GABAergic internereurons are crucial components of the neocortical network, and the functional characterization of the neocortex has been greatly hindered by the lack of consensus regarding the way they should be classified. Interneurons differentiate from an electrophysiological, and a morphological point of view, as well as by the expression of molecular markers, and it remains debated if the combination of these features delineates separate classes, or if it defines a phenotypical continuum. During my PhD, I proposed myself to study the diversity of neocortical interneurons, while taking all these criterions into account. Patch-clamp recordings coupled to single-cell RT-PCR have been performed in mouse, on a sample of more than 300 neocortical interneurons, and the arborization of nearly 200 of them has been reconstructed in 3 dimensions. The electrophysiological, morphological and molecular phenotypes of sampled neurons have been quantified through a set of 56 parameters. Using this sample, we first

TY - JOUR. T1 - Graded and areal expression patterns of regulatory genes and cadherins in embryonic neocortex independent of thalamocortical input. AU - Nakagawa, Yasushi. AU - Johnson, Jane E.. AU - OLeary, Dennis D M. PY - 1999/12/15. Y1 - 1999/12/15. N2 - The differentiation of areas of the mammalian neocortex has been hypothesized to be controlled by intrinsic genetic programs and extrinsic influences such as those mediated by thalamocortical afferents (TCAs). To address the interplay between these intrinsic and extrinsic mechanisms in the process of arealization, we have analyzed the requirement of TCAs in establishing or maintaining graded or areal patterns of gene expression in the developing mouse neocortex. We describe the differential expression of Lhx2, SCIP, and Emx1, representatives of three different classes of transcription factors, and the type I1 classical cadherins Cad6 Cad8, and Cad11, which are expressed in graded or areal patterns, as well as layer- specific patterns, in ...

TY - JOUR. T1 - HP1-beta is required for development of the cerebral neocortex and neuromuscular junctions. AU - Aucott, Rebecca. AU - Bullwinkel, Jörn. AU - Yu, Yang. AU - Shi, Wei. AU - Billur, Mustafa. AU - Brown, Jeremy P. AU - Menzel, Ursula. AU - Kioussis, Dimitris. AU - Wang, Guozheng. AU - Reisert, Ingrid. AU - Weimer, Jörg. AU - Pandita, Raj K. AU - Sharma, Girdhar G. AU - Pandita, Tej K. AU - Fundele, Reinald. AU - Singh, Prim B. PY - 2008/11/17. Y1 - 2008/11/17. N2 - HP1 proteins are thought to be modulators of chromatin organization in all mammals, yet their exact physiological function remains unknown. In a first attempt to elucidate the function of these proteins in vivo, we disrupted the murine Cbx1 gene, which encodes the HP1-beta isotype, and show that the Cbx1(-/-) -null mutation leads to perinatal lethality. The newborn mice succumbed to acute respiratory failure, whose likely cause is the defective development of neuromuscular junctions within the endplate of the diaphragm. ...

Neocortical GABAergic interneuron migration and thalamo-cortical axon (TCA) pathfinding follow similar trajectories and timing, suggesting they may be interdependent. The mechanisms that regulate the radial dispersion of neocortical interneurons are incompletely understood. In this new study we report that disruption of TCA innervation, or TCA-derived glutamate, affected the laminar distribution of GABAergic interneurons in mouse neocortex, resulting in abnormal accumulation in deep layers of interneurons that failed to switch from tangential to radial orientation. Expression of the KCC2 cotransporter was elevated in interneurons of denervated cortex, and KCC2 deletion restored normal interneuron lamination in the absence of TCAs. Disruption of interneuron NMDA receptors or pharmacological inhibition of calpain also led to increased KCC2 expression and defective radial dispersion of interneurons. Thus, although TCAs are not required to guide the tangential migration of GABAergic interneurons, ...

The brain is composed of glial cells and neurons where synapses form connections between neurons and other cells. Since synapses are very small, so either a light or electron microscope is required to see them. Unlike other mammals, synapses in the human brain deteriorate rapidly upon death making them difficult to study. This project constructs a simple model for the number of synapses in the human neocortex by age and sex based on the amount of neurons. This hypothetical model can also be used to study the impact of Alzheimers disease and other forms of dementia that are marked by a decreased number of synaptic connections.

Transcriptional events involved in the development of human cerebral neocortex are poorly understood. Here, we analyzed the temporal dynamics and laterality of gene expression in human and macaque monkey neocortex. We found that interareal differences exhibit a temporal hourglass pattern, dividing t …

TY - JOUR. T1 - Unsupervised classification of high-frequency oscillations in human neocortical epilepsy and control patients. AU - Blanco, Justin A.. AU - Stead, Matt. AU - Krieger, Abba. AU - Viventi, Jonathan. AU - Marsh, W. Richard. AU - Lee, Kendall H.. AU - Worrell, Gregory A.. AU - Litt, Brian. PY - 2010/11/1. Y1 - 2010/11/1. N2 - High-frequency oscillations (HFOs) have been observed in animal and human intracranial recordings during both normal and aberrant brain states. It has been proposed that the relationship between subclasses of these oscillations can be used to identify epileptic brain. Studies of HFOs in epilepsy have been hampered by selection bias arising primarily out of the need to reduce the volume of data so that clinicians can manually review it. In this study, we introduce an algorithm for detecting and classifying these signals automatically and demonstrate the tractability of analyzing a data set of unprecedented size, over 31,000 channel-hours of intracranial ...

The primary subdivisions of the forebrain, including the neocortex and the basal ganglia, have distinct molecular and cellular properties (1,2). Previous evidence suggests that these subdivisions develop from separate proliferative zones that do not intermix (3). Here we show that cell migration occurs between the primordia of the basal ganglia and the cerebral cortex. Our results suggest that many neocortical interneurons are generated by the proliferative zone of the basal ganglia.. Neocortical neurons include two types: the excitatory pyramidal neurons and the inhibitory (GABA-containing) interneurons. During development, neocortical neurons were thought to derive from the proliferative zone of the neocortical primordium. However, studies of neuronal migration in vitro indicate that cells migrate from the lateral ganglionic eminence (LGE) (4), which is the primordium of the striatum (5), into the neocortex. Other evidence suggests that these cells might be interneurons. For example, clonally ...

The human brain owes its characteristic wrinkled appearance to its outer layer, the cerebral cortex. During human evolution, the neocortex, the evolutionarily youngest part of the cerebral cortex, expanded dramatically and had to fold into wrinkles to fit inside the restricted space of the skull. The human neocortex supports advanced cognitive skills such as reasoning and language. But how did the human neocortex become so big? The answer may lie in genes that are unique to humans, such as ARHGAP11B. Researchers at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden found that this human-specific gene, when introduced into the developing brain of ferrets, can cause an enlargement of their neocortex. ARHGAP11B causes neural progenitor cells, which are cells that produce neurons, to make more of themselves for a longer period of time. The result is an expanded neocortex. The researchers published their findings in the journal eLife. The human neocortex is roughly ...

GABA is the principal inhibitory neurotransmitter in the mature brain, but during early postnatal development the elevated [Cl(-)](i) in immature neocortical neurones causes GABA(A) receptor activation to be depolarizing. The molecular mechanisms underlying this intracellular Cl(-) accumulation rema …

Chandelier (or axo-axonic) cells are one of the most distinctive types of GABAergic interneurons in the cortex. Although they have traditionally been considered inhibitory neurons, data from rat and human neocortical preparations suggest that chandelier cells have a depolarizing effect on pyramidal neurons at resting membrane potential, and could even activate synaptic chains of neurons. At the same time, recent results from rat hippocampal chandeliers indicate a predominantly inhibitory effect on their postsynaptic targets. To better understand the function of chandelier neurons, we generated Nkx2.1Cre MADM mice, a strain of genetically engineered animals that, by expressing GFP in a subset of neocortical interneurons, enable the identification and targeting of chandelier cells in living brain slices. Using these mice, we characterized the basic electrophysiological properties of a homogeneous population of chandelier neurons from upper layers of somatosensory cortical slices. These chandelier cells

The cytoarchitectonic similarities of different neocortical regions have given rise to the idea of canonical connectivity between excitatory neurons of different layers within a column. It is unclear whether similarly general organizational principles also exist for inhibitory neocortical circuits. Here we delineate and compare local inhibitory-to-excitatory wiring patterns in all principal layers of primary motor (M1), somatosensory (S1) and visual (V1) cortex, using genetically targeted photostimulation in a mouse knock-in line that conditionally expresses channelrhodopsin-2 in GABAergic neurons. Inhibitory inputs to excitatory neurons derived largely from the same cortical layer within a three-column diameter. However, subsets of pyramidal cells in layers 2/3 and 5B received extensive translaminar inhibition. These neurons were prominent in V1, where they might correspond to complex cells, less numerous in barrel cortex and absent in M1. Although inhibitory connection patterns were stereotypical,

The human cerebral cortex is affected by a wide range of disorders and is also particularly sensitive to the effects of drugs and environmental toxins during development. Human pluripotent stem cells (hPSCs) are a unique system to model the human cerebral cortex, but replicating the complexity of this structure in terms of both neuronal diversity and developmental processes has been limited in current models. Here, Chun-Ting Lee and colleagues use hPSC aggregates without cell dissociation but with inclusion of key trophic factors to model human neocortical development. They are able to reproduce in vitro the formation of radial glia scaffolding (which supports neuronal migration), of deep and upper layers of cortical neurons, and of different neuronal subtypes (including glutamatergic and GABAergic neurons), as occurs during human neocortical development. In addition, the authors use this system to study the effects of cocaine - a drug that causes developmental toxicity in humans - and find that ...

The generation of neocortical neurons from neural progenitor cells (NPCs) is primarily controlled by transcription factors binding to DNA in the context of chromatin. To understand the complex layer of regulation that orchestrates different NPC types from the same DNA sequence, epigenome maps with cell type resolution are required. Here, we present genomewide histone methylation maps for distinct neural cell populations in the developing mouse neocortex. Using different chromatin features, we identify potential novel regulators of cortical NPCs. Moreover, we identify extensive H3K27me3 changes between NPC subtypes coinciding with major developmental and cell biological transitions. Interestingly, we detect dynamic H3K27me3 changes on promoters of several crucial transcription factors, including the basal progenitor regulator Eomes. We use catalytically inactive Cas9 fused with the histone methyltransferase Ezh2 to edit H3K27me3 at the Eomes locus in vivo, which results in reduced Tbr2 expression ...

TY - JOUR. T1 - Role of reelin during layer formation in the cerebralneocortex. AU - Nakajima, Kazunori. PY - 2016/8. Y1 - 2016/8. N2 - Reelin controls the neuronal layer formation in the developing cerebral neocortex. The Reelin glycoprotein is mainly secreted from Cajat-Retzius cells in the marginal zone, and it guides the proper aggregation of the migrating neurons in a birth-dependent inside-out manner. Reelin also regulates the final process of neuronal migration (terminal translocation and somal translocation) by activating integrin and N-cadherin. It is also expressed around the subventricular zone and it controls the behavior of the migrating neurons.. AB - Reelin controls the neuronal layer formation in the developing cerebral neocortex. The Reelin glycoprotein is mainly secreted from Cajat-Retzius cells in the marginal zone, and it guides the proper aggregation of the migrating neurons in a birth-dependent inside-out manner. Reelin also regulates the final process of neuronal ...

Mutations in several genes have now been identified to cause a massive and specific reduction in the total number of neurons in the human brain. The specific ro...

We measured changes in whole-transcriptome expression and in the intrinsic and synaptic physiology of genetically labeled cortical fast-spiking parvalbumin-expressing GABAergic interneurons over the first 6 postnatal weeks. Previous studies have assayed whole-transcriptome expression in rodent neocortex over similar periods of maturation (Semeralul et al., 2006; Stead et al., 2006; Lyckman et al., 2008), but ours is the first to restrict such analysis to a homogeneous subclass of interneurons. In so doing, we were able to reveal cell-type-specific transcriptional changes that are not readily extricable from the overall transcriptional profiles of complex tissues such as the cerebral cortex. We found that 1972 genes were differentially expressed over the span of P7-P40 and that 1124 genes showed an increase in expression, whereas 848 genes showed a decrease. Non-monotonic expression trajectories were rarely observed. This is in contrast to earlier periods of development in which critical sets of ...

Aboitiz, F., and J. Montiel. Origin and Evolution of the Vertebrate Telencephalon, with Special Reference to the Mammalian Neocortex. Advances in Anatomy, Embryology, and Cell Biology, vol. 193, Advances in anatomy, embryology, and cell biology, 2007, pp. 1-112 ...

Rhythmic activity in the neocortex varies with different behavioral and pathological states and in some cases may encode sensory information. However, the neural mechanisms of these oscillations are largely unknown. Many pyramidal neurons in layer 5 of the neocortex showed prolonged, 5- to 12-hertz rhythmic firing patterns at threshold. Rhythmic firing was due to intrinsic membrane properties, sodium conductances were essential for rhythmicity, and calcium-dependent conductances strongly modified rhythmicity. Isolated slices of neocortex generated epochs of 4- to 10-hertz synchronized activity when N-methyl-D-aspartate receptor-mediated channels were facilitated. Layer 5 was both necessary and sufficient to produce these synchronized oscillations. Thus, synaptic networks of intrinsically rhythmic neurons in layer 5 may generate or promote certain synchronized oscillations of the neocortex. ...

The recurrent network composed of excitatory and inhibitory neurons is fundamental to neocortical function. Inhibitory neurons in the mammalian neocortex are molecularly diverse, and individual cell types play unique functional roles in the neocortical microcircuit. Recently, vasoactive intestinal polypeptide-positive (VIP+) neurons, comprising a subclass of inhibitory neurons, have attracted particular attention because they can disinhibit pyramidal cells through inhibition of other types of inhibitory neurons, such as parvalbumin- (PV+) and somatostatin-positive (SOM+) inhibitory neurons, promoting sensory information processing. Although VIP+ neurons have been reported to receive synaptic inputs from PV+ and SOM+ inhibitory neurons as well as from cortical and thalamic excitatory neurons, the somatodendritic localization of these synaptic inputs has yet to be elucidated at subcellular spatial resolution. In the present study, we visualized the somatodendritic membranes of layer (L) 2/3 VIP+ neurons

|p|The generation of neocortical neurons from neural progenitor cells (NPCs) is primarily controlled by transcription factors binding to DNA in the...

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BA #s are the way to go... The cytoarchitectonic subdivisions of both the thalamus and the neocortex are topographically defined in terms of the variables of phylogenetic age and input specificity. The cortical and thalamic parcellations of Brodmann, von Economo and Hassler are each quantitatively correlated to a specific Cartesian coordinate value designating discrete levels for both age and input basic parameters. The variable of phylogenetic age is represented in the cortex by the five circumferential growth rings demonstrated by Sanides, plus an additional growth ring detected intermediate to the fourth and sixth age levels and designated as prekoniocortex. The paleocortex and the archaecortex are the two primordial neocortical precursors that form the mammalian neocortex. In contrast to the arrangement in the planar cortex, six phylogenetically distinct growth shells are detected in the three-dimensional thalamus and are designated after the corresponding schematic levels of Rolf ...

The effect of nicotine 1 nM-10 microM on the efflux of [(3)H]D-aspartate was tested in primary cultures of rat cortical neurons kept at rest and subjected to electrical field stimulation. Two trains of pulses at 20 Hz for 20 s were applied at the 60th (St(1)) and 90th (St(2)) min of perfusion. The drug slightly and transiently increased the efflux of resting cells while, when given during St(2), it greatly enhanced the electrically evoked efflux estimated as St(2)/St(1) ratio, EC(50) being 107 nM. The nicotinic receptors (nAChR) giving rise to this positive modulation were partly mecamylamine- and partly alpha-bungarotoxin-sensitive. They appeared to be located at the nerve endings since nicotine facilitation was only slightly prevented by tetrodotoxin during depolarisation with 15 mM KCl. Pretreatment with glutamate antagonists did not reveal any interaction between nAChR and ionotropic glutamate receptors. Membrane glutamate carrier involvement in the nicotine effect was ruled out. Long-term treatment

For the proper organization of the six-layered mammalian neocortex it is required that neurons migrate radially from their place of birth towards their designated destination. The molecular machinery underlying this neuronal migration is still poorly understood. The dynein-adaptor protein BICD2 is associated with a spectrum of human neurological diseases, including malformations of cortical development. Previous studies have shown that knockdown of BICD2 interferes with interkinetic nuclear migration in radial glial progenitor cells, and that Bicd2-deficient mice display an altered laminar organization of the cerebellum and the neocortex. However, the precise in vivo role of BICD2 in neocortical development remains unclear. By comparing cell-type specific conditional Bicd2 knock-out mice, we found that radial migration in the cortex predominantly depends on BICD2 function in post-mitotic neurons. Neuron-specific Bicd2 cKO mice showed severely impaired radial migration of late-born upper-layer neurons.

The neuronal layers in the neocortex are designated by Roman numerals, beginning at the pial surface (Fig. 32-1). There are six layers in the neocortex, with some of these layers being further subdivided on the basis of their architectural features.. Layer I, the molecular layer, contains very few neuron cell bodies and consists primarily of axons running parallel (horizontal) to the surface of the cortex. The apical dendrites of cells located in deeper layers also ramify within layer I.. Layer II, the external granular layer, is composed of a mixture of small neurons called granule cells and slightly larger neurons that are called pyramidal cells on the basis of the shape of their cell body. The apical dendrites of these pyramidal cells extend into layer I and their axons descend into and through the deeper cortical layers.. Layer III, the external pyramidal layer, contains primarily small to medium-sized pyramidal cells along with some neurons of other types. In general, the smaller pyramidal ...

article{neymotin_human_2020, title = {Human {Neocortical} {Neurosolver} ({HNN}), a new software tool for interpreting the cellular and network origin of human {MEG}/{EEG} data}, volume = {9}, issn = {2050-084X}, url = {https://elifesciences.org/articles/51214}, doi = {10.7554/eLife.51214}, abstract = {Magneto- and electro-encephalography (MEG/EEG) non-invasively record human brain activity with millisecond resolution providing reliable markers of healthy and disease states. Relating these macroscopic signals to underlying cellular- and circuit-level generators is a limitation that constrains using MEG/EEG to reveal novel principles of information processing or to translate findings into new therapies for neuropathology. To address this problem, we built Human Neocortical Neurosolver (HNN, https://hnn.brown.edu) software. HNN has a graphical user interface designed to help researchers and clinicians interpret the neural origins of MEG/EEG. HNNs core is a neocortical circuit model that accounts ...

Other articles where Neocortex is discussed: Nonbiological Man: Hes Closer Than You Think: We will connect our biological neocortex to a synthetic neocortex in the cloud. This will be done by using medical nano-robots that go into the brain through the capillaries and provide wireless communication between our neocortical modules and the cloud in the same way that your smartphone today has wireless…

Chandelier (axoaxonic) cells (ChCs) are a distinct group of GABAergic interneurons that innervate the axon initial segments of pyramidal cells. However, their circuit role and the function of their clearly defined anatomical specificity remain unclear. Recent work has demonstrated that chandelier cells can produce depolarizing GABAergic PSPs, occasionally driving postsynaptic targets to spike. On the other hand, other work suggests that ChCs are hyperpolarizing and may have an inhibitory role. These disparate functional effects may reflect heterogeneity among ChCs. Here, using brain slices from transgenic mouse strains, we first demonstrate that, across different neocortical areas and genetic backgrounds, upper Layer 2/3 ChCs belong to a single electrophysiologically and morphologically defined population, extensively sampling Layer 1 inputs with asymmetric dendrites. Consistent with being a single cell type, we find electrical coupling between ChCs. We then investigate the effect of chandelier cell

The development of antiepileptic drugs critically depends on experimental models that allow testing anticonvulsant effects. Epileptiform activity can be experimentally induced by a variety of methods both in vivo and in vitro, usually by either a reduction of postsynaptic inhibition or by a general increase of spontaneous activity. In vitro, the induction of epileptiform activity in hippocampal or neocortical brain slices can be achieved by an overactivation of postsynaptic NMDA receptors. Usually, NMDA receptors are blocked by Mg2+ ions and this Mg block is only released when postsynaptic neurons are activated through non-NMDA receptors. By reducing the concentration of extracellular Mg2+ ions, epileptiform activity can be easily and reproducibly evoked and antivonvulsant effects of bath-applied compounds can be recorded with minimum experimental effort. Because the hippocampal slice preparation is a well-defined experimental model and the application of Mg2+-free extracellular solutions is ...

Neocortical projection neurons, which segregate into six cortical layers according to their birthdate, have diverse morphologies, axonal projections and molecular profiles, yet they share a common cortical regional identity and glutamatergic neurotransmission phenotype. Here we demonstrate that distinct genetic programs operate at different stages of corticogenesis to specify the properties shared by all neocortical neurons. Ngn1 and Ngn2 are required to specify the cortical (regional), glutamatergic (neurotransmitter) and laminar (temporal) characters of early-born (lower-layer) neurons, while simultaneously repressing an alternative subcortical, GABAergic neuronal phenotype. Subsequently, later-born (upper-layer) cortical neurons are specified in an Ngn-independent manner, requiring instead the synergistic activities of Pax6 and Tlx, which also control a binary choice between cortical/glutamatergic and subcortical/GABAergic fates. Our study thus reveals an unanticipated heterogeneity in the ...

A new study reveals an early relative of mammals possessed an expanded brain with a neocortex like structure. The researchers reported the neocortex like structure developed in a late Permian therapsid 25 million years prior to the emergence of the first mammals.... Read More... ...

Starting from the hypothesis that the mammalian neocortex to a first approximation functions as an associative memory of the attractor network type, we formulate a quantitative computational model of neocortical layers 2/3. The model employs biophysically detailed multi-compartmental model neurons with conductance based synapses and includes pyramidal cells and two types of inhibitory interneurons, i.e., regular spiking non-pyramidal cells and basket cells. The simulated network has a minicolumnar as well as a hypercolumnar modular structure and we propose that minicolumns rather than single cells are the basic computational units in neocortex. The minicolumns are represented in full scale and synaptic input to the different types of model neurons is carefully matched to reproduce experimentally measured values and to allow a quantitative reproduction of single cell recordings. Several key phenomena seen experimentally in vitro and in vivo appear as emergent features of this model. It exhibits a ...

DYRK1A is widely regarded as a candidate gene for mental retardation in DS (Park et al., 2009), but the cellular function of the encoded protein in mammalian brain development is poorly understood. Previous studies demonstrated that Dyrk1A overexpression in transgenic mice consistently results in cognitive dysfunction (Smith and Rubin, 1997; Altafaj et al., 2001; Branchi et al., 2004; Ahn et al., 2006), but the mechanisms underlying the etiology of behavioral defects remained elusive. Dyrk1A is also overexpressed, although to low levels, in DS patients as well as in animal models of DS, such as Ts65Dn mice (Guimera et al., 1999). In this study, we sought to fill a gap in our understanding of the Dyrk1A role in abnormal brain development by investigating the cellular events affected by Dyrk1A overexpression in the developing mouse brain. Our approach has been to overexpress this protein at high levels in the embryonic neocortex in vivo to reveal defective cellular and molecular mechanisms that ...

The local circuits in the neocortex of mammals consists of neurons that need to obtain reliably meaningful information from their dominant activating inputs and to alter their responses to these inputs in relation to inputs that are activating other local cortical circuits. Both of these tasks are mediated by structural features in the neocortex. This chapter discusses the structural features of mammalian neocortex as well as the features that allow dynamic interaction among neurons in different columns. The focus is on the complex variability within and across nervous systems involving neuron densities and proportions to glia and other nonneural cells. The chapter also looks at dendritic arbors of cortical pyramidal cells and how they vary across cortical areas and species, patterns of intrinsic horizontal areal connections, and feedback connections from higher to lower areas in hierarchies of cortical areas.

Article: Neuromodulation by a cytokine: interferon-beta differentially augments neocortical neuronal activity and excitability. ...

It is becoming increasingly clear that the progenitor cells for excitatory neurons are not homogeneous, but rather diverse. In addition to RGCs and IPCs, two new types of neuronal progenitor cells were recently discovered in the developing neocortex: short neural precursors (SNPs) and outer subventricular zone (OSVZ) radial glial progenitors. SNPs maintain their ventricular end-feet but their basal processes are of variable length (Gal et al., 2006) and, unlike RGCs, they generate neurons directly instead of going through an IPC stage (Stancik et al., 2010). OSVZ progenitors, by contrast, maintain the basal processes but lack the apical processes, and are capable of undergoing asymmetric division in the OSVZ. They were initially discovered in humans and later found in primates, ferrets, mice and other species (Fietz et al., 2010; Hansen et al., 2010; Kelava et al., 2012; Shitamukai et al., 2011; Wang et al., 2011). Notably, the abundance of the OSVZ progenitor population and their increased ...

Abstract of 2nd primary source:) The total number of synapses in the human neocortex is approximately 0.15 x 10^15 (0.15 quadrillion). Although the effect of aging is seen in all estimated structural elements, the effect of sex is actually higher. The functional relevance of these differences in neuron numbers in both age and gender is not known. Many useful brain facts and references at the cited website ...

Persistent Na+ channel NEURON { SUFFIX Nap USEION na READ ena WRITE ina RANGE gnapbar, ina, gna RANGE DA_alphamshift,DA_betamshift RANGE DA_alphahfactor, DA_betahfactor } UNITS { (mA) = (milliamp) (mV) = (millivolt) } INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)} PARAMETER { v (mV) dt (ms) gnapbar= 0.0022 (mho/cm2) ,0,1e9, ena = 55 (mV) DA_alphamshift=0 : 2 for 100% DA, 0 otherwise DA_betamshift=0 : 5 for 100% DA,0 otherwise DA_alphahfactor=0: -.8e-5 for DA, 0 otherwise DA_betahfactor=0 : 0.014286-0.02 for DA, 0 otherwise } STATE { m h } ASSIGNED { ina (mA/cm2) minf hinf mtau (ms) htau (ms) gna (mho/cm2) } INITIAL { rate(v) m = minf h = hinf } BREAKPOINT { SOLVE states METHOD cnexp gna = gnapbar*m*h ina = gna*(v-55) } DERIVATIVE states { rate(v) m = (minf-m)/mtau h = (hinf-h)/htau } UNITSOFF FUNCTION malf( v){ LOCAL va va=v+12+DA_alphamshift if (fabs(va),1e-04){ va = va + 0.00001 } malf = (-0.2816*va)/(-1+exp(-va/9.3)) } FUNCTION mbet(v(mV))(/ms) { LOCAL vb vb=v-15+DA_betamshift if (fabs(vb),1e-04){ ...

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Snap-freezing of brain tissue reveals its true structure-showing that cells are less squashed together, and the connections between neurons are less enclosed than previously thought.

Synapsin (SYN) promoter in the vector drives expression of green fluorescent protein (GFP) only in neurons as verified by colocalization with NeuN but not GFAP. Primary murine neocortical cultures containing both neurons and astrocytes were transduced with the lentiviral vector SYN-GFP at an MOI of 5. Seven days after transduction, cultures were fixed and immunostained with anti-NeuN antibody (Chemicon, Alexa 594 secondary antibody) shown in upper 3 panels, or with anti-GFAP antibody (rabbit polyclonal antibody, IncStar, Alexa 594 secondary antibody) shown in lower 3 panels. Left panels show GFP fluorescence, middle panel shows Alexa 594 signal, right panel shows overlay of GFP and immunostaining. Original magnification was 400X. ...

The mammalian neocortex is a sheet of cells covering the cerebrum that provides the structural basis for the perception of sensory inputs, motor output responses, cognitive function, and mental capaci

Id: nqs.hoc,v 1.678 2010/12/13 17:57:28 billl Exp $ // primarily edited in nrniv/place if (!name_declared(VECST_INSTALLED)) { printf(NQS ERROR: Need vecst.mod nmodl package compiled in special.\n) quit() } if (!VECST_INSTALLED) install_vecst() if (! name_declared(datestr)) load_file(setup.hoc) load_file(decvec.hoc) objref g[10] gvmarkflag=0 declared(file_len) strdef execstr,strform strform=%s //* stubs for ancillary programs double sops[21] // AUGMENT TO ADD NEW OPSYM declared(whvarg,whkey,varstr,nqsdel,chsel2,grsel2,oform) proc oformoff () { execute1(func oform(){return NOP}) } // default no operation proc oform64(){execute1(func oform(){{$o1.vpr(64,1)}return OK})} // vec.vpr(64) oformoff() nqsselcp=1 //* NQS template // potential to overwrite XO,tmpfile,i1 begintemplate NQS public cob,out,up // operate on this or out public s,comment,file,v,m,x,ind,scr,fcd,fcds,fcdo,fcdv,fcdl,sstr // strings and vecs public ...

A new study is providing fascinating insight into how projections conveying sensory information in the brain are guided to their appropriate targets in different species. The research, published by Cell Press in the March ...

Great talk Jeff! There are some nice new slides in this deck like this one. Click the slides below to jump to that point in the talk. [01 AM] [19 AM] [06 AM] [08 AM]

Baclofen, 3-amino-propylphosphonic acid (3-APPA), and beta-phenyl-GABA (BPG), each reduced the frequency of spontaneous paroxysmal discharges in rat neocortical slices maintained in Mg2+-free medium, reversibly antagonised by phaclofen and 4-amino-butylphosphonic acid (4-ABPA). At lower concentrations, not influencing the discharges, both 3-APPA and BPG also reversibly antagonised this action of baclofen. However, des-chloro-phaclofen was inactive. Thus, phaclofen and 4-ABPA are GABAB-receptor antagonists in neocortex, whereas both 3-APPA and BPG have partial agonist/antagonist activity at cortical GABAB-receptors.

Dyslexia is one of the most prevalent childhood cognitive disorders, affecting approximately 5% of school-age children. We have recently identified a risk haplotype associated with dyslexia on chromosome 6p22.2 which spans the TTRAP gene and portions of THEM2 and KIAA0319. Here we show that in the presence of the risk haplotype, the expression of the KIAA0319 gene is reduced but the expression of the other two genes remains unaffected. Using in situ hybridization, we detect a very distinct expression pattern of the KIAA0319 gene in the developing cerebral neocortex of mouse and human fetuses. Moreover, interference with rat Kiaa0319 expression in utero leads to impaired neuronal migration in the developing cerebral neocortex. These data suggest a direct link between a specific genetic background and a biological mechanism leading to the development of dyslexia: the risk haplotype on chromosome 6p22.2 down-regulates the KIAA0319 gene which is required for neuronal migration during the formation of the

Regional and cell-type specification during embryogenesis are often coupled to expression of TFs that are restricted to specific progenitor domains. Here, we found that Nkx2-1 restricts the expression of Coup-TF1/2 in the MGE to an arc that extended from a small rostrodorsal domain to a larger caudoventral domain (Fig. 1; Fig. S1B,D,H,K,L). The Coup-TF1/2+ MGE domain was complementary to an Otx2+ domain (Fig. S1B-E), where Otx2 represses Coup-TF1 MGE expression (Hoch et al., 2015a,b).. Our data support a model in which the Coup-TF1/2+ MGE domain is biased towards generating SST+ CINs (Fig. 2; Fig. S3A-C), as well as cholinergic and pallidal neurons (Fig. S4). These conclusions differ from other publications regarding the major location for the origin of SST+ interneurons, and provide evidence for a Coup-TF1/2-dependent activation of Sox6 expression that promotes SST+ interneuron development.. Multiple lines of evidence show that Coup-TF1/2 have key roles in promoting SST+ interneuron ...

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Camp, J.G., Badsha, F., Florio, M. et al.. Cerebral organoids-3D cultures of human cerebral tissue derived from pluripotent stem cells-have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and previously unidentified interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression ...

Previous studies of macaque and human cortices identified cytoarchitectonically distinct germinal zones; the ventricular zone inner subventricular zone (ISVZ), and outer subventricular zone (OSVZ). To date, the OSVZ has only been described in gyrencephalic brains, separated from the ISVZ by an inner fiber layer and considered a milestone that triggered increased neocortical neurogenesis. However, this observation has only been assessed in a handful of species without the identification of the different progenitor populations. We examined the Amazonian rodent agouti (Dasyprocta agouti) and the marmoset monkey (Callithrix jacchus) to further understand relationships among progenitor compartmentalization, proportions of various cortical progenitors, and degree of cortical folding. We identified a similar cytoarchitectonic distinction between the OSVZ and ISVZ at midgestation in both species. In the marmoset, we quantified the ventricular and abventricular divisions and observed similar proportions as

The transcription factor Pax6 has been implicated in neocortical neurogenesis in vertebrates, including humans. Analyses of the role of Pax6 in layer formation and cognitive abilities have been hampered by perinatal lethality of Pax6 mutants. Here, we generated viable mutants exhibiting timed, restricted inactivation of Pax6 during early and late cortical neurogenesis using Emx1-Cre and hGFAP-Cre lines, respectively. The disruption of Pax6 at the onset of neurogenesis using Emx1-Cre line resulted in premature cell cycle exit of early progenitors, increase of early born neuronal subsets located in the marginal zone and lower layers, and a nearly complete absence of upper layer neurons, especially in the rostral cortex. Furthermore, progenitors, which accumulated in the enlarged germinal neuroepithelium at the pallial/subpallial border in the Pax6 mutants, produced an excess of oligodendrocytes. The inactivation of Pax6 after generation of the lower neuronal layers using hGFAP-Cre line did not affect

Yun, C.H.; Lee, S.K.n; Chung, C.K.; Kim, K.K., 2003: Surgical outcome and prognostic factors in medically intractable neocortical epilepsy

From Popular Mechanics:. Researchers from Germanys Max Planck Institute of Molecular Cell Biology and Genetics in Germany and Japans Central Institute for Experimental Animals introduced a specifically human gene,ARHGAP11B, into the fetus of a common marmoset monkey, causing the enlargement of its brains neocortex. The scientistsreported their findings in Science.. Those findings include a good indication that the ARHGAP11B gene played a key role in the development of the human neocortex, and, by extension, human evolution overall. (A 2015 study saw similar results with ARHGAP11B implanted in mice embryos, which produced many more neural progenitor cells and could even undergo folding of their normally unfolded neocortex.). In a press alert, the scientists behind the study were careful to specifically refer to their subjects as transgenic non-human primates, which differentiates them from transgenic common marmosets, or humans (were not given a cool classification for the sake of ...

Cortical activity during sleep and waking is traditionally investigated with electroencephalography (EEG). The most distinctive feature of neocortical activity during sleep is the occurrence of EEG slow waves, arising from quasi-synchronous periods of activity and silence among cortical neurons. The EEG slow waves are regulated homeostatically: they are larger and have a higher incidence following long waking periods and decrease as a function of time spent asleep. Since intense early sleep seems to be important for restoration, understanding the cellular mechanisms underlying homeostatic regulation of sleep slow waves may appear crucial for understanding sleep function. While macrooscillations recorded with the EEG arise from synchronous activity and silence of large populations of cortical neurons, at present intracellular recording techniques do not allow monitoring the state of more than just a few cells at a time across spontaneous sleep-wake cycle in unrestrained animals. Here, we review a ...

At last we come to the neomammalian complex (or cerebral neocortex). This third part of the brain is represented in the hand model by the fingers and top surface of the hand.

At last we come to the neomammalian complex (or cerebral neocortex). This third part of the brain is represented in the hand model by the fingers and top surface of the hand.

Early separation of rat pups from their mothers (|i|separatio a matrem|/i|) is considered and accepted as an animal model of perinatal stress. Adult rats, separated early postnatally from their mothers, are developing long-lasting changes in the brain and neuroendocrine system, corresponding to the findings observed in schizophrenia and affective disorders. With the aim to investigate the morphological changes in this animal model we exposed 9-day-old (P9) Wistar rats to a 24 h maternal deprivation (MD). At young adult age rats were sacrificed for morphometric analysis and their brains were compared with the control group bred under the same conditions, but without MD. Rats exposed to MD had a 28% smaller cell soma area in the prefrontal cortex (PFCX), 30% in retrosplenial cortex (RSCX), and 15% in motor cortex (MCX) compared to the controls. No difference was observed in the expression of glial fibrillary acidic protein in the neocortex of MD rats compared to the control group.

The reliability and temporal precision of signal propagation between neurons is a major constraint for different coding strategies in neuronal networks. In systems that rely on rate coding, input-output functions of neurons are classically described as ratios of mean firing rates, and the precise timing of individual action potentials is not considered a meaningful parameter (Shadlen and Newsome, 1994, 1998). In these systems, synchrony of presynaptic action potentials and reliable synaptic transmission have even been implicated to deteriorate the information content of the postsynaptic spike train (Zador, 1998). For the functioning of a temporal code in neuronal networks, on the other hand, the precision and reliability of synaptic integration is a prerequisite (Abeles, 1991; Konig et al., 1996; Mainen and Sejnowski, 1995; Nowak et al., 1997; Roy and Alloway, 2001), and without exact spike timing in the millisecond range, synchronous activity among neurons that putatively form a functional cell ...

The forebrain embryonic zinc finger-like (Fez) family of transcription factors is expressed mainly in the mouse adult neocortex. Fezf1 is a transcription repressor that is essential for axonal projection and proper termination of olfactory sensory neurons (OSNs). It plays a role in patterning of the diencephalon and in prethalamic formation. Knockout of the Fezf1 gene in mice resulted in impaired olfactory bulb development neonatal lethality. Fezf1 is also known as zinc finger protein 312B (ZFP312B), fez family zinc finger protein 1, and Fez.. ...

Scientists at The Scripps Research Institute (TSRI) have decoded an important molecular signal that guides the development of a key region of the brain known as the neocortex. The largest and most recently evolved region of the brain, the neocortex is particularly well developed in humans and is responsible for sensory processing, long-term memory, reasoning, complex muscle actions, consciousness and other functions.. The mammalian neocortex has a distinctive structure featuring six layers of neurons, and our finding helps explain how this layered structure is generated in early life, said Ulrich Mueller, chair of TSRIs Department of Molecular and Cellular Neuroscience and director of the Dorris Neuroscience Center at TSRI.. The discovery, which appears in the August 7, 2013 issue of Neuron, also is likely to aid research on autism, schizophrenia and other psychiatric conditions. With studies such as this one, were starting to understand the normal functions of molecules whose disruption by ...

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It has been unclear whether ischemic stroke induces neurogenesis or neuronal DNA rearrangements in the human neocortex. Using immunohistochemistry; transcriptome, genome and ploidy analyses; and determination of nuclear bomb test-derived (14)C concentration in neuronal DNA, we found neither to be the case. A large proportion of cortical neurons displayed DNA fragmentation and DNA repair a short time after stroke, whereas neurons at chronic stages after stroke showed DNA integrity, demonstrating the relevance of an intact genome for survival.. ...

Our research focuses on studying brain transcriptome using next-generation sequencing, in particular, RNA-Seq technique. We are interested in region-specific gene expression profiles in brain development and ageing as well as perturbation of the transcriptome as a result of neurodegeneration.. Recent advances in genomic technology allowed to uncover new RNA species, circular RNAs (circRNAs; Fig. 1). CircRNAs have been identified as a naturally occurring family of widespread and diverse endogenous noncoding RNAs that may regulate gene expression in mammals (Huang et al. 2017) and are perturbed as a result of neurodegeneration (Chen et al. 2016). They are unusually stable RNA molecules with cell type- or developmental stage-specific expression patterns. However, the role of circRNAs in molecular biology of the brain remains unknown. Hence, the aim of this project is to investigate changes in circRNA expression signatures in mouse and human neocortex. The second research aim is to discover new ...

When you think about it, the real difference between animals and ourselves is that although we both experience stress, humans re-experience and pre-experience traumatic situations. The above quote from my first book, Evolve Your Brain, sparked a healthy conversation on my Facebook page recently. As promised, Im going to discuss this material in an effort to provide a little clarity and understanding. Let me start by saying that the intent of this passage is to illustrate our ability to create reality with our minds. The human neocortex is an amazing instrument that helps us learn and remember. This is [...]. ...

Much attention has focused on the dramatic expansion of the forebrain, particularly the neocortex, as the neural substrate of cognitive evolution. However, though relatively small, the cerebellum contains about four times more neurons than the neocortex. I show that commonly used comparative measures such as neocortex ratio underestimate the contribution of the cerebellum to brain evolution. Once differences in the scaling of connectivity in neocortex and cerebellum are accounted for, a marked and general pattern of correlated evolution of the two structures is apparent. One deviation from this general pattern is a relative expansion of the cerebellum in apes and other extractive foragers. The confluence of these comparative patterns, studies of ape foraging skills and social learning, and recent evidence on the cognitive neuroscience of the cerebellum, suggest an important role for the cerebellum in the evolution of the capacity for planning, execution and understanding of complex behavioural ...

PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

The mammalian neocortex is characterized by a variety of neuronal cell types and precise arrangements of synaptic connections, but the processes that generate this diversity are poorly understood. Here we examine how a pool of embryonic progenitor cells consisting of apical intermediate progenitors (aIPs) contribute to diversity within the upper layers of mouse cortex. In utero labeling combined with single-cell RNA-sequencing reveals that aIPs can generate transcriptionally defined glutamatergic cell types, when compared to neighboring neurons born from other embryonic progenitor pools. Whilst sharing layer-associated morphological and functional properties, simultaneous patch clamp recordings and optogenetic studies reveal that aIP-derived neurons exhibit systematic biases in both their intralaminar monosynaptic connectivity and the post-synaptic partners that they target within deeper layers of cortex. Multiple cortical progenitor pools therefore represent an important factor in establishing

The neocortex is the part of the brain that is involved in perception, cognition, and volitional motor control. In mammals it is a highly dynamic structure that has been dramatically altered within an individuals lifetime and in different lineages throughout the course of evolution. These alterations account for the remarkable variations in behavior that species exhibit. Because we cannot study the evolution of the neocortex directly, we must make inferences about the evolutionary process from a comparative analysis of brains, and study the developmental mechanisms that give rise to alterations in the brain. Comparative studies allow us to appreciate the types of changes that have been made to the neocortex and the similarities that exist across taxa, and ultimately the constraints imposed on the evolving brain. Developmental studies inform us about how phenotypic transitions may arise by alterations in developmental cascades or changes in the physical environment in which the brain develops. ...

1) Neocortex - the whole large sheet of brain cells on the brains outer surface, folded up into the skull giving it the appearance of a walnut.. 2) Frontal lobe - the region of the neocortex at the front of the brain, behind the forehead, which is much larger in humans than our monkey cousins and enables us to do all those complex functions that other primates cannot.. 3) Brainstem - the part of the brain that ninja assasins aim for with their deadly chop where neck meets skull, it is involved in coordinating all the vital bodily functions that keep us alive e.g. breathing and heart rates.. 4) Hippocampus - key brain area at the core of the temporal lobes (which run horizontally down the sides of the head from the temple to behind the ears) which is heavily involved in not just creating, but also retrieving memories. It also creates new brain cells in response to exercise!. 5) Neural node - erm, I think they just needed something sciency sounding to rhyme with the other lines. The image THE ...

Our ability to perceive and respond to our environment requires the brain to build representations of the outside world. How does the brain do this?. A key function of the brain is to extract features of the sensory environment (e.g., through vision, audition, olfaction) and use them to build more complex abstract representations (e.g., a sense of space). Research groups at the SWC focus on understanding the computations that give rise to these representations and how these computations map onto the underlying neural circuits.. In many instances, sensory and abstract representations of the outside world are used to inform motor actions. SWC studies how neocortex, basal ganglia, midbrain, cerebellum, brainstem and spinal circuits coordinate sensory-motor computations to obtain general insights into how sensory information is transformed into meaningful actions.. For this purpose, SWC researchers record from hundreds of neurons using multi-channel electrodes (e.g. Neuropixels probes) or two-photon ...

A newly discovered set of genes could help explain how humans diverged from other apes.. Three genes involved in nerve cell generation in the brain emerged roughly 3.5 million years ago and may have contributed to the rapid evolution of the large human brain, Howard Hughes Medical Institute (HHMI) Investigator David Haussler and colleagues report on May 31, 2018, in the journal Cell. That work - and a paper from an independent research team published in the same issue - identifies genes that help build the neocortex, the wrinkly outer layer of the brain that gives humans our ability to think, plan, and reason.. Until now, the genes had been unexplored, masked by an error in the published version of the human genome. These genes, and others unique to humans, offer clues about what separates us from chimpanzees, says Haussler, of the University of California, Santa Cruz (UCSC).. Understanding ourselves and how were different from other species has been a scientific quest for millennia, he says. ...

Zhongyang Lu is the author of this article in the Journal of Visualized Experiments: Targeted Labeling of Neurons in a Specific Functional Micro-domain of the Neocortex by Combining Intrinsic Signal and Two-photon Imaging

Me: http://www.digitalkingdom.org/~rlpowell/ *** Im a *male* Robin. Constant neocortex override is the only thing that stops us all from running out and eating all the cookies. -- Eliezer Yudkowsky http://www.lojban.org/ *** .i cimoo prali .ui ...