RESUMO
Radial cell columns are a hallmark feature of cortical architecture in many mammalian species. It has long been held, based on the lack of orientation columns, that such functional units are absent in rodent primary visual cortex (V1). These observations led to the view that rodent visual cortex has a fundamentally different network architecture than that of carnivores and primates. While columns may be lacking in rodent V1, we describe in this review that modular clusters of inputs to layer 1 and projection neurons in the layers below are prominent features of the mouse visual cortex. We propose that modules organize thalamocortical inputs, intracortical processing streams, and transthalamic communications that underlie distinct sensory and sensorimotor functions.
Assuntos
Córtex Visual , Camundongos , Animais , Retroalimentação , Córtex Visual/fisiologia , Interneurônios , Sensação , Vias Visuais/fisiologia , MamíferosRESUMO
The postrhinal area (POR) is a known center for integrating spatial with nonspatial visual information and a possible hub for influencing landmark navigation by affective input from the amygdala. This may involve specific circuits within muscarinic acetylcholine receptor 2 (M2)-positive (M2+) or M2- modules of POR that associate inputs from the thalamus, cortex, and amygdala, and send outputs to the entorhinal cortex. Using anterograde and retrograde labeling with conventional and viral tracers in male and female mice, we found that all higher visual areas of the ventral cortical stream project to the amygdala, while such inputs are absent from primary visual cortex and dorsal stream areas. Unexpectedly for the presumed salt-and-pepper organization of mouse extrastriate cortex, tracing results show that inputs from the dorsal lateral geniculate nucleus and lateral posterior nucleus were spatially clustered in layer 1 (L1) and overlapped with M2+ patches of POR. In contrast, input from the amygdala to L1 of POR terminated in M2- interpatches. Importantly, the amygdalocortical input to M2- interpatches in L1 overlapped preferentially with spatially clustered apical dendrites of POR neurons projecting to amygdala and entorhinal area lateral, medial (ENTm). The results suggest that subnetworks in POR, used to build spatial maps for navigation, do not receive direct thalamocortical M2+ patch-targeting inputs. Instead, they involve local networks of M2- interpatches, which are influenced by affective information from the amygdala and project to ENTm, whose cells respond to visual landmark cues for navigation.SIGNIFICANCE STATEMENT A central purpose of visual object recognition is identifying the salience of objects and approaching or avoiding them. However, it is not currently known how the visual cortex integrates the multiple streams of information, including affective and navigational cues, which are required to accomplish this task. We find that in a higher visual area, the postrhinal cortex, the cortical sheet is divided into interdigitating modules receiving distinct inputs from visual and emotion-related sources. One of these modules is preferentially connected with the amygdala and provides outputs to entorhinal cortex, constituting a processing stream that may assign emotional salience to objects and landmarks for the guidance of goal-directed navigation.
Assuntos
Tonsila do Cerebelo/fisiologia , Córtex Entorrinal/fisiologia , Vias Neurais/fisiologia , Navegação Espacial/fisiologia , Córtex Visual/fisiologia , Animais , Córtex Entorrinal/citologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vias Neurais/citologia , Córtex Visual/citologiaRESUMO
Mammals show a wide range of brain sizes, reflecting adaptation to diverse habitats. Comparing interareal cortical networks across brains of different sizes and mammalian orders provides robust information on evolutionarily preserved features and species-specific processing modalities. However, these networks are spatially embedded, directed, and weighted, making comparisons challenging. Using tract tracing data from macaque and mouse, we show the existence of a general organizational principle based on an exponential distance rule (EDR) and cortical geometry, enabling network comparisons within the same model framework. These comparisons reveal the existence of network invariants between mouse and macaque, exemplified in graph motif profiles and connection similarity indices, but also significant differences, such as fractionally smaller and much weaker long-distance connections in the macaque than in mouse. The latter lends credence to the prediction that long-distance cortico-cortical connections could be very weak in the much-expanded human cortex, implying an increased susceptibility to disconnection syndromes such as Alzheimer disease and schizophrenia. Finally, our data from tracer experiments involving only gray matter connections in the primary visual areas of both species show that an EDR holds at local scales as well (within 1.5 mm), supporting the hypothesis that it is a universally valid property across all scales and, possibly, across the mammalian class.
Assuntos
Córtex Cerebral/fisiologia , Conectoma/métodos , Modelos Neurológicos , Rede Nervosa/fisiologia , Vias Neurais/fisiologia , Algoritmos , Animais , Córtex Cerebral/anatomia & histologia , Simulação por Computador , Feminino , Humanos , Macaca , Masculino , Camundongos , Modelos Anatômicos , Rede Nervosa/anatomia & histologia , Vias Neurais/anatomia & histologia , Especificidade da EspécieRESUMO
A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria. Using Bayesian analysis and clustering algorithms on the resulting data, we investigated the suitability of several anatomical terms and neuron names for cortical GABAergic interneurons. Moreover, we show that supervised classification models could automatically categorize interneurons in agreement with experts' assignments. These results demonstrate a practical and objective approach to the naming, characterization and classification of neurons based on community consensus.
Assuntos
Algoritmos , Córtex Cerebral/citologia , Interneurônios/classificação , Interneurônios/citologia , Terminologia como Assunto , Ácido gama-Aminobutírico/metabolismo , Animais , Teorema de Bayes , Córtex Cerebral/metabolismo , Análise por Conglomerados , Humanos , Interneurônios/metabolismoRESUMO
Previous studies of intracortical connections in mouse visual cortex have revealed two subnetworks that resemble the dorsal and ventral streams in primates. Although calcium imaging studies have shown that many areas of the ventral stream have high spatial acuity whereas areas of the dorsal stream are highly sensitive for transient visual stimuli, there are some functional inconsistencies that challenge a simple grouping into "what/perception" and "where/action" streams known in primates. The superior colliculus (SC) is a major center for processing of multimodal sensory information and the motor control of orienting the eyes, head, and body. Visual processing is performed in superficial layers, whereas premotor activity is generated in deep layers of the SC. Because the SC is known to receive input from visual cortex, we asked whether the projections from 10 visual areas of the dorsal and ventral streams terminate in differential depth profiles within the SC. We found that inputs from primary visual cortex are by far the strongest. Projections from the ventral stream were substantially weaker, whereas the sparsest input originated from areas of the dorsal stream. Importantly, we found that ventral stream inputs terminated in superficial layers, whereas dorsal stream inputs tended to be patchy and either projected equally to superficial and deep layers or strongly preferred deep layers. The results suggest that the anatomically defined ventral and dorsal streams contain areas that belong to distinct functional systems, specialized for the processing of visual information and visually guided action, respectively.
Assuntos
Colículos Superiores/citologia , Colículos Superiores/fisiologia , Córtex Visual/citologia , Córtex Visual/fisiologia , Vias Visuais/citologia , Vias Visuais/fisiologia , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Mouse visual cortex is subdivided into multiple distinct, hierarchically organized areas that are interconnected through feedforward (FF) and feedback (FB) pathways. The principal synaptic targets of FF and FB axons that reciprocally interconnect primary visual cortex (V1) with the higher lateromedial extrastriate area (LM) are pyramidal cells (Pyr) and parvalbumin (PV)-expressing GABAergic interneurons. Recordings in slices of mouse visual cortex have shown that layer 2/3 Pyr cells receive excitatory monosynaptic FF and FB inputs, which are opposed by disynaptic inhibition. Most notably, inhibition is stronger in the FF than FB pathway, suggesting pathway-specific organization of feedforward inhibition (FFI). To explore the hypothesis that this difference is due to diverse pathway-specific strengths of the inputs to PV neurons we have performed subcellular Channelrhodopsin-2-assisted circuit mapping in slices of mouse visual cortex. Whole-cell patch-clamp recordings were obtained from retrobead-labeled FF(V1âLM)- and FB(LMâV1)-projecting Pyr cells, as well as from tdTomato-expressing PV neurons. The results show that the FF(V1âLM) pathway provides on average 3.7-fold stronger depolarizing input to layer 2/3 inhibitory PV neurons than to neighboring excitatory Pyr cells. In the FB(LMâV1) pathway, depolarizing inputs to layer 2/3 PV neurons and Pyr cells were balanced. Balanced inputs were also found in the FF(V1âLM) pathway to layer 5 PV neurons and Pyr cells, whereas FB(LMâV1) inputs to layer 5 were biased toward Pyr cells. The findings indicate that FFI in FF(V1âLM) and FB(LMâV1) circuits are organized in a pathway- and lamina-specific fashion.
Assuntos
Retroalimentação Fisiológica/fisiologia , Rede Nervosa/fisiologia , Inibição Neural/fisiologia , Córtex Visual/fisiologia , Vias Visuais/fisiologia , Animais , Potenciais Pós-Sinápticos Excitadores/fisiologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Vias Neurais/fisiologia , Técnicas de Cultura de Órgãos , Estimulação Luminosa/métodosRESUMO
Interactions between feedback connections from higher cortical areas and local horizontal connections within primary visual cortex (V1) were shown to play a role in contextual processing in different behavioral states. Layer 1 (L1) is an important part of the underlying network. This cell-sparse layer is a target of feedback and local inputs, and nexus for contacts onto apical dendrites of projection neurons in the layers below. Importantly, L1 is a site for coupling inputs from the outside world with internal information. To determine whether all of these circuit elements overlap in L1, we labeled the horizontal network within mouse V1 with anterograde and retrograde viral tracers. We found two types of local horizontal connections: short ones that were tangentially limited to the representation of the point image, and long ones which reached beyond the receptive field center, deep into its surround. The long connections were patchy and terminated preferentially in M2 muscarinic acetylcholine receptor-negative (M2-) interpatches. Anterogradely labeled inputs overlapped in M2-interpatches with apical dendrites of retrogradely labeled L2/3 and L5 cells, forming module-selective loops between topographically distant locations. Previous work showed that L1 of M2-interpatches receive inputs from the lateral posterior thalamic nucleus (LP) and from a feedback network from areas of the medial dorsal stream, including the secondary motor cortex. Together, these findings suggest that interactions in M2-interpatches play a role in processing visual inputs produced by object-and self-motion.
RESUMO
The computation and comparison of subjective values underlying economic choices rely on the orbitofrontal cortex (OFC). In this area, distinct groups of neurons encode the value of individual options, the binary choice outcome, and the chosen value. These variables capture both the input and the output of the choice process, suggesting that the cell groups found in OFC constitute the building blocks of a decision circuit. Here we show that this neural circuit is longitudinally stable. Using two-photon calcium imaging, we recorded from mice choosing between different juice flavors. Recordings of individual cells continued for up to 20 weeks. For each cell and each pair of sessions, we compared the activity profiles using cosine similarity, and we assessed whether the cell encoded the same variable in both sessions. These analyses revealed a high degree of stability and a modest representational drift. A quantitative estimate indicated this drift would not randomize the circuit within the animal's lifetime.
RESUMO
Much of the information used for visual perception and visually guided actions is processed in complex networks of connections within the cortex. To understand how this works in the normal brain and to determine the impact of disease, mice are promising models. In primate visual cortex, information is processed in a dorsal stream specialized for visuospatial processing and guided action and a ventral stream for object recognition. Here, we traced the outputs of 10 visual areas and used quantitative graph analytic tools of modern network science to determine, from the projection strengths in 39 cortical targets, the community structure of the network. We found a high density of the cortical graph that exceeded that shown previously in monkey. Each source area showed a unique distribution of projection weights across its targets (i.e., connectivity profile) that was well fit by a lognormal function. Importantly, the community structure was strongly dependent on the location of the source area: outputs from medial/anterior extrastriate areas were more strongly linked to parietal, motor, and limbic cortices, whereas lateral extrastriate areas were preferentially connected to temporal and parahippocampal cortices. These two subnetworks resemble dorsal and ventral cortical streams in primates, demonstrating that the basic layout of cortical networks is conserved across species.
Assuntos
Mapeamento Encefálico/estatística & dados numéricos , Córtex Cerebral/anatomia & histologia , Córtex Visual/anatomia & histologia , Animais , Mapeamento Encefálico/métodos , Feminino , Iontoforese/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Estatísticos , Vias Neurais/anatomia & histologia , Técnicas de Rastreamento Neuroanatômico/métodos , Técnicas de Rastreamento Neuroanatômico/estatística & dados numéricos , Marcadores do Trato Nervoso/administração & dosagemRESUMO
Neuroscience produces a vast amount of data from an enormous diversity of neurons. A neuronal classification system is essential to organize such data and the knowledge that is derived from them. Classification depends on the unequivocal identification of the features that distinguish one type of neuron from another. The problems inherent in this are particularly acute when studying cortical interneurons. To tackle this, we convened a representative group of researchers to agree on a set of terms to describe the anatomical, physiological and molecular features of GABAergic interneurons of the cerebral cortex. The resulting terminology might provide a stepping stone towards a future classification of these complex and heterogeneous cells. Consistent adoption will be important for the success of such an initiative, and we also encourage the active involvement of the broader scientific community in the dynamic evolution of this project.
Assuntos
Córtex Cerebral/citologia , Interneurônios , Ácido gama-Aminobutírico/metabolismo , Potenciais de Ação , Axônios/ultraestrutura , Córtex Cerebral/metabolismo , Humanos , Interneurônios/classificação , Interneurônios/citologia , Interneurônios/metabolismo , Sinapses/ultraestruturaRESUMO
It is widely held that the spatial processing functions underlying rodent navigation are similar to those encoding human episodic memory (Doeller et al., 2010). Spatial and nonspatial information are provided by all senses including vision. It has been suggested that visual inputs are fed to the navigational network in cortex and hippocampus through dorsal and ventral intracortical streams (Whitlock et al., 2008), but this has not been shown directly in rodents. We have used cytoarchitectonic and chemoarchitectonic markers, topographic mapping of receptive fields, and pathway tracing to determine in mouse visual cortex whether the lateromedial field (LM) and the anterolateral field (AL), which are the principal targets of primary visual cortex (V1) (Wang and Burkhalter, 2007) specialized for processing nonspatial and spatial visual information (Gao et al., 2006), are distinct areas with diverse connections. We have found that the LM/AL border coincides with a change in type 2 muscarinic acetylcholine receptor expression in layer 4 and with the representation of the lower visual field periphery. Our quantitative analyses also show that LM strongly projects to temporal cortex as well as the lateral entorhinal cortex, which has weak spatial selectivity (Hargreaves et al., 2005). In contrast, AL has stronger connections with posterior parietal cortex, motor cortex, and the spatially selective medial entorhinal cortex (Haftig et al., 2005). These results support the notion that LM and AL are architecturally, topographically, and connectionally distinct areas of extrastriate visual cortex and that they are gateways for ventral and dorsal streams.
Assuntos
Vias Neurais/anatomia & histologia , Receptor Muscarínico M2/metabolismo , Córtex Visual/anatomia & histologia , Animais , Bisbenzimidazol/administração & dosagem , Córtex Entorrinal/anatomia & histologia , Feminino , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microinjeções , Córtex Motor/anatomia & histologia , Lobo Parietal/anatomia & histologia , Lobo Temporal/anatomia & histologiaRESUMO
Rapidly activating and rapidly inactivating voltage-gated A-type K+ currents, IA, are key determinants of neuronal excitability and several studies suggest a critical role for the Kv4.2 pore-forming α subunit in the generation of IA channels in hippocampal and cortical pyramidal neurons. The experiments here demonstrate that Kv4.2, Kv4.3 and Kv1.4 all contribute to the generation of IA channels in mature cortical pyramidal (CP) neurons and that Kv4.2-, Kv4.3- and Kv1.4-encoded IA channels play distinct roles in regulating the intrinsic excitability and the firing properties of mature CP neurons. In vivo loss of Kv4.2, for example, alters the input resistances, current thresholds for action potential generation and action potential repolarization of mature CP neurons. Elimination of Kv4.3 also prolongs action potential duration, whereas the input resistances and the current thresholds for action potential generation in Kv4.3−/− and WT CP neurons are indistinguishable. In addition, although increased repetitive firing was observed in both Kv4.2−/− and Kv4.3−/− CP neurons, the increases in Kv4.2−/− CP neurons were observed in response to small, but not large, amplitude depolarizing current injections, whereas firing rates were higher in Kv4.3−/− CP neurons only with large amplitude current injections. In vivo loss of Kv1.4, in contrast, had minimal effects on the intrinsic excitability and the firing properties of mature CP neurons. Comparison of the effects of pharmacological blockade of Kv4-encoded currents in Kv1.4−/− and WT CP neurons, however, revealed that Kv1.4-encoded IA channels do contribute to controlling resting membrane potentials, the regulation of current thresholds for action potential generation and repetitive firing rates in mature CP neurons.
Assuntos
Canal de Potássio Kv1.4/metabolismo , Potenciais da Membrana/fisiologia , Neurônios/fisiologia , Tratos Piramidais/fisiologia , Canais de Potássio Shal/metabolismo , Animais , Regulação da Expressão Gênica/fisiologia , Canal de Potássio Kv1.4/genética , Potenciais da Membrana/efeitos dos fármacos , Camundongos , Neurônios/citologia , Canais de Potássio Shal/genéticaRESUMO
Neocortical computations underlying vision are performed by a distributed network of functionally specialized areas. Mouse visual cortex, a dense interareal network that exhibits hierarchical properties, comprises subnetworks interconnecting distinct processing streams. To determine the layout of the mouse visual hierarchy, we have evaluated the laminar patterns formed by interareal axonal projections originating in each of ten areas. Reciprocally connected pairs of areas exhibit feedforward/feedback relationships consistent with a hierarchical organization. Beta regression analyses, which estimate a continuous hierarchical distance measure, indicate that the network comprises multiple nonhierarchical circuits embedded in a hierarchical organization of overlapping levels. Single-unit recordings in anaesthetized mice show that receptive field sizes are generally consistent with the hierarchy, with the ventral stream exhibiting a stricter hierarchy than the dorsal stream. Together, the results provide an anatomical metric for hierarchical distance, and reveal both hierarchical and nonhierarchical motifs in mouse visual cortex.
Assuntos
Córtex Visual/fisiologia , Vias Visuais/fisiologia , Animais , Biologia Computacional , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Córtex Visual/patologia , Vias Visuais/patologiaRESUMO
It is generally accepted that in mammals visual information is sent to the brain along functionally specialized parallel pathways, but whether the mouse visual system uses similar processing strategies is not known. It is important to resolve this issue because the mouse brain provides a tractable system for developing a cellular and molecular understanding of disorders affecting spatiotemporal visual processing. We have used single-unit recordings in mouse primary visual cortex to study whether individual neurons are more sensitive to one set of sensory cues than another. Our quantitative analyses show that neurons with short response latencies have low spatial acuity and high sensitivity to contrast, temporal frequency, and speed, whereas neurons with long latencies have high spatial acuity, low sensitivities to contrast, temporal frequency, and speed. These correlations suggest that neurons in mouse V1 receive inputs from a weighted combination of parallel afferent pathways with distinct spatiotemporal sensitivities.
Assuntos
Neurônios/fisiologia , Córtex Visual/fisiologia , Percepção Visual/fisiologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Microeletrodos , Percepção de Movimento/fisiologia , Estimulação Luminosa , Fatores de Tempo , Vias Visuais/fisiologiaRESUMO
Latent nystagmus (LN) is the by-product of fusion maldevelopment in infancy. Because fusion maldevelopment--in the form of strabismus and amblyopia--is common, LN is a prevalent form of pathologic nystagmus encountered in clinical practice. It originates as an afferent visual pathway disorder. To unravel the mechanism for LN, we studied patients and nonhuman primates with maldeveloped fusion. These experiments have revealed that loss of binocular connections within striate cortex (area V1) in the first months of life is the necessary and sufficient cause of LN. The severity of LN increases systematically with longer durations of binocular decorrelation and greater losses of V1 connections. Decorrelation durations that exceed the equivalent of 2-3 months in human development result in an LN prevalence of 100%. No manipulation of brain stem motor pathways is required. The binocular maldevelopment originating in area V1 is passed on to downstream extrastriate regions of cerebral cortex that drive conjugate gaze, notably MSTd. Conjugate gaze is stable when MSTd neurons of the right and left cerebral hemispheres have balanced binocular activity. Fusion maldevelopment in infancy causes unbalanced monocular activity. If input from one eye dominates and the other is suppressed, MSTd in one hemisphere becomes more active. Acting through downstream projections to the ipsilateral nucleus of the optic tract, the eyes are driven conjugately to that side. The unbalanced MSTd drive is evident as the nasalward gaze-holding bias of LN when viewing with either eye.
Assuntos
Nistagmo Patológico/patologia , Estrabismo/patologia , Córtex Visual/fisiopatologia , Vias Visuais/fisiopatologia , Animais , Humanos , Estrabismo/fisiopatologia , Córtex Visual/crescimento & desenvolvimento , Córtex Visual/patologia , Vias Visuais/crescimento & desenvolvimento , Vias Visuais/patologiaRESUMO
Whether mouse visual cortex contains orderly feature maps is debated. The overlapping pattern of geniculocortical inputs with M2 muscarinic acetylcholine receptor-rich patches in layer 1 (L1) suggests a non-random architecture. Here, we found that L1 inputs from the lateral posterior thalamus (LP) avoid patches and target interpatches. Channelrhodopsin-2-assisted mapping of excitatory postsynaptic currents (EPSCs) in L2/3 shows that the relative excitation of parvalbumin-expressing interneurons (PVs) and pyramidal neurons (PNs) by dLGN, LP, and cortical feedback is distinct and depends on whether the neurons reside in clusters aligned with patches or interpatches. Paired recordings from PVs and PNs show that unitary inhibitory postsynaptic currents (uIPSCs) are larger in interpatches than in patches. The spatial clustering of inhibition is matched by dense clustering of PV terminals in interpatches. The results show that the excitation/inhibition balance across V1 is organized into patch and interpatch subnetworks, which receive distinct long-range inputs and are specialized for the processing of distinct spatiotemporal features.
Assuntos
Corpos Geniculados/fisiologia , Interneurônios/fisiologia , Inibição Neural/fisiologia , Células Piramidais/fisiologia , Córtex Visual/fisiologia , Animais , Mapeamento Encefálico , Potenciais Pós-Sinápticos Excitadores , Potenciais Pós-Sinápticos Inibidores , Interneurônios/metabolismo , Núcleos Laterais do Tálamo/fisiologia , Camundongos , Vias Neurais , Parvalbuminas/metabolismoRESUMO
Considerable experimental evidence has accumulated demonstrating a role for voltage-gated K(+) (Kv) channel pore-forming (alpha) subunits of the Kv4 subfamily in the generation of fast transient outward K(+), I(A), channels. Immunohistochemical data suggest that I(A) channels in hippocampal and cortical pyramidal neurons reflect the expression of homomeric Kv4.2 channels. The experiments here were designed to define directly the role of Kv4.2 in the generation of I(A) in cortical pyramidal neurons and to determine the functional consequences of the targeted deletion of Kv4.2 on the resting and active membrane properties of these cells. Whole-cell voltage-clamp recordings, obtained from visual cortical pyramidal neurons isolated from mice in which the KCND2 (Kv4.2) locus was disrupted (Kv4.2-/- mice), revealed that I(A) is indeed eliminated. In addition, the densities of other Kv current components, specifically I(K) and I(ss), are increased significantly (P < 0.001) in most ( approximately 80%) Kv4.2-/- cells. The deletion of KCND2 (Kv4.2) and the elimination of I(A) is also accompanied by the loss of the Kv4 channel accessory protein KChIP3, suggesting that in the absence of Kv4.2, the KChIP3 protein is targeted for degradation. The expression levels of several Kv alpha subunits (Kv4.3, Kv1.4, Kv2.1, Kv2.2), however, are not measurably altered in Kv4.2-/- cortices. Although I(A) is eliminated in Kv4.2-/- pyramidal neurons, the mean +/- s.e.m. current threshold for action potential generation and the waveforms of action potentials are indistinguishable from those recorded from wild-type cells. Repetitive firing is also maintained in Kv4.2-/- cortical pyramidal neurons, suggesting that the increased densities of I(K) and I(ss) compensate for the in vivo loss of I(A).
Assuntos
Potenciais de Ação/fisiologia , Relógios Biológicos/fisiologia , Ativação do Canal Iônico/fisiologia , Proteínas Interatuantes com Canais de Kv/metabolismo , Células Piramidais/fisiologia , Canais de Potássio Shal/metabolismo , Adaptação Fisiológica/fisiologia , Animais , Células Cultivadas , Proteínas Interatuantes com Canais de Kv/genética , Potenciais da Membrana/fisiologia , Camundongos , Camundongos Knockout , Canais de Potássio Shal/genéticaRESUMO
The inter-areal wiring pattern of the mouse cerebral cortex was analyzed in relation to a refined parcellation of cortical areas. Twenty-seven retrograde tracer injections were made in 19 areas of a 47-area parcellation of the mouse neocortex. Flat mounts of the cortex and multiple histological markers enabled detailed counts of labeled neurons in individual areas. The observed log-normal distribution of connection weights to each cortical area spans 5 orders of magnitude and reveals a distinct connectivity profile for each area, analogous to that observed in macaques. The cortical network has a density of 97%, considerably higher than the 66% density reported in macaques. A weighted graph analysis reveals a similar global efficiency but weaker spatial clustering compared with that reported in macaques. The consistency, precision of the connectivity profile, density, and weighted graph analysis of the present data differ significantly from those obtained in earlier studies in the mouse.
Assuntos
Conectoma/métodos , Modelos Neurológicos , Neocórtex/citologia , Animais , Feminino , Macaca , Masculino , Vias Neurais/citologia , Técnicas de Rastreamento Neuroanatômico , Especificidade da EspécieRESUMO
In cortical neurons, pore-forming alpha-subunits of the Kv4 subfamily underlie the fast transient outward K+ current (I(A)). Considerable evidence has accumulated demonstrating specific roles for I(A) channels in the generation of individual action potentials and in the regulation of repetitive firing. Although I(A) channels are thought to play a role in synaptic processing, little is known about the cell type- and synapse-specific distribution of these channels in cortical circuits. Here, we used immunolabeling with specific antibodies against Kv4.2 and Kv4.3, in combination with GABA immunogold staining, to determine the cellular, subcellular, and synaptic localization of Kv4 channels in the primary visual cortex of mice, in which subsets of pyramidal cells express yellow fluorescent protein. The results show that both Kv4.2 and Kv4.3 are concentrated in layer 1, the bottom of layer 2/3, and in layers 4 and 5/6. In all layers, clusters of Kv4.2 and Kv4.3 immunoreactivity are evident in the membranes of the somata, dendrites, and spines of pyramidal cells and GABAergic interneurons. Electron microscopic analyses revealed that Kv4.2 and Kv4.3 clusters in pyramidal cells and interneurons are excluded from putative excitatory synapses, whereas postsynaptic membranes at GABAergic synapses often contain Kv4.2 and Kv4.3. The presence of Kv4 channels at GABAergic synapses would be expected to weaken inhibition during dendritic depolarization by backpropagating action potentials. The extrasynaptic localization of Kv4 channels near excitatory synapses, in contrast, should stabilize synaptic excitation during dendritic depolarization. Thus, the synapse-specific distribution of Kv4 channels functions to optimize dendritic excitation and the association between presynaptic and postsynaptic activity.
Assuntos
Expressão Gênica/fisiologia , Neurônios/metabolismo , Canais de Potássio Shal/metabolismo , Sinapses/metabolismo , Córtex Visual/citologia , Animais , Proteínas de Bactérias/genética , Imuno-Histoquímica/métodos , Proteínas Luminescentes/genética , Camundongos , Camundongos Transgênicos , Microscopia Imunoeletrônica/métodos , Neurônios/ultraestrutura , Canais de Potássio Shal/deficiência , Sinapses/ultraestrutura , Ácido gama-Aminobutírico/metabolismoRESUMO
It is controversial whether mouse extrastriate cortex has a "simple" organization in which lateral primary visual cortex (V1) is adjoined by a single area V2 or has a "complex" organization, in which lateral V1 is adjoined by multiple distinct areas, all of which share the vertical meridian with V1. Resolving this issue is important for understanding the evolution and development of cortical arealization. We have used triple pathway tracing combined with receptive field recordings to map azimuth and elevation in the same brain and have referenced these maps against callosal landmarks. We found that V1 projects to 15 cortical fields. At least nine of these contain maps with complete and orderly representations of the entire visual hemifield and therefore represent distinct areas. One of these, PM, adjoins V1 at the medial border. Five areas, P, LM, AL, RL, and A, adjoin V1 on the lateral border, but only LM shares the vertical meridian representation with V1. This suggests that LM is homologous to V2 and that the lateral extrastriate areas do not represent modules within a single area V2. Thus, mouse visual cortex is "simple" in the sense that lateral V1 is adjoined by a single V2-like area, LM, and "complex" in having a string of areas in lateral extrastriate cortex, which receive direct V1 input. The results suggest that large numbers of areas with topologically equivalent maps of the visual field emerge early in evolution and that homologous areas are inherited in different mammalian lineages.