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On the origin of neurons
Jeremy N Pulvers, Judith Schenk, Yoko Arai, Ji-Feng Fei, Kanako Saito, Wieland B Huttner
Genome Biology , 2007, DOI: 10.1186/gb-2007-8-7-311
Abstract: The understanding of embryonic and adult neurogenesis, and their possible medical applications, are highly active fields of research, as became evident at the first international meeting devoted solely to mammalian brain neurogenesis, entitled 'Neurogenesis 2007' and held at the National Museum of Emerging Science and Innovation in Tokyo this May. Exciting new insights into neurogenesis were presented and discussed, encompassing many aspects of neuron generation, such as progenitor cell division, neuronal migration, adult neurogenesis, and stem-cell therapy. The dissection of these processes ranged from detailed cell biological analyses to the unraveling of transcriptional networks. Here we report a few of the highlights of the conference.During the development of the mammalian brain, neurons arise from neural stem and progenitor cells, which initially proliferate by symmetric divisions and later switch to both asymmetric and symmetric neurogenic divisions. In the dorsal telencephalon of the embryo, newborn neurons migrate radially to the developing six-layered cerebral cortex. Multiple types of progenitors exist with different cell biological characteristics and modes of division. To control the number, type, and final location of neurons, the transition from proliferative to neurogenic cell divisions requires a complex network of regulation so that neural specification, cell-cycle exit, cell differentiation and neuronal migration can all occur in concert. Subsequently, in the adult brain, a subset of astrocyte-like cells remains as stem cells in the sub-ventricular zone of the lateral ventricle and dentate gyrus of the hippocampus, giving rise to neuronal progenitors that produce neurons throughout life.Neuronal progenitors in the dorsal telencephalon of rodent embryos fall into two major classes: those that divide at the apical surface (neuroepithelial and radial glial cells, collectively referred to as apical progenitors) and those that divide at the basal side
Serotonin modulation of cortical neurons and networks  [PDF]
Pau Celada,M. Victoria Puig,Francesc Artigas
Frontiers in Integrative Neuroscience , 2013, DOI: 10.3389/fnint.2013.00025
Abstract: The serotonergic pathways originating in the dorsal and median raphe nuclei (DR and MnR, respectively) are critically involved in cortical function. Serotonin (5-HT), acting on postsynaptic and presynaptic receptors, is involved in cognition, mood, impulse control and motor functions by (1) modulating the activity of different neuronal types, and (2) varying the release of other neurotransmitters, such as glutamate, GABA, acetylcholine and dopamine. Also, 5-HT seems to play an important role in cortical development. Of all cortical regions, the frontal lobe is the area most enriched in serotonergic axons and 5-HT receptors. 5-HT and selective receptor agonists modulate the excitability of cortical neurons and their discharge rate through the activation of several receptor subtypes, of which the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT3 subtypes play a major role. Little is known, however, on the role of other excitatory receptors moderately expressed in cortical areas, such as 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro and in vivo studies suggest that 5-HT1A and 5-HT2A receptors are key players and exert opposite effects on the activity of pyramidal neurons in the medial prefrontal cortex (mPFC). The activation of 5-HT1A receptors in mPFC hyperpolarizes pyramidal neurons whereas that of 5-HT2A receptors results in neuronal depolarization, reduction of the afterhyperpolarization and increase of excitatory postsynaptic currents (EPSCs) and of discharge rate. 5-HT can also stimulate excitatory (5-HT2A and 5-HT3) and inhibitory (5-HT1A) receptors in GABA interneurons to modulate synaptic GABA inputs onto pyramidal neurons. Likewise, the pharmacological manipulation of various 5-HT receptors alters oscillatory activity in PFC, suggesting that 5-HT is also involved in the control of cortical network activity. A better understanding of the actions of 5-HT in PFC may help to develop treatments for mood and cognitive disorders associated with an abnormal function of the frontal lobe.
The origin of neocortical nitric oxide synthase-expressing inhibitory neurons  [PDF]
Xavier H. Jaglin,Jens Hjerling-Leffler,Renata Batista-Brito
Frontiers in Neural Circuits , 2012, DOI: 10.3389/fncir.2012.00044
Abstract: Inhibitory neurons are critical for regulating effective transfer of sensory information and network stability. The precision of inhibitory function likely derives from the existence of a variety of interneuron subtypes. Their specification is largely dependent on the locale of origin of interneuron progenitors. Neocortical and hippocampal inhibitory neurons originate the subpallium, namely in the medial and caudal ganglionic eminences (MGE and CGE), and in the preoptic area (POA). In the hippocampus, neuronal nitric oxide synthase (nNOS)-expressing cells constitute a numerically large GABAergic interneuron population. On the contrary, nNOS-expressing inhibitory neurons constitute the smallest of the known neocortical GABAergic neuronal subtypes. The origins of most neocortical GABAergic neuron subtypes have been thoroughly investigated, however, very little is known about the origin of, or the genetic programs underlying the development of nNOS neurons. Here, we show that the vast majority of neocortical nNOS-expressing neurons arise from the MGE rather than the CGE. Regarding their molecular signature, virtually all neocortical nNOS neurons co-express the neuropeptides somatostatin (SST) and neuropeptide Y (NPY), and about half of them express the calcium-binding protein calretinin (CR). nNOS neurons thus constitute a small cohort of the MGE-derived SST-expressing population of cortical inhibitory neurons. Finally, we show that conditional removal of the transcription factor Sox6 in MGE-derived GABAergic cortical neurons results in an absence of SST and CR expression, as well as reduced expression of nNOS in neocortical nNOS neurons. Based on their respective abundance, origin and molecular signature, our results suggest that neocortical and hippocampal nNOS GABAergic neurons likely subserve different functions and have very different physiological relevance in these two cortical structures.
Roles of Integrins and Intracellular Molecules in the Migration and Neuritogenesis of Fetal Cortical Neurons: MEK Regulates Only the Neuritogenesis  [PDF]
Ujjwal K. Rout
Neuroscience Journal , 2013, DOI: 10.1155/2013/859257
Abstract: The roles of integrin subunits and intracellular molecules in regulating the migration and neuritogenesis of neurons isolated from 16.5 gestation days rat fetal cortices were examined using in vitro assays. Results showed that laminin supported the migration of fetal cortical neurons better than fibronectin and that the fetal cortical neurons migrated on laminin using β1 and α3 integrin subunits which make up the α3β1 integrin receptor. On fibronectin, the migration was mediated by β1 integrin subunit. Perturbation of src kinase, phospholipase C, or protein kinase C activity, inhibition of IP3 receptor mediated calcium release, or chelation of intracellular calcium inhibited both migration and neuritogenesis, whereas inhibition of growth factor signaling via MEK inhibited only the neuritogenesis. The detection of α1 and α9 transcripts suggested that the migration of fetal cortical neurons may also be mediated by α1β1 and α9β1 integrin receptors. Results showed that calcium may regulate migration and neuritogenesis by maintaining optimum levels of microtubules in the fetal cortical neurons. It is concluded that the fetal cortical neurons are fully equipped with the integrin signaling cascade required for their migration and neuritogenesis, whereas crosstalk between the integrin and growth-factor signaling regulate only the neuritogenesis. 1. Introduction During brain development, postmitotic neurons migrate from their site of origin to distant places, differentiate, and make connections forming different layers of the cortex. Defects in this process results in abnormal neuronal positioning and connections in the brain, which may cause neurobehavioral problems later in life [1]. Neuritogenesis, an early step of neuron differentiation, is the synthesis of multiple growth cone tipped extensions (neurites) that ultimately form the axons and dendrites of neurons [2]. Mechanisms that regulate the migration and differentiation of neurons are not fully understood. Cell surface integrin receptors, each consisting of an α and a β subunit, play critical roles in the glial-guided migration of neurons in the brain [3]. The extracellular domains of the receptor subunits bind with extracellular matrix (ECM) proteins (such as fibronectin and laminin) and the cytosolic domains of β subunits interact with kinases, adaptor molecules, and the cytoskeleton [4]. These interactions facilitate the “outside-in” and the “inside-out” signaling across the cell membrane by the integrin heterodimers [5] that may lead to cell migration and neuritogenesis [6]. Integrin receptors with
Inferring network properties of cortical neurons with synaptic coupling and parameter dispersion  [PDF]
Dipanjan Roy,Viktor Jirsa
Frontiers in Computational Neuroscience , 2013, DOI: 10.3389/fncom.2013.00020
Abstract: Computational models at different space-time scales allow us to understand the fundamental mechanisms that govern neural processes and relate uniquely these processes to neuroscience data. In this work, we propose a novel neurocomputational unit (a mesoscopic model which tell us about the interaction between local cortical nodes in a large scale neural mass model) of bursters that qualitatively captures the complex dynamics exhibited by a full network of parabolic bursting neurons. We observe that the temporal dynamics and fluctuation of mean synaptic action term exhibits a high degree of correlation with the spike/burst activity of our population. With heterogeneity in the applied drive and mean synaptic coupling derived from fast excitatory synapse approximations we observe long term behavior in our population dynamics such as partial oscillations, incoherence, and synchrony. In order to understand the origin of multistability at the population level as a function of mean synaptic coupling and heterogeneity in the firing rate threshold we employ a simple generative model for parabolic bursting recently proposed by Ghosh et al. (2009). Further, we use here a mean coupling formulated for fast spiking neurons for our analysis of generic model. Stability analysis of this mean field network allow us to identify all the relevant network states found in the detailed biophysical model. We derive here analytically several boundary solutions, a result which holds for any number of spikes per burst. These findings illustrate the role of oscillations occurring at slow time scales (bursts) on the global behavior of the network.
Properties of bilateral spinocerebellar activation of cerebellar cortical neurons  [PDF]
Pontus Geborek,Fredrik Bengtsson,Henrik J?rntell
Frontiers in Neural Circuits , 2014, DOI: 10.3389/fncir.2014.00128
Abstract: We aimed to explore the cerebellar cortical inputs from two spinocerebellar pathways, the spinal border cell-component of the ventral spinocerebellar tract (SBC-VSCT) and the dorsal spinocerebellar tract (DSCT), respectively, in the sublobule C1 of the cerebellar posterior lobe. The two pathways were activated by electrical stimulation of the contralateral lateral funiculus (coLF) and the ipsilateral LF (iLF) at lower thoracic levels. Most granule cells in sublobule C1 did not respond at all but part of the granule cell population displayed high-intensity responses to either coLF or iLF stimulation. As a rule, Golgi cells and Purkinje cell simple spikes responded to input from both LFs, although Golgi cells could be more selective. In addition, a small population of granule cells responded to input from both the coLF and the iLF. However, in these cases, similarities in the temporal topography and magnitude of the responses suggested that the same axons were stimulated from the two LFs, i.e., that the axons of individual spinocerebellar neurons could be present in both funiculi. This was also confirmed for a population of spinal neurons located within known locations of SBC-VSCT neurons and dorsal horn (dh) DSCT neurons. We conclude that bilateral spinocerebellar responses can occur in cerebellar granule cells, but the VSCT and DSCT systems that provide the input can also be organized bilaterally. The implications for the traditional functional separation of VSCT and DSCT systems and the issue whether granule cells primarily integrate functionally similar information or not are discussed.
Morphometric characteristics of Neuropeptide Y immunoreactive neurons of human cortical amygdaloid nucleus  [PDF]
Mali? Milo?,Nikoli? Valentina,?uleji? Vuk,Opri? Dejan
Medicinski Pregled , 2008, DOI: 10.2298/mpns0806235m
Abstract: Introduction Cortical amygdaloid nucleus belongs to the corticomedial part of the amygdaloid complex. In this nucleus there are neurons that produce neuropetide Y. This peptide has important roles in sleeping, learning, memory, gastrointestinal regulation, anxiety, epilepsy, alcoholism and depression. Material and methods We investigated morphometric characteristics (numbers of primary dendrites, longer and shorter diameters of cell bodies and maximal radius of dendritic arborization) of NPY immunoreactive neurons of human cortical amygdaloid nucleus on 6 male adult human brains, aged 46 to 77 years, by immunohistochemical avidin-biotin technique. Results Our investigation has shown that in this nucleus there is a moderate number of NPY immunoreactive neurons. 67% of found neurons were nonpyramidal, while 33% were pyramidal. Among the nonpyramidal neurons the dominant groups were multipolar neurons (41% - of which 25% were multipolar irregular, and 16% multipolar oval). Among the pyramidal neurons the dominant groups were the neurons with triangular shape of cell body (21%). All found NPY immunoreactive neurons (pyramidal and nonpyramidal altogether) had intervals of values of numbers of primary dendrites 2 to 6, longer diameters of cell bodies 13 to 38 μm, shorter diameters of cell bodies 9 to 20 μm and maximal radius of dendritic arborization 50 to 340 μm. More than a half of investigated neurons (57%) had 3 primary dendrites. Discussion and conclusion The other researchers did not find such percentage of pyramidal immunoreactive neurons in this amygdaloid nucleus. If we compare our results with the results of the ather researchers we can conclude that all pyramidal NPY immunoreactive neurons found in this human amygdaloid nucleus belong to the class I of neurons, and that all nonpyramidal NPY immunoreactive neurons belong to the class II of neurons described by other researchers. We suppose that all found pyramidal neurons were projectional.
Columnar distribution of activity dependent gabaergic depolarization in sensorimotor cortical neurons  [cached]
Lee Jaekwang,Woo Junsung,Favorov Oleg V,Tommerdahl Mark
Molecular Brain , 2012, DOI: 10.1186/1756-6606-5-33
Abstract: Background GABA, the major inhibitory neurotransmitter in CNS, has been demonstrated to paradoxically produce excitation even in mature brain. However activity-dependent form of GABA excitation in cortical neurons has not been observed. Here we report that after an intense electrical stimulation adult cortical neurons displayed a transient GABA excitation that lasted for about 30s. Results Whole-cell patch recordings were performed to evaluate the effects of briefly applied GABA on pyramidal neurons in adult rodent sensorimotor cortical slice before and after 1 s, 20 Hz suprathreshold electrical stimulation of the junction between layer 6 and the underlying white matter (L6/WM stimulation). Immediately after L6/WM stimulation, GABA puffs produced neuronal depolarization in the center of the column-shaped region. However, both prior to or 30s after stimulation GABA puffs produced hyperpolarization of neurons. 2-photon imaging in neurons infected with adenovirus carrying a chloride sensor Clomeleon revealed that GABA induced depolarization is due to an increase in [Cl-]i after stimulation. To reveal the spatial extent of excitatory action of GABA, isoguvacine, a GABAA receptors agonist, was applied right after stimulation while monitoring the intracellular Ca2+ concentration in pyramidal neurons. Isoguvacine induced an increase in [Ca2+]i in pyramidal neurons especially in the center of the column but not in the peripheral regions of the column. The global pattern of the Ca2+ signal showed a column-shaped distribution along the stimulation site. Conclusion These results demonstrate that the well-known inhibitory transmitter GABA rapidly switches from hyperpolarization to depolarization upon synaptic activity in adult somatosensory cortical neurons.
Synthetic reverberating activity patterns embedded in networks of cortical neurons  [PDF]
Roni Vardi,Avner Wallach,Evi Kopelowitz,Moshe Abeles,Shimon Marom,Ido Kanter
Quantitative Biology , 2012, DOI: 10.1209/0295-5075/97/66002
Abstract: Synthetic reverberating activity patterns are experimentally generated by stimulation of a subset of neurons embedded in a spontaneously active network of cortical cells in-vitro. The neurons are artificially connected by means of conditional stimulation matrix, forming a synthetic local circuit with a predefined programmable connectivity and time-delays. Possible uses of this experimental design are demonstrated, analyzing the sensitivity of these deterministic activity patterns to transmission delays and to the nature of ongoing network dynamics.
Synchronized dynamics of cortical neurons with time-delay feedback  [cached]
Landsman Alexandra S,Schwartz Ira B
Nonlinear Biomedical Physics , 2007, DOI: 10.1186/1753-4631-1-2
Abstract: The dynamics of three mutually coupled cortical neurons with time delays in the coupling are explored numerically and analytically. The neurons are coupled in a line, with the middle neuron sending a somewhat stronger projection to the outer neurons than the feedback it receives, to model for instance the relay of a signal from primary to higher cortical areas. For a given coupling architecture, the delays introduce correlations in the time series at the time-scale of the delay. It was found that the middle neuron leads the outer ones by the delay time, while the outer neurons are synchronized with zero lag times. Synchronization is found to be highly dependent on the synaptic time constant, with faster synapses increasing both the degree of synchronization and the firing rate. Analysis shows that pre-synaptic input during the inter-spike interval stabilizes the synchronous state, even for arbitrarily weak coupling, and independent of the initial phase. The finding may be of significance to synchronization of large groups of cells in the cortex that are spatially distanced from each other.
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