Browsing by Subject "CEREBRAL-CORTEX"

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  • Sharifian, Fariba; Heikkinen, Hanna; Vigrio, Ricardo; Vanni, Simo (2016)
    In the visual cortex, stimuli outside the classical receptive field (CRF) modulate the neural firing rate, without driving the neuron by themselves. In the primary visual cortex (V1), such contextual modulation can be parametrized with an area summation function (ASF): increasing stimulus size causes first an increase and then a decrease of firing rate before reaching an asymptote. Earlier work has reported increase of sparseness when CRF stimulation is extended to its surroundings. However, there has been no clear connection between the ASF and network efficiency. Here we aimed to investigate possible link between ASF and network efficiency. In this study, we simulated the responses of a biomimetic spiking neural network model of the visual cortex to a set of natural images. We varied the network parameters, and compared the Vi excitatory neuron spike responses to the corresponding responses predicted from earlier single neuron data from primate visual cortex. The network efficiency was quantified with firing rate (which has direct association to neural energy consumption), entropy per spike and population sparseness. All three measures together provided a clear association between the network efficiency and the ASF. The association was clear when varying the horizontal connectivity within V-1, which influenced both the efficiency and the distance to ASF, DAS. Given the limitations of our biophysical model, this association is qualitative, but nevertheless suggests that an ASF-like receptive field structure can cause efficient population response.
  • Hyvärinen, Tanja; Hyysalo, Anu; Kapucu, Fikret Emre; Aarnos, Laura; Vinogradov, Andrey; Eglen, Stephen J.; Ylä-Outinen, Laura; Narkilahti, Susanna (2019)
    Human pluripotent stem cell (hPSC)-derived neurons provide exciting opportunities for in vitro modeling of neurological diseases and for advancing drug development and neurotoxicological studies. However, generating electrophysiologically mature neuronal networks from hPSCs has been challenging. Here, we report the differentiation of functionally active hPSC-derived cortical networks on defined laminin-521 substrate. We apply microelectrode array (MEA) measurements to assess network events and compare the activity development of hPSC-derived networks to that of widely used rat embryonic cortical cultures. In both of these networks, activity developed through a similar sequence of stages and time frames; however, the hPSC-derived networks showed unique patterns of bursting activity. The hPSC-derived networks developed synchronous activity, which involved glutamatergic and GABAergic inputs, recapitulating the classical cortical activity also observed in rodent counterparts. Principal component analysis (PCA) based on spike rates, network synchronization and burst features revealed the segregation of hPSC-derived and rat network recordings into different clusters, reflecting the species-specific and maturation state differences between the two networks. Overall, hPSC-derived neural cultures produced with a defined protocol generate cortical type network activity, which validates their applicability as a human-specific model for pharmacological studies and modeling network dysfunctions.
  • Bhandage, Amol K.; Jin, Zhe; Bazov, Igor; Kononenko, Olga; Bakalkin, Georgy; Korpi, Esa R.; Birnir, Bryndis (2014)
  • Hatch, Robert J.; Mendis, G. Dulini C.; Kaila, Kai; Reid, Christopher A.; Petrou, Steven (2017)
    Gap junctions form electrical synapses that modulate neuronal activity by synchronizing action potential (AP) firing of cortical interneurons (INs). Gap junctions are thought to form predominantly within cortical INs of the same functional class and are therefore considered to act within discrete neuronal populations. Here, we challenge that view and show that the probability of electrical coupling is the same within and between regularspiking (RS) and fast-spiking (FS) cortical INs in 16-21 days old mice. Firing properties of these two populations were distinct from other INs types including neurogliaform and low-threshold spiking (LTS) cells. We also demonstrate that pre-junctional APs can depolarize post-junctional neurons and increase the probability of firing. Our findings of frequent gap junction coupling between functionally distinct IN subtypes suggest that cortical IN networks are much more extensive and heterogeneous than previously thought. This may have implications on mechanisms ranging from cognitive functions to modulation of pathological states in epilepsy and other neurological disorders.
  • Darki, Fahimeh; Massinen, Satu; Salmela, Elina; Matsson, Hans; Peyrard-Janvid, Myriam; Klingberg, Torkel; Kere, Juha (2017)
    The axon guidance receptor, Robo1, controls the pathfinding of callosal axons in mice. To determine whether the orthologous ROBO1 gene is involved in callosal development also in humans, we studied polymorphisms in the ROBO1 gene and variation in the white matter structure in the corpus callosum using both structural magnetic resonance imaging and diffusion tensor magnetic resonance imaging. We found that five polymorphisms in the regulatory region of ROBO1 were associated with white matter density in the posterior part of the corpus callosum pathways. One of the polymorphisms, rs7631357, was also significantly associated with the probability of connections to the parietal cortical regions. Our results demonstrate that human ROBO1 may be involved in the regulation of the structure and connectivity of posterior part of corpus callosum.
  • Eising, Else; de Leeuw, Christiaan; Min, Josine L.; Anttila, Verneri; Verheijen, Mark H. G.; Terwindt, Gisela M.; Dichgans, Martin; Freilinger, Tobias; Kubisch, Christian; Ferrari, Michel D.; Smit, August B.; de Vries, Boukje; Palotie, Aarno; van den Maagdenberg, Arn M. J. M.; Posthuma, Danielle; Int Headache Genetics Consortium (2016)
    Background Migraine is a common episodic brain disorder characterized by recurrent attacks of severe unilateral headache and additional neurological symptoms. Two main migraine types can be distinguished based on the presence of aura symptoms that can accompany the headache: migraine with aura and migraine without aura. Multiple genetic and environmental factors confer disease susceptibility. Recent genome-wide association studies (GWAS) indicate that migraine susceptibility genes are involved in various pathways, including neurotransmission, which have already been implicated in genetic studies of monogenic familial hemiplegic migraine, a subtype of migraine with aura. Methods To further explore the genetic background of migraine, we performed a gene set analysis of migraine GWAS data of 4954 clinic-based patients with migraine, as well as 13,390 controls. Curated sets of synaptic genes and sets of genes predominantly expressed in three glial cell types (astrocytes, microglia and oligodendrocytes) were investigated. Discussion Our results show that gene sets containing astrocyte- and oligodendrocyte-related genes are associated with migraine, which is especially true for gene sets involved in protein modification and signal transduction. Observed differences between migraine with aura and migraine without aura indicate that both migraine types, at least in part, seem to have a different genetic background.
  • Putkinen, Vesa; Saarikivi, Katri (2018)
    Musical training has been associated with superior performance in various executive function tasks. To date, only a few neuroimaging studies have investigated the neural substrates of the supposed "musician advantage" in executive functions, precluding definite conclusions about its neural basis. Here, we provide a selective review of neuroimaging studies on plasticity and typical maturation of executive functions, with the aim of investigating how proficient performance in executive function tasks is reflected in brain activity. Specifically, we examine the evidence for the hypothesis that enhanced or mature executive functions are manifested as efficient use of neural systems supporting those functions. We also present preliminary results from a functional magnetic resonance imaging study suggesting-in line with this hypothesis-that musically trained adolescents recruit frontoparietal regions less strongly during executive functions tasks than untrained peers.
  • Gogulski, Juha; Zetter, Rasmus; Nyrhinen, Mikko; Pertovaara, Antti; Carlson, Synnove (2017)
    The human prefrontal cortex (PFC) has been shown to be important for metacognition, the capacity to monitor and control one's own cognitive processes. Here we dissected the neural architecture of somatosensory metacognition using navigated single-pulse transcranial magnetic stimulation (TMS) to modulate tactile working memory (WM) processing. We asked subjects to perform tactile WM tasks and to give a confidence rating for their performance after each trial. We circumvented the challenge of interindividual variability in functional brain anatomy by applying TMS to two PFC areas that, according to tractography, were neurally connected with the primary somatosensory cortex (S1): one area in the superior frontal gyrus (SFG), another in the middle frontal gyrus (MFG). These two PFC locations and a control cortical area were stimulated during both spatial and temporal tactile WM tasks. We found that tractography-guided TMS of the SFG area selectively enhanced metacognitive accuracy of tactile temporal, but not spatial WM. Stimulation of the MFG area that was also neurally connected with the S1 had no such effect on metacognitive accuracy of either the temporal or spatial tactile WM. Our findings provide causal evidence that the PFC contains distinct neuroanatomical substrates for introspective accuracy of tactile WM.
  • Carceller, Hector; Rovira-Esteban, Laura; Nacher, Juan; Castrén, Eero; Guirado, Ramon (2016)
    Reelin, a glycoprotein expressed by Cajal-Retzius neurons throughout the marginal layer of developing neocortex, has been extensively shown to play an important role during brain development, guiding neuronal migration and detachment from radial glia. During the adult life, however, many studies have associated Reelin expression to enhanced neuronal plasticity. Although its mechanism of action in the adult brain remains mostly unknown, Reelin is expressed mainly by a subset of mature interneurons. Here, we confirm the described phenotype of this subpopulation in the adult neocortex. We show that these mature interneurons, although being in close proximity, lack polysialylated neural cell adhesion molecule (PSA-NCAM) expression, a molecule expressed by a subpopulation of mature interneurons, related to brain development and involved in neuronal plasticity of the adult brain as well. However, in the layer II of Piriform cortex there is a high density of cells expressing Reelin whose neurochemical phenotype and connectivity has not been described before. Interestingly, in close proximity to these Reelin expressing cells there is a numerous subpopulation of immature neurons expressing PSA-NCAM and doublecortin (DCX) in this layer of the Piriform cortex. Here, we show that Reelin cells express the neuronal marker Neuronal Nuclei (NeuN), but however the majority of neurons lack markers of mature excitatory or inhibitory neurons. A detail analysis of its morphology indicates these that some of these cells might correspond to semilunar neurons. Interestingly, we found that the majority of these cells express T-box brain 1 (TBR-1) a transcription factor found not only in post-mitotic neurons that differentiate to glutamatergic excitatory neurons but also in Cajal-Retzius cells. We suggest that the function of these Reelin expressing cells might be similar to that of the Cajal-Retzius cells during development, having a role in the maintenance of the immature phenotype of the PSA-NCAM/DCX neurons through its receptors apolipoprotein E receptor 2 (ApoER2) and very low density lipoprotein receptor (VLDLR) in the Piriform cortex layer II during adulthood.
  • Petkoski, Spase; Palva, J. Matias; Jirsa, Viktor K. (2018)
    Architecture of phase relationships among neural oscillations is central for their functional significance but has remained theoretically poorly understood. We use phenomenological model of delay-coupled oscillators with increasing degree of topological complexity to identify underlying principles by which the spatio-temporal structure of the brain governs the phase lags between oscillatory activity at distant regions. Phase relations and their regions of stability are derived and numerically confirmed for two oscillators and for networks with randomly distributed or clustered bimodal delays, as a first approximation for the brain structural connectivity. Besides in-phase, clustered delays can induce anti-phase synchronization for certain frequencies, while the sign of the lags is determined by the natural frequencies and by the inhomogeneous network interactions. For in-phase synchronization faster oscillators always phase lead, while stronger connected nodes lag behind the weaker during frequency depression, which consistently arises for in-silico results. If nodes are in antiphase regime, then a distance Pi is added to the in-phase trends. The statistics of the phases is calculated from the phase locking values (PLV), as in many empirical studies, and we scrutinize the method's impact. The choice of surrogates do not affects the mean of the observed phase lags, but higher significance levels that are generated by some surrogates, cause decreased variance and might fail to detect the generally weaker coherence of the interhemispheric links. These links are also affected by the non-stationary and intermittent synchronization, which causes multimodal phase lags that can be misleading if averaged. Taken together, the results describe quantitatively the impact of the spatio-temporal connectivity of the brain to the synchronization patterns between brain regions, and to uncover mechanisms through which the spatio-temporal structure of the brain renders phases to be distributed around 0 and Pi.
  • Louhivuori, Lauri M.; Turunen, Pauli M.; Louhivuori, Verna; Yellapragada, Venkatram; Nordstrom, Tommy; Uhlen, Per; Akerman, Karl E. (2018)
    Radial glial cells play an essential role through their function as guides for neuronal migration during development. Disruption of metabotropic glutamate receptor 5 (mGluR5) function retards the growth of radial glial processes in vitro. Neuregulins (NRG) are activated by proteolytic cleavage and regulate (radial) glial maintenance via ErbB3/ErbB4 receptors. We show here that blocking ErbB4 disrupts radial process extension. Soluble NRG acting on ErbB4 receptors is able to promote radial process extension in particular where process elongation has been impeded by blockade of mGluR5, the nonselective cation channel canonical transient receptor potential 3 (TRPC3), or matrix metalloproteases (MMP). NRG does not restore retarded process growth caused by ErbB4 blockade. Stimulation of muscarinic receptors restores process elongation due to mGluR5 blockade but not that caused by TRPC3, MMP or ErbB4 blockade suggesting that muscarinic receptors can replace mGluR5 with respect to radial process extension. Additionally, NRG/ErbB4 causes Ca2+ mobilization in a population of cells through cooperation with ErbB1 receptors. Our results indicate that mGluR5 promotes radial process growth via NRG activation by a mechanism involving TRPC3 channels and MMPs. Thus neurotransmitters acting on G-protein coupled receptors could play a central role in the maintenance of the radial glial scaffold through activation of NRG/ErbB4 signaling.
  • Parmentier, Regis; Zhao, Yan; Perier, Magali; Akaoka, Hideo; Lintunen, Minnamaija; Hou, Yiping; Panula, Pertti; Watanabe, Takeshi; Franco, Patricia; Lin, Jian-Sheng (2016)
    Using knockout (KO) mice lacking the histamine (HA)-synthesizing enzyme (histidine decarboxylase, HDC), we have previously shown the importance of histaminergic neurons in maintaining wakefulness (W) under behavioral challenges. Since the central actions of HA are mediated by several receptor subtypes, it remains to be determined which one(s) could be responsible for such a role. We have therefore compared the cortical-EEG, sleep and W under baseline conditions or behavioral/pharmacological stimuli in littermate wild-type (WT) and H1-receptor KO (H1-/-) mice. We found that H1-/- mice shared several characteristics with HDC KO mice, i.e. 1) a decrease in W after lights-off despite its normal baseline daily amount; 2) a decreased EEG slow wave sleep (SWS)/W power ratio; 3) inability to maintain W in response to behavioral challenges demonstrated by a decreased sleep latency when facing various stimuli. These effects were mediated by central H1-receptors. Indeed, in WT mice, injection of triprolidine, a brain-penetrating H1-receptor antagonist increased SWS, whereas ciproxifan (H3-receptor antagonist/inverse agonist) elicited W; all these injections had no effect in H1-/- mice. Finally, H1-/- mice showed markedly greater changes in EEG power (notably in the 0.8-5 Hz band) and sleep-wake cycle than in WT mice after application of a cholinergic antagonist or an indirect agonist, i.e., scopolamine or physostigmine. Hence, the role of HA in wake-promotion is largely ensured by H1-receptors. An upregulated cholinergic system may account for a quasi-normal daily amount of W in HDC or H1-receptor KO mice and likely constitutes a major compensatory mechanism when the brain is facing deficiency of an activating system. This article is part of the Special Issue entitled 'Histamine Receptors'. Copyright (C) 2015 Elsevier Ltd. All rights reserved.
  • Guzelsoy, Gizem; Akkaya, Cansu; Atak, Dila; Dunn, Cory D.; Kabakcioglu, Alkan; Ozlu, Nurhan; Ince-Dunn, Gulayse (2019)
    Excitatory neurons of the mammalian cerebral cortex are organized into six functional layers characterized by unique patterns of connectivity, as well as distinctive physiological and morphological properties. Cortical layers appear after a highly regulated migration process in which cells move from the deeper, proliferative zone toward the superficial layers. Importantly, defects in this radial migration process have been implicated in neurodevelopmental and psychiatric diseases. Here we report that during the final stages of migration, transcription factor Neurogenic Differentiation 2 (Neurod2) contributes to terminal cellular localization within the cortical plate. In mice, in utero knockdown of Neurod2 resulted in reduced numbers of neurons localized to the uppermost region of the developing cortex, also termed the primitive cortical zone. Our ChIP-Seq and RNA-Seq analyses of genes regulated by NEUROD2 in the developing cortex identified a number of key target genes with known roles in Reelin signaling, a critical regulator of neuronal migration. Our focused analysis of regulation of the Reln gene, encoding the extracellular ligand REELIN, uncovered NEUROD2 binding to conserved E-box elements in multiple introns. Furthermore, we demonstrate that knockdown of NEUROD2 in primary cortical neurons resulted in a strong increase in Reln gene expression at the mRNA level, as well as a slight upregulation at the protein level. These data reveal a new role for NEUROD2 during the late stages of neuronal migration, and our analysis of its genomic targets offers new genes with potential roles in cortical lamination.
  • Ziermans, T.; Dumontheil, I.; Roggeman, C.; Peyrard-Janvid, M.; Matsson, H.; Kere, J.; Klingberg, T. (2012)