cTBS co-stimulation. RESULTS: cTBS-γ turned the expected after-effects of cTBS from inhibition to facilitation. By contrast, responses to cTBS-ß were similar to those induced by cTBS alone. ß- and γ-tACS did not change MEPs evoked by single-pulse TMS. ß-tACS reduced SAI and γ-tACS reduced SICI. However, the degree of γ-tACS-induced modulation of SICI did not correlate with the effects of cTBS-γ. CONCLUSION: γ-tACS reverses cTBS-induced plasticity of the human M1. γ-oscillations may therefore regulate LTD-like plasticity mechanisms.


Assuntos
Potencial Evocado Motor/fisiologia , Depressão Sináptica de Longo Prazo/fisiologia , Córtex Motor/fisiologia , Plasticidade Neuronal/fisiologia , Estimulação Transcraniana por Corrente Contínua/métodos , Adulto , Feminino , Humanos , Interneurônios/fisiologia , Masculino , Estimulação Magnética Transcraniana/métodos
11.
Genetics ; 213(1): 267-279, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31292211

RESUMO

Sleep is evolutionarily conserved, thus studying simple invertebrates such as Caenorhabditis elegans can provide mechanistic insight into sleep with single cell resolution. A conserved pathway regulating sleep across phylogeny involves cyclic adenosine monophosphate (cAMP), a ubiquitous second messenger that functions in neurons by activating protein kinase A. C. elegans sleep in response to cellular stress caused by environmental insults [stress-induced sleep (SIS)], a model for studying sleep during sickness. SIS is controlled by simple neural circuitry, thus allowing for cellular dissection of cAMP signaling during sleep. We employed a red-light activated adenylyl cyclase, IlaC22, to identify cells involved in SIS regulation. We found that pan-neuronal activation of IlaC22 disrupts SIS through mechanisms independent of the cAMP response element binding protein. Activating IlaC22 in the single DVA interneuron, the paired RIF interneurons, and in the CEPsh glia identified these cells as wake-promoting. Using a cAMP biosensor, epac1-camps, we found that cAMP is decreased in the RIF and DVA interneurons by neuropeptidergic signaling from the ALA neuron. Ectopic overexpression of sleep-promoting neuropeptides coded by flp-13 and flp-24, released from the ALA, reduced cAMP in the DVA and RIFs, respectively. Overexpression of the wake-promoting neuropeptides coded by pdf-1 increased cAMP levels in the RIFs. Using a combination of optogenetic manipulation and in vivo imaging of cAMP we have identified wake-promoting neurons downstream of the neuropeptidergic output of the ALA. Our data suggest that sleep- and wake-promoting neuropeptides signal to reduce and heighten cAMP levels during sleep, respectively.


Assuntos
AMP Cíclico/metabolismo , Interneurônios/metabolismo , Locomoção , Transdução de Sinais , Sono , Estresse Fisiológico , Adenilil Ciclases/genética , Adenilil Ciclases/metabolismo , Animais , Técnicas Biossensoriais/métodos , Caenorhabditis elegans , Interneurônios/fisiologia , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Optogenética/métodos
12.
Biomed Res Int ; 2019: 3426092, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281833

RESUMO

Anxiety is one of the most frequent psychiatric disorders. Despite the fact that most studies describe an anxiolytic effect of testosterone, hyperandrogenemia in mothers is assumed to be related to an increased risk of mood disorders in their offspring. An increasing body of scientific evidence suggests that an altered expression of interneuronal markers of the hippocampus may be the cause of anxiety. The aim of this study was to examine the influence of maternal hyperandrogenemia on behavioral parameters of anxiety-like behavior, neuropeptide Y (NPY) and parvalbumin (PV) expression in the hippocampus, and the level of the brain-derived neurotrophic factor (BDNF) in the hippocampus and cerebral cortex. Pregnant female Wistar albino rats were treated with testosterone undecanoate on the 20th day of gestation. Anxiety-like behavior in adult female offspring was evaluated by the elevated plus maze test and the open field. The number of PV and NPY immunoreactive cells in the hippocampus was determined immunohistochemically. The level of BDNF expression in the hippocampus and cerebral cortex was analyzed with the Western blot test. Prenatal hyperandrogenization increased anxiety-like behavior in female offspring and decreased expression of NPY+ and PV+ in the CA1 region of the hippocampus as compared to the control group. BDNF expression in the hippocampus and cerebral cortex of prenatally androgenized female offspring was significantly increased in comparison with the controls. Prenatal hyperandrogenization may be the cause of anxiety-like behavior in female offspring. Decrease in NPY and PV expression in the hippocampus may explain the possible mechanism of hyperandrogenization induced anxiety.


Assuntos
Ansiedade/etiologia , Comportamento Animal , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Interneurônios/fisiologia , Inibição Neural/fisiologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Virilismo/complicações , Animais , Ansiedade/sangue , Ansiedade/fisiopatologia , Estradiol/sangue , Feminino , Hipocampo/fisiopatologia , Aprendizagem em Labirinto , Neuropeptídeo Y/metabolismo , Parvalbuminas/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos Wistar , Testosterona/administração & dosagem , Testosterona/sangue , Testosterona/farmacologia , Virilismo/fisiopatologia
14.
Nat Commun ; 10(1): 3369, 2019 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358754

RESUMO

Inhibitory interneurons are integral to sensory processing, yet revealing their cell type-specific roles in sensory circuits remains an ongoing focus. To Investigate the mouse olfactory system, we selectively remove GABAergic transmission from a subset of olfactory bulb interneurons, EPL interneurons (EPL-INs), and assay odor responses from their downstream synaptic partners - tufted cells and mitral cells. Using a combination of in vivo electrophysiological and imaging analyses, we find that inactivating this single node of inhibition leads to differential effects in magnitude, reliability, tuning width, and temporal dynamics between the two principal neurons. Furthermore, tufted and not mitral cell responses to odor mixtures become more linearly predictable without EPL-IN inhibition. Our data suggest that olfactory bulb interneurons, through exerting distinct inhibitory functions onto their different synaptic partners, play a significant role in the processing of odor information.


Assuntos
Interneurônios/fisiologia , Inibição Neural/fisiologia , Neurônios/fisiologia , Bulbo Olfatório/fisiologia , Condutos Olfatórios/fisiologia , Animais , Interneurônios/citologia , Interneurônios/metabolismo , Camundongos Knockout , Camundongos Transgênicos , Inibição Neural/genética , Neurônios/citologia , Neurônios/metabolismo , Odorantes , Bulbo Olfatório/citologia , Bulbo Olfatório/metabolismo , Olfato , Transmissão Sináptica/genética , Transmissão Sináptica/fisiologia
15.
Elife ; 82019 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-31355747

RESUMO

The spinal cord contains a diverse array of interneurons that govern motor output. Traditionally, models of spinal circuits have emphasized the role of inhibition in enforcing reciprocal alternation between left and right sides or flexors and extensors. However, recent work has shown that inhibition also increases coincident with excitation during contraction. Here, using larval zebrafish, we investigate the V2b (Gata3+) class of neurons, which contribute to flexor-extensor alternation but are otherwise poorly understood. Using newly generated transgenic lines we define two stable subclasses with distinct neurotransmitter and morphological properties. These V2b subclasses synapse directly onto motor neurons with differential targeting to speed-specific circuits. In vivo, optogenetic manipulation of V2b activity modulates locomotor frequency: suppressing V2b neurons elicits faster locomotion, whereas activating V2b neurons slows locomotion. We conclude that V2b neurons serve as a brake on axial motor circuits. Together, these results indicate a role for ipsilateral inhibition in speed control.


Assuntos
Interneurônios/fisiologia , Neurônios Motores/fisiologia , Medula Espinal/citologia , Animais , Movimento (Física) , Contração Muscular , Peixe-Zebra
16.
Neuron ; 103(3): 432-444.e3, 2019 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-31221559

RESUMO

Subtypes of nucleus accumbens medium spiny neurons (MSNs) promote dichotomous outcomes in motivated behaviors. However, recent reports indicate enhancing activity of either nucleus accumbens (NAc) core MSN subtype augments reward, suggesting coincident MSN activity may underlie this outcome. Here, we report a collateral excitation mechanism in which high-frequency, NAc core dopamine 1 (D1)-MSN activation causes long-lasting potentiation of excitatory transmission (LLP) on dopamine receptor 2 (D2)-MSNs. Our mechanistic investigation demonstrates that this form of plasticity requires release of the excitatory peptide substance P from D1-MSNs and robust cholinergic interneuron activation through neurokinin receptor stimulation. We also reveal that D2-MSN LLP requires muscarinic 1 receptor activation, intracellular calcium signaling, and GluR2-lacking AMPAR insertion. This study uncovers a mechanism for shaping NAc core activity through the transfer of excitatory information from D1-MSNs to D2-MSNs and may provide a means for altering goal-directed behavior through coordinated MSN activity.


Assuntos
Neurônios Dopaminérgicos/fisiologia , Potenciação de Longa Duração/fisiologia , Núcleo Accumbens/fisiologia , Substância P/metabolismo , Potenciais de Ação/fisiologia , Animais , Aprepitanto/farmacologia , Sinalização do Cálcio/fisiologia , Neurônios Colinérgicos/fisiologia , Neurônios Dopaminérgicos/efeitos da radiação , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Interneurônios/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Motivação , Antagonistas do Receptor de Neuroquinina-1/farmacologia , Núcleo Accumbens/citologia , Estimulação Luminosa , Piperidinas/farmacologia , Receptor Muscarínico M1/fisiologia , Receptores de AMPA/fisiologia , Receptores de Dopamina D1/análise , Receptores de Dopamina D2/análise , Receptores da Neurocinina-1/fisiologia
17.
Nat Commun ; 10(1): 2715, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31222009

RESUMO

Most adaptive behaviors require precise tracking of targets in space. In pursuit behavior with a moving target, mice use distance to target to guide their own movement continuously. Here, we show that in the sensorimotor striatum, parvalbumin-positive fast-spiking interneurons (FSIs) can represent the distance between self and target during pursuit behavior, while striatal projection neurons (SPNs), which receive FSI projections, can represent self-velocity. FSIs are shown to regulate velocity-related SPN activity during pursuit, so that movement velocity is continuously modulated by distance to target. Moreover, bidirectional manipulation of FSI activity can selectively disrupt performance by increasing or decreasing the self-target distance. Our results reveal a key role of the FSI-SPN interneuron circuit in pursuit behavior and elucidate how this circuit implements distance to velocity transformation required for the critical underlying computation.


Assuntos
Corpo Estriado/fisiologia , Interneurônios/fisiologia , Locomoção/fisiologia , Animais , Técnicas de Observação do Comportamento/métodos , Corpo Estriado/citologia , Corpo Estriado/diagnóstico por imagem , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Rede Nervosa/fisiologia , Imagem Óptica , Comportamento Predatório/fisiologia , Comportamento Sexual Animal/fisiologia
18.
Nat Commun ; 10(1): 2533, 2019 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182715

RESUMO

Spatiotemporally synchronised neuronal activity is central to sensation, motion and cognition. Brain circuits consist of dynamically interconnected neuronal cell-types, thus elucidating how neuron types synergise within the network is key to understand the neuronal orchestra. Here we show that in neocortex neuron-network coupling is neuronal cell-subtype specific. Employing in vivo two-photon (2-p) Calcium (Ca) imaging and 2-p targeted whole-cell recordings, we cell-type specifically investigated the coupling profiles of genetically defined neuron populations in superficial layers (L) of mouse primary visual cortex (V1). Our data reveal novel subtlety of neuron-network coupling in inhibitory interneurons (INs). Parvalbumin (PV)- and Vasoactive intestinal peptide (VIP)-expressing INs exhibit skewed distributions towards strong network-coupling; in Somatostatin (SST)-expressing INs, however, two physiological subpopulations are identified with distinct neuron-network coupling profiles, providing direct evidence for subtype specificity. Our results thus add novel functional granularity to neuronal cell-typing, and provided insights critical to simplifying/understanding neural dynamics.


Assuntos
Interneurônios/fisiologia , Neurônios/fisiologia , Córtex Visual/citologia , Córtex Visual/fisiologia , Animais , Cálcio/metabolismo , Eletrofisiologia , Potenciais Evocados Visuais , Feminino , Masculino , Camundongos Transgênicos , Microscopia de Fluorescência por Excitação Multifotônica , Parvalbuminas/metabolismo , Estimulação Luminosa , Somatostatina/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo
19.
Nat Neurosci ; 22(7): 1168-1181, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31235906

RESUMO

The hippocampus is able to rapidly learn incoming information, even if that information is only observed once. Furthermore, this information can be replayed in a compressed format in either forward or reverse modes during sharp wave-ripples (SPW-Rs). We leveraged state-of-the-art techniques in training recurrent spiking networks to demonstrate how primarily interneuron networks can achieve the following: (1) generate internal theta sequences to bind externally elicited spikes in the presence of inhibition from the medial septum; (2) compress learned spike sequences in the form of a SPW-R when septal inhibition is removed; (3) generate and refine high-frequency assemblies during SPW-R-mediated compression; and (4) regulate the inter-SPW interval timing between SPW-Rs in ripple clusters. From the fast timescale of neurons to the slow timescale of behaviors, interneuron networks serve as the scaffolding for one-shot learning by replaying, reversing, refining, and regulating spike sequences.


Assuntos
Região CA3 Hipocampal/fisiologia , Simulação por Computador , Interneurônios/fisiologia , Aprendizagem/fisiologia , Plasticidade Neuronal/fisiologia , Memória/fisiologia , Núcleos Septais/fisiologia , Fatores de Tempo
20.
Front Neural Circuits ; 13: 40, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31191259

RESUMO

The mouse primary visual cortex (V1) has become an important brain area for exploring how neural circuits process information. Optogenetic tools have helped to outline the connectivity of a local V1 circuit comprising excitatory pyramidal neurons and several genetically-defined inhibitory interneuron subtypes that express parvalbumin, somatostatin, or vasoactive intestinal peptide. Optogenetic modulation of individual interneuron subtypes can alter the visual responsiveness of pyramidal neurons with distinct forms of inhibition and disinhibition. However, different interneuron subtypes have potentially opposing actions, and the potency of their effects relative to each other remains unclear. Therefore, in this study we simultaneously optogenetically activated all interneuron subtypes during visual processing to explore whether any single inhibitory effect would predominate. This aggregate interneuron activation consistently inhibited pyramidal neurons in a divisive manner, which was essentially identical to the pattern of inhibition produced by activating parvalbumin-expressing interneurons alone.


Assuntos
Interneurônios/fisiologia , Inibição Neural/fisiologia , Córtex Visual/fisiologia , Percepção Visual/fisiologia , Animais , Camundongos , Camundongos Transgênicos , Optogenética , Células Piramidais/fisiologia
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