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1.
Cereb Cortex ; 21(3): 666-82, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20705896

RESUMO

Fast-spiking (FS) cells are a prominent subtype of neocortical γ-aminobutyric acidergic interneurons that mediate feed-forward inhibition and the temporal sculpting of information transfer in neural circuits, maintain excitation/inhibition balance, and contribute to network oscillations. FS cell dysfunction may be involved in the pathogenesis of disorders such as epilepsy, autism, and schizophrenia. Mature FS cells exhibit coordinated molecular and cellular specializations that facilitate rapid responsiveness, including brief spikes and sustained high-frequency discharge. We show that these features appear during the second and third postnatal weeks driven by upregulation of K(+) channel subunits of the Kv3 subfamily. The low membrane resistance and fast time constant characteristic of FS cells also appears during this time, driven by expression of a K(+) leak current mediated by K(ir)2 subfamily inward rectifier K(+) channels and TASK subfamily 2-pore K(+) channels. Blockade of this leak produces dramatic depolarization of FS cells suggesting the possibility for potent neuromodulation. Finally, the frequency of FS cell membrane potential oscillations increases during development and is markedly slower in TASK-1/3 knockout mice, suggesting that TASK channels regulate FS cell rhythmogenesis. Our findings imply that some of the effects of acidosis and/or anesthetics on brain function may be due to blockade of TASK channels in FS cells.


Assuntos
Interneurônios/citologia , Neocórtex/crescimento & desenvolvimento , Proteínas do Tecido Nervoso/metabolismo , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Animais , Western Blotting , Separação Celular , Citometria de Fluxo , Imuno-Histoquímica , Camundongos , Camundongos Knockout , Proteínas do Tecido Nervoso/deficiência , Neurogênese/fisiologia , Técnicas de Cultura de Órgãos , Técnicas de Patch-Clamp , Canais de Potássio de Domínios Poros em Tandem/deficiência , Reação em Cadeia da Polimerase Via Transcriptase Reversa
2.
Elife ; 92020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33355093

RESUMO

The basal forebrain cholinergic system projects broadly throughout the cortex and constitutes a critical source of neuromodulation for arousal and attention. Traditionally, this system was thought to function diffusely. However, recent studies have revealed a high degree of spatiotemporal specificity in cholinergic signaling. How the organization of cholinergic afferents confers this level of precision remains unknown. Here, using intersectional genetic fate mapping, we demonstrate that cholinergic fibers within the mouse cortex exhibit remarkable laminar and regional specificity and that this is organized in accordance with cellular birthdate. Strikingly, birthdated cholinergic projections within the cortex follow an inside-out pattern of innervation. While early born cholinergic populations target deep layers, late born ones innervate superficial laminae. We also find that birthdate predicts cholinergic innervation patterns within the amygdala, hippocampus, and prefrontal cortex. Our work reveals previously unappreciated specificity within the cholinergic system and the developmental logic by which these circuits are assembled.


Assuntos
Prosencéfalo Basal/fisiologia , Neurônios Colinérgicos/fisiologia , Fatores Etários , Animais , Prosencéfalo Basal/anatomia & histologia , Mapeamento Encefálico , Feminino , Masculino , Camundongos , Camundongos Endogâmicos , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Córtex Somatossensorial/anatomia & histologia , Córtex Somatossensorial/fisiologia
3.
Neuron ; 106(5): 842-854.e4, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32213321

RESUMO

Excitation in neural circuits must be carefully controlled by inhibition to regulate information processing and network excitability. During development, cortical inhibitory and excitatory inputs are initially mismatched but become co-tuned or balanced with experience. However, little is known about how excitatory-inhibitory balance is defined at most synapses or about the mechanisms for establishing or maintaining this balance at specific set points. Here we show how coordinated long-term plasticity calibrates populations of excitatory-inhibitory inputs onto mouse auditory cortical pyramidal neurons. Pairing pre- and postsynaptic activity induced plasticity at paired inputs and different forms of heterosynaptic plasticity at the strongest unpaired synapses, which required minutes of activity and dendritic Ca2+ signaling to be computed. Theoretical analyses demonstrated how the relative rate of heterosynaptic plasticity could normalize and stabilize synaptic strengths to achieve any possible excitatory-inhibitory correlation. Thus, excitatory-inhibitory balance is dynamic and cell specific, determined by distinct plasticity rules across multiple excitatory and inhibitory synapses.


Assuntos
Potenciais de Ação/fisiologia , Córtex Auditivo/fisiologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciais Pós-Sinápticos Inibidores/fisiologia , Inibição Neural/fisiologia , Plasticidade Neuronal/fisiologia , Células Piramidais/fisiologia , Animais , Sinalização do Cálcio , Potenciais Evocados , Potenciação de Longa Duração/fisiologia , Camundongos , Técnicas de Patch-Clamp , Sinapses/fisiologia
4.
Neurosci Lett ; 433(2): 129-34, 2008 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-18276073

RESUMO

Anatomical and imaging studies show ample evidence for auditory activation of the visual cortex following early onset of blindness in both humans and animal models. Anatomical studies in animal models of early blindness clearly show intermodal pathways through which auditory information can reach the primary visual cortex. There is clear evidence for intermodal corticocortical pathways linking auditory and visual cortex and also novel connections between the inferior colliculus and the visual thalamus. A recent publication [L.K. Laemle, N.L. Strominger, D.O. Carpenter, Cross-modal innervation of primary visual cortex by auditory fibers in congenitally anophthalmic mice, Neurosci. Lett. 396 (2006) 108-112] suggested the presence of a direct reciprocal connection between the inferior colliculus and the primary visual cortex (V1) in congenitally anophthalmic ZRDCT/An mice. This implies that this mutant mouse would be the only known vertebrate having a direct tectal connection with a primary sensory cortex. The presence of this peculiar pathway was reinvestigated in the ZRDCT/An mouse with highly sensitive neuronal tracers. We found the connections normally described in the ZRDCT/An mouse between: (i) the inferior colliculus and the dorsal lateral geniculate nucleus, (ii) V1 and the superior colliculus, (iii) the lateral posterior nucleus and V1 and between (iv) the inferior colliculus and the medial geniculate nucleus. We also show unambiguously that the auditory subcortical structures do not connect the primary visual cortex in the anophthalmic mouse. In particular, we find no evidence of a direct projection from the auditory mesencephalon to the cortex in this animal model of blindness.


Assuntos
Anoftalmia/patologia , Vias Auditivas/patologia , Mapeamento Encefálico , Tálamo/patologia , Córtex Visual/patologia , Animais , Vias Auditivas/fisiopatologia , Biotina/análogos & derivados , Biotina/metabolismo , Dextranos/metabolismo , Camundongos , Camundongos Mutantes Neurológicos
5.
Science ; 355(6328): 954-959, 2017 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-28254942

RESUMO

γ-Aminobutyric acid (GABA)ergic inputs are strategically positioned to gate synaptic integration along the dendritic arbor of pyramidal cells. However, their spatiotemporal dynamics during behavior are poorly understood. Using an optical-tagging electrophysiological approach to record and label somatostatin-expressing (Sst) interneurons (GABAergic neurons specialized for dendritic inhibition), we discovered a layer-specific modulation of their activity in behaving mice. Sst interneuron subtypes, residing in different cortical layers and innervating complementary laminar domains, exhibited opposite activity changes during transitions to active wakefulness. The relative weight of vasoactive intestinal peptide-expressing (Vip) interneuron-mediated inhibition of distinct Sst interneurons and cholinergic modulation determined their in vivo activity. These results reveal a state-dependent laminar influence of Sst interneuron-mediated inhibition, with implications for the compartmentalized regulation of dendritic signaling in the mammalian neocortex.


Assuntos
Dendritos/fisiologia , Neurônios GABAérgicos/fisiologia , Interneurônios/fisiologia , Neocórtex/fisiologia , Inibição Neural , Vigília/fisiologia , Acetilcolina/metabolismo , Animais , Comportamento , Feminino , Neurônios GABAérgicos/metabolismo , Interneurônios/metabolismo , Masculino , Camundongos , Camundongos Knockout , Neocórtex/citologia , Células Piramidais/fisiologia , Receptores Muscarínicos/metabolismo , Somatostatina/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo , Ácido gama-Aminobutírico/metabolismo
6.
Nat Neurosci ; 20(11): 1580-1590, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28920934

RESUMO

As an essential means of resolving conflicts, aggression is expressed by both sexes but often at a higher level in males than in females. Recent studies suggest that cells in the ventrolateral part of the ventromedial hypothalamus (VMHvl) that express estrogen receptor-α (Esr1) and progesterone receptor are essential for male but not female mouse aggression. In contrast, here we show that VMHvlEsr1+ cells are indispensable for female aggression. This population was active when females attacked naturally. Inactivation of these cells reduced female aggression whereas their activation elicited attack. Additionally, we found that female VMHvl contains two anatomically distinguishable subdivisions that showed differential gene expression, projection and activation patterns after mating and fighting. These results support an essential role of the VMHvl in both male and female aggression and reveal the existence of two previously unappreciated subdivisions in the female VMHvl that are involved in distinct social behaviors.


Assuntos
Agressão/fisiologia , Receptor alfa de Estrogênio/biossíntese , Comportamento Sexual Animal/fisiologia , Núcleo Hipotalâmico Ventromedial/citologia , Núcleo Hipotalâmico Ventromedial/metabolismo , Agressão/psicologia , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/metabolismo
7.
Neuron ; 91(2): 260-92, 2016 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-27477017

RESUMO

Cortical networks are composed of glutamatergic excitatory projection neurons and local GABAergic inhibitory interneurons that gate signal flow and sculpt network dynamics. Although they represent a minority of the total neocortical neuronal population, GABAergic interneurons are highly heterogeneous, forming functional classes based on their morphological, electrophysiological, and molecular features, as well as connectivity and in vivo patterns of activity. Here we review our current understanding of neocortical interneuron diversity and the properties that distinguish cell types. We then discuss how the involvement of multiple cell types, each with a specific set of cellular properties, plays a crucial role in diversifying and increasing the computational power of a relatively small number of simple circuit motifs forming cortical networks. We illustrate how recent advances in the field have shed light onto the mechanisms by which GABAergic inhibition contributes to network operations.


Assuntos
Diferenciação Celular/fisiologia , Interneurônios/fisiologia , Neocórtex/metabolismo , Rede Nervosa/fisiologia , Inibição Neural/fisiologia , Animais , Humanos , Ácido gama-Aminobutírico/metabolismo
8.
Nat Neurosci ; 19(12): 1743-1749, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27798629

RESUMO

A fundamental impediment to understanding the brain is the availability of inexpensive and robust methods for targeting and manipulating specific neuronal populations. The need to overcome this barrier is pressing because there are considerable anatomical, physiological, cognitive and behavioral differences between mice and higher mammalian species in which it is difficult to specifically target and manipulate genetically defined functional cell types. In particular, it is unclear the degree to which insights from mouse models can shed light on the neural mechanisms that mediate cognitive functions in higher species, including humans. Here we describe a novel recombinant adeno-associated virus that restricts gene expression to GABAergic interneurons within the telencephalon. We demonstrate that the viral expression is specific and robust, allowing for morphological visualization, activity monitoring and functional manipulation of interneurons in both mice and non-genetically tractable species, thus opening the possibility to study GABAergic function in virtually any vertebrate species.


Assuntos
Encéfalo/virologia , Dependovirus/isolamento & purificação , Neurônios GABAérgicos/virologia , Interneurônios/fisiologia , Vertebrados/virologia , Animais , Comportamento Animal , Encéfalo/metabolismo , Células Cultivadas , Dependovirus/genética , Feminino , Neurônios GABAérgicos/patologia , Vetores Genéticos/genética , Camundongos Endogâmicos C57BL
9.
Cell Rep ; 9(6): 2304-16, 2014 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-25533350

RESUMO

Brain networks contain a large diversity of functionally distinct neuronal elements, each with unique properties, enabling computational capacities and supporting brain functions. Understanding their functional implications for behavior requires the precise identification of the cell types of a network and in vivo monitoring of their activity profiles. Here, we developed a channelrhodopsin-assisted patching method allowing the efficient in vivo targeted recording of neurons identified by their molecular, electrophysiological, and morphological features. The method has a high yield, does not require visual guidance, and thus can be applied at any depth in the brain. This approach overcomes limitations of present technologies. We validate this strategy with in vivo recordings of identified subtypes of GABAergic and glutamatergic neurons in deep cortical layers, subcortical cholinergic neurons, and neurons in the thalamic reticular nucleus in anesthetized and awake mice. We propose this method as an important complement to existing technologies to relate specific cell-type activity to brain circuitry, function, and behavior.


Assuntos
Encéfalo/fisiologia , Neurônios GABAérgicos/fisiologia , Optogenética/métodos , Técnicas de Patch-Clamp/métodos , Animais , Encéfalo/citologia , Channelrhodopsins , Neurônios GABAérgicos/metabolismo , Camundongos
10.
Neuron ; 77(1): 155-67, 2013 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-23312523

RESUMO

Subtypes of GABAergic interneurons (INs) are crucial for cortical function, yet their specific roles are largely unknown. In contrast to supra- and infragranular layers, where most somatostatin-expressing (SOM) INs are layer 1-targeting Martinotti cells, the axons of SOM INs in layer 4 of somatosensory cortex largely remain within layer 4. Moreover, we found that whereas layers 2/3 SOM INs target mainly pyramidal cells (PCs), layer 4 SOM INs target mainly fast-spiking (FS) INs. Accordingly, optogenetic inhibition of SOM INs in an active cortical network increases the firing of layers 2/3 PCs whereas it decreases the firing of layer 4 principal neurons (PNs). This unexpected effect of SOM INs on layer 4 PNs occurs via their inhibition of local FS INs. These results reveal a disinhibitory microcircuit in the thalamorecipient layer through interactions among subtypes of INs and suggest that the SOM IN-mediated disinhibition represents an important circuit mechanism for cortical information processing.


Assuntos
Neurônios GABAérgicos/fisiologia , Interneurônios/metabolismo , Neocórtex/metabolismo , Inibição Neural/genética , Somatostatina/biossíntese , Tálamo/metabolismo , Potenciais de Ação/fisiologia , Animais , Animais Recém-Nascidos , Regulação da Expressão Gênica , Camundongos , Camundongos Transgênicos , Neocórtex/citologia , Somatostatina/genética , Tálamo/citologia
13.
Eur J Neurosci ; 26(8): 2334-48, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17953622

RESUMO

The occipital cortex, normally visual, can be activated by auditory or somatosensory tasks in the blind. This cross-modal compensation appears after early or late onset of blindness with differences in activation between early and late blind. This could support the hypothesis of a reorganization of sensory pathways in the early blind that does not occur in later onset blindness. Using immunohistochemistry of the c-Fos protein following a white noise stimulus and injections of the anterograde tracer dextran-biotin in the inferior colliculus, we studied how the occurrence of blindness influences cross-modal compensation in the mutant anophthalmic mouse strain and in C57BL/6 mice enucleated at birth. We observed, in mutant mice, immunolabeled nuclei in the visual thalamus - the dorsal lateral geniculate nucleus - in the primary visual area (V1) and a few labeled nuclei in the secondary visual area (V2). In enucleated mice, we observed auditory activity mainly in V2 but also sparsely in V1. No labeled cells could be found in the visual thalamus. Tracing studies confirmed the difference between anophthalmic and birth-enucleated mice: whereas the first group showed inferior colliculus projections entering both the dorsal lateral geniculate and the latero-posterior nuclei, in the second, auditory fibers were found only within the latero-posterior thalamic nucleus. None was found in controls with intact eyes. We suggest that the prenatal period of spontaneous retinal activity shapes the differences of the sensory reorganization in mice.


Assuntos
Anoftalmia/fisiopatologia , Percepção Auditiva/fisiologia , Cegueira/fisiopatologia , Vias Visuais/fisiopatologia , Estimulação Acústica/métodos , Análise de Variância , Animais , Animais Recém-Nascidos , Córtex Auditivo/metabolismo , Córtex Auditivo/patologia , Biotina/análogos & derivados , Biotina/metabolismo , Contagem de Células/métodos , Dextranos/metabolismo , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Proteínas Proto-Oncogênicas c-fos/metabolismo , Vias Visuais/patologia
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