Absence of interhemispheric connections of area 17 during development in the monkey

Our understanding of the development of cortical connectivity largely stems from studies of the ontogeny of interhemispheric pathways in carnivores, rodents and lagomorphs. Early in development, cortical neurons projecting to the contralateral hemisphere through the corpus callosum (callosal projection neurons) have a widespread distribution. As maturation proceeds, callosal projection neurons become restricted to those cortical regions that are connected in the adult. In newborn cats and rats, for example, callosal projection neurons are not restricted to the 17-18 border as in the adult, but are found throughout areas 17 and 18. The macaque monkey is an exception, because at birth it has an adult-like distribution of callosal projection neurons in area 18, with practically none in area 17. Here we show that whereas area 17 is devoid of interhemispheric connections throughout prenatal development, the distribution of callosal projection neurons in area 18 shows the common sequence of an early widespread distribution followed by regression. The absence of callosal projection neurons in area 17 throughout ontogeny may well be a feature unique to Old World primates.     

Cortical representations of olfactory input by trans-synaptic tracing

In the mouse, each class of olfactory receptor neurons expressing a given odorant receptor has convergent axonal projections to two specific glomeruli in the olfactory bulb, thereby creating an odour map. However, it is unclear how this map is represented in the olfactory cortex. Here we combine rabies-virus-dependent retrograde mono-trans-synaptic labelling with genetics to control the location, number and type of 'starter' cortical neurons, from which we trace their presynaptic neurons. We find that individual cortical neurons receive input from multiple mitral cells representing broadly distributed glomeruli. Different cortical areas represent the olfactory bulb input differently. For example, the cortical amygdala preferentially receives dorsal olfactory bulb input, whereas the piriform cortex samples the whole olfactory bulb without obvious bias. These differences probably reflect different functions of these cortical areas in mediating innate odour preference or associative memory. The trans-synaptic labelling method described here should be widely applicable to mapping connections throughout the mouse nervous system.     

Specificity of cortico-cortical connections in monkey visual system

When the primate primary visual cortex, area 17, is stained for the mitochondrial enzyme cytochrome oxidase, it shows a striking polka-dot pattern (cytochrome oxidase blobs). Area 18, the second visual area, shows a cytochrome-oxidase pattern of coarse alternating thick and thin stripes running perpendicular to the 17-18 border and separated by lighter (interstripe) regions. Here we show that the thin cytochrome oxidase stripes, and possibly also the thick stripes, in area 18 receive projections specifically from the blobs in area 17, and that the interstripe regions of 18 receive projections from the interblob matrix of area 17. This indicates a specificity of cortico-cortical connections far exceeding the demands of topographical mapping. Together with our physiological results, it suggests that within the pathway from area 17 to area 18 different kinds of information may be handled separately and in parallel.     

An intrinsic mechanism of corticogenesis from embryonic stem cells

The cerebral cortex develops through the coordinated generation of dozens of neuronal subtypes, but the mechanisms involved remain unclear. Here we show that mouse embryonic stem cells, cultured without any morphogen but in the presence of a sonic hedgehog inhibitor, recapitulate in vitro the major milestones of cortical development, leading to the sequential generation of a diverse repertoire of neurons that display most salient features of genuine cortical pyramidal neurons. When grafted into the cerebral cortex, these neurons develop patterns of axonal projections corresponding to a wide range of cortical layers, but also to highly specific cortical areas, in particular visual and limbic areas, thereby demonstrating that the identity of a cortical area can be specified without any influence from the brain. The discovery of intrinsic corticogenesis sheds new light on the mechanisms of neuronal specification, and opens new avenues for the modelling and treatment of brain diseases.     

Peripheral organs control central neurogenesis in the leech

Interactions between developing nerve centres and peripheral targets are known to affect neuronal survival and thus regulate the adult number of neurons in many systems. Here we provide evidence that peripheral tissues can also influence cell numbers by stimulating the production of neurons. In the leech Hirudo medicinalis, there is a population of several hundred neurons that is found only in the two segmental ganglia that innervate the genitalia and which seem to be added gradually during post-embryonic maturation. By monitoring 5-bromo-2'-deoxyuridine incorporation immunohistochemically, we have now determined that these neurons are actually born late in embryogenesis, well after all other central neurons are born and after efferent and afferent projections are established between these ganglia and the periphery. Ablation of the male genitalia early in embryogenesis, or evulsion of the nerves that connect them to the ganglia, prevent the birth of these neurons. However, they fail to appear ectopically when male genitalia are transplanted to other segments, despite innervation by local ganglia. We conclude that the generation of the late-appearing neurons depends on a highly localized signal produced by the male genitalia, to which only the ganglia that normally innervate these organs have the capacity to respond.     

Gain control by layer six in cortical circuits of vision

After entering the cerebral cortex, sensory information spreads through six different horizontal neuronal layers that are interconnected by vertical axonal projections. It is believed that through these projections layers can influence each other's response to sensory stimuli, but the specific role that each layer has in cortical processing is still poorly understood. Here we show that layer six in the primary visual cortex of the mouse has a crucial role in controlling the gain of visually evoked activity in neurons of the upper layers without changing their tuning to orientation. This gain modulation results from the coordinated action of layer six intracortical projections to superficial layers and deep projections to the thalamus, with a substantial role of the intracortical circuit. This study establishes layer six as a major mediator of cortical gain modulation and suggests that it could be a node through which convergent inputs from several brain areas can regulate the earliest steps of cortical visual processing.     

动物行为中不同脑区神经元活动的比较

在12头家兔操作式摄食行为中,记录不同脑区（皮质视区、运动区、海马背区）172个神经元的单位放电,发现每个脑区都有神经元的变化与行为的不同方面（环境、运动、目的）相关。又发现：与行为某一方面相关变化的神经元数量在不同脑区是不等的,最显著的差异见于皮质视区与运动区：在皮质视区,大部分不是“环境”神经元,而是“运动” 神经元;在皮质运动区,大部分不是“运动”神经元,而是“目的”神经元。这可能与此二区的组织结构的明显差异有关。     

Temporal identity in axonal target layer recognition

The segregation of axon and dendrite projections into distinct synaptic layers is a fundamental principle of nervous system organization and the structural basis for information processing in the brain. Layer-specific recognition molecules that allow projecting neurons to stabilize transient contacts and initiate synaptogenesis have been identified. However, most of the neuronal cell-surface molecules critical for layer organization are expressed broadly in the developing nervous system, raising the question of how these so-called permissive adhesion molecules support synaptic specificity. Here we show that the temporal expression dynamics of the zinc-finger protein sequoia is the major determinant of Drosophila photoreceptor connectivity into distinct synaptic layers. Neighbouring R8 and R7 photoreceptors show consecutive peaks of elevated sequoia expression, which correspond to their sequential target-layer innervation. Loss of sequoia in R7 leads to a projection switch into the R8 recipient layer, whereas a prolonged expression in R8 induces a redirection of their axons into the R7 layer. The sequoia-induced axon targeting is mediated through the ubiquitously expressed Cadherin-N cell adhesion molecule. Our data support a model in which recognition specificity during synaptic layer formation is generated through a temporally restricted axonal competence to respond to broadly expressed adhesion molecules. Because developing neurons innervating the same target area often project in a distinct, birth-order-dependent sequence, temporal identity seems to contain crucial information in generating not only cell type diversity during neuronal division but also connection diversity of projecting neurons.     

Odorant receptors instruct functional circuitry in the mouse olfactory bulb

The mammalian olfactory system detects and discriminates thousands of odorants using many different receptors expressed by sensory neurons in the nasal epithelium. Axonal projections from these neurons to the main olfactory bulbs form reproducible patterns of glomeruli in two widely separated regions of each bulb, creating two mirror-symmetric maps of odorant receptor projections. To investigate whether odorant receptors organize neural circuitry in the olfactory bulb, we have examined a genetically modified mouse line, rI7 --> M71, in which a functionally characterized receptor, rI7, has been substituted into the M71 receptor locus. Here we show that despite their ectopic location the resulting glomeruli are responsive to known ligands of the rI7 receptor, attract postsynaptic innervation by mitral/tufted cell dendrites, and endow these cells with responses that are characteristic of the rI7 receptor. External tufted cells receiving input from rI7 --> M71 glomeruli form precise intrabulbar projections that link medial and lateral rI7 --> M71 glomeruli anatomically, thus providing a substrate for coordinating isofunctional glomeruli. We conclude that odorant receptor identity in epithelial neurons determines not only glomerular convergence and function, but also functional circuitry in the olfactory bulb.     

中央上核向大脑皮质的纤维投射——HRP逆行标记法研究

本文用辣根过氧化物的酶(HRP)逆行标记法对中央上核(CS)向大脑皮质的纤维投射进行了研究。观察结果表明;CS向大脑皮质投射的范围很广泛,除压上回和视区以外的大部分大脑皮质都接受CS的投射纤维,但从整体上看前半皮质多于后半皮质。在各脑区的注射例中,海马的标记细胞最多,其次是隔区,前乙状回,后乙状回和扣带回。标记细胞为中等大小的卵圆形细胞,位于核的中央部。     

面神经核神经纤维联系及功能

面神经核作为一个传统意义上的运动性神经核团,在咀嚼、吞咽、吸吮、表情和发音等方面发挥重要作用.近年来的研究表明,面神经核内除了有运动性神经元外,还有形态较小的非运动性神经元,它们可能参与机体呼吸等其他功能活动的调节.本文主要介绍面神经核的形态结构,纤维联系及功能,以便更深入、全面的认识面神经核.     

中缝背核向大脑皮质的定位投射

目的 :研究RD向大脑皮质投射的范围、起源细胞的形态及其在核内的局部定位关系 .方法 :采用HRP逆轴突传递法对 2 5只猫RD向大脑皮质的投射进行了全面的观察 .结果 :①RD向除压上回和视区以外的大部分大脑皮质有着数量不等的纤维投射 ,但主要集中于前半皮质 ,其中向前乙状回的投射最为密集 .②起源细胞主要分布于RD的背侧部和腹侧部 ,背侧部以多极细胞为主 ,腹侧部多为梭形细胞 .③RD向压旁回 ,海马和膈区投射的起源细胞位于核的中、下段 ,而向其他皮质投射的起源细胞主要集中于核的中、上段 .结论 :RD向大脑皮质有着广泛的投射 ,这些投射的起源细胞在RD内具有明显的局部定位     

1980—2015 年清水河流域水系连通变化研究

为揭示城市化发展情景下区域水系连通的变化规律, 以永定河支流清水河流域为对象, 集成遥感影像、统计资料及土地利用等数据, 运用河流连通性综合评价体系, 将基于障碍物累积影响的河流纵向连通性及基于土地破碎度的河流横向连通性相结合, 系统性地研究1980—2015年清水河流域的水系连通性变化。根据专家知识并结合清水河实际情况, 可将清水河河道阻碍物分为水库、水闸、漫水桥和河道堆积物4种类型。1980—2015年阻碍物的数量持续增长, 2000年比1980年增加10.4%, 2015年增加23.9%。1980—2015年,清水河流域纵向连通性整体上呈升高趋势, 纵向连通性差的汇水区比例由1980年的40%逐渐降低 2015年的14%。纵向连通性升高的区域集中在流域东部及中部, 西南部部分汇水区连通性加剧恶化。河流横向连通性整体上变化不明显, 其中流域西部有所下降, 东部有所好转。1980—2015年清水河流域综合连通性整体上呈升高趋势, 综合连通性差的汇水区占比在1980, 2000和 2015年分别为26%, 17%和11%。综合连通性升高的区域集中在流域东部, 而流域西南部部分区域连通性始终较差。研究结果揭示了京津冀城市化进程中流域连通性的变化规律, 可为区域防洪减灾和河流生态修复提供参考。     

Bold claims for optogenetics

In a recent Letter to Nature, Lee and colleagues combined optogenetic stimulation with functional magnetic resonance imaging (ofMRI) to examine the relationship between pyramidal-cell spiking and the blood oxygenation level dependent (BOLD) signal. To do so, they injected an adeno-associated viral vector into the primary motor cortex (M1) of adult rats to drive the expression of channelrhodopsin (ChR2) in cortical projection neurons, thus making them sensitive to light. The authors then used combined light stimulation and functional magnetic resonance imaging (fMRI) to examine the effects of selective activation of the light-sensitive pyramidal cells on the BOLD signal, as well as to probe the value of this methodology for mapping brain connectivity. They found that excitation of these neurons induced positive BOLD signals both in the injected M1 region and in remote target thalamic nuclei receiving direct projections from that region, and concluded that ofMRI reliably links positive BOLD signals with increased local neuronal excitation. However, their analysis neglects the almost immediate activation of other circuits that could lead to the generation of BOLD signals through local perisynaptic rather than spiking activity. Their experiments therefore do not pin down the identity of the specific neuronal signals that give rise to the BOLD signal.     

Correlated binocular activity guides recovery from monocular deprivation

Monocular deprivation (MD) has much more rapid and severe effects on the ocular dominance of neurons in the primary visual cortex (V1) than does binocular deprivation. This finding underlies the widely held hypothesis that the developmental plasticity of ocular dominance reflects competitive interactions for synaptic space between inputs from the two eyes. According to this view, the relative levels of evoked activity in afferents representing the two eyes determine functional changes in response to altered visual experience. However, if the deprived eye of a monocularly deprived kitten is simply reopened, there is substantial physiological and behavioural recovery, leading to the suggestion that absolute activity levels, or some other non-competitive mechanisms, determine the degree of recovery from MD. Here we provide evidence that correlated binocular input is essential for such recovery. Recovery is far less complete if the two eyes are misaligned after a period of MD. This is a powerful demonstration of the importance of cooperative, associative mechanisms in the developing visual cortex.     

Spatially asymmetric reorganization of inhibition establishes a motion-sensitive circuit

Spatial asymmetries in neural connectivity have an important role in creating basic building blocks of neuronal processing. A key circuit module of directionally selective (DS) retinal ganglion cells is a spatially asymmetric inhibitory input from starburst amacrine cells. It is not known how and when this circuit asymmetry is established during development. Here we photostimulate mouse starburst cells targeted with channelrhodopsin-2 (refs 6-8) while recording from a single genetically labelled type of DS cell. We follow the spatial distribution of synaptic strengths between starburst and DS cells during early postnatal development before these neurons can respond to a physiological light stimulus, and confirm connectivity by monosynaptically restricted trans-synaptic rabies viral tracing. We show that asymmetry develops rapidly over a 2-day period through an intermediate state in which random or symmetric synaptic connections have been established. The development of asymmetry involves the spatially selective reorganization of inhibitory synaptic inputs. Intriguingly, the spatial distribution of excitatory synaptic inputs from starburst cells is significantly more symmetric than that of the inhibitory inputs at the end of this developmental period. Our work demonstrates a rapid developmental switch from a symmetric to asymmetric input distribution for inhibition in the neural circuit of a principal cell.     

Functional connectivity in the retina at the resolution of photoreceptors

To understand a neural circuit requires knowledge of its connectivity. Here we report measurements of functional connectivity between the input and ouput layers of the macaque retina at single-cell resolution and the implications of these for colour vision. Multi-electrode technology was used to record simultaneously from complete populations of the retinal ganglion cell types (midget, parasol and small bistratified) that transmit high-resolution visual signals to the brain. Fine-grained visual stimulation was used to identify the location, type and strength of the functional input of each cone photoreceptor to each ganglion cell. The populations of ON and OFF midget and parasol cells each sampled the complete population of long- and middle-wavelength-sensitive cones. However, only OFF midget cells frequently received strong input from short-wavelength-sensitive cones. ON and OFF midget cells showed a small non-random tendency to selectively sample from either long- or middle-wavelength-sensitive cones to a degree not explained by clumping in the cone mosaic. These measurements reveal computations in a neural circuit at the elementary resolution of individual neurons.     

Retinotopic order appears before ocular separation in developing visual pathways

In mammals, the major subcortical visual structures receive projections from both eyes, with the uncrossed projection being smaller than the crossed. Each projection is arranged as a separate orderly map of one hemiretina. Although these hemiretinal maps are separate in the nuclei, they are aligned so that the representations of points in the visual field are in register, thus there is a continuity of visual field representation between them. During the early development of the binocular pathways, terminals from the two eyes overlap almost entirely. As development proceeds, terminals arising from each eye segregate to form the adult pattern. In the present study, local retinal lesions were made in ferrets at various stages in development before the separation of the projections from the two eyes. A neuronal tracer was then injected into the damaged eye, defining the pattern of projection from that eye. As reported here, the lesion resulted in a limited interruption in the pattern of terminal label on both sides of the brain, demonstrating that terminals from each eye are arranged in an orderly retinotopic manner at this stage. hence, during later development, as one projection is reduced relative to the other, the two maps must slide in relation to each other.     

Functional specificity of local synaptic connections in neocortical networks

Neuronal connectivity is fundamental to information processing in the brain. Therefore, understanding the mechanisms of sensory processing requires uncovering how connection patterns between neurons relate to their function. On a coarse scale, long-range projections can preferentially link cortical regions with similar responses to sensory stimuli. But on the local scale, where dendrites and axons overlap substantially, the functional specificity of connections remains unknown. Here we determine synaptic connectivity between nearby layer 2/3 pyramidal neurons in vitro, the response properties of which were first characterized in mouse visual cortex in vivo. We found that connection probability was related to the similarity of visually driven neuronal activity. Neurons with the same preference for oriented stimuli connected at twice the rate of neurons with orthogonal orientation preferences. Neurons responding similarly to naturalistic stimuli formed connections at much higher rates than those with uncorrelated responses. Bidirectional synaptic connections were found more frequently between neuronal pairs with strongly correlated visual responses. Our results reveal the degree of functional specificity of local synaptic connections in the visual cortex, and point to the existence of fine-scale subnetworks dedicated to processing related sensory information.     

Analgesia and hyperalgesia from GABA-mediated modulation of the cerebral cortex

It is known that pain perception can be altered by mood, attention and cognition, or by direct stimulation of the cerebral cortex, but we know little of the neural mechanisms underlying the cortical modulation of pain. One of the few cortical areas consistently activated by painful stimuli is the rostral agranular insular cortex (RAIC) where, as in other parts of the cortex, the neurotransmitter gamma-aminobutyric acid (GABA) robustly inhibits neuronal activity. Here we show that changes in GABA neurotransmission in the RAIC can raise or lower the pain threshold--producing analgesia or hyperalgesia, respectively--in freely moving rats. Locally increasing GABA, by using an enzyme inhibitor or gene transfer mediated by a viral vector, produces lasting analgesia by enhancing the descending inhibition of spinal nociceptive neurons. Selectively activating GABA(B)-receptor-bearing RAIC neurons produces hyperalgesia through projections to the amygdala, an area involved in pain and fear. Whereas most studies focus on the role of the cerebral cortex as the end point of nociceptive processing, we suggest that cerebral cortex activity can change the set-point of pain threshold in a top-down manner.