Umeå University's logo

umu.sePublications
Change search
Refine search result
1 - 23 of 23
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1. Bartoletti, Alessandro
    et al.
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Berardi, Nicoletta
    Maffei, Lamberto
    Environmental enrichment prevents effects of dark-rearing in the rat visual cortex2004In: Nature Neuroscience, ISSN 1097-6256, E-ISSN 1546-1726, Vol. 7, no 3, p. 215-216Article in journal (Refereed)
    Abstract [en]

    Environmental enrichment potentiates neural plasticity, enhancing acquisition and consolidation of memory traces. In the sensory cortices, after cortical circuit maturation and sensory function acquisition are completed, neural plasticity declines and the critical period 'closes'. In the visual cortex, this process can be prevented by dark-rearing, and here we show that environmental enrichment can promote physiological maturation and consolidation of visual cortical connections in dark-reared rats, leading to critical period closure.

  • 2. Blau, Axel
    et al.
    Murr, Angelika
    Wolff, Sandra
    Sernagor, Evelyne
    Medini, Paolo
    Iurilli, Giuliano
    Ziegler, Christiane
    Benfenati, Fabio
    Flexible, all-polymer microelectrode arrays for the capture of cardiac and neuronal signals2011In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 32, no 7, p. 1778-1786Article in journal (Refereed)
    Abstract [en]

    Microelectrode electrophysiology has become a widespread technique for the extracellular recording of bioelectrical signals. To date, electrodes are made of metals or inorganic semiconductors, or hybrids thereof. We demonstrate that these traditional conductors can be completely substituted by highly flexible electroconductive polymers. Pursuing a two-level replica-forming strategy, conductive areas for electrodes, leads and contact pads are defined as microchannels in poly(dimethylsiloxane) (PDMS) as a plastic carrier and track insulation material. These channels are coated by films of organic conductors such as polystyrenesulfonate-doped poly(3,4-ethylenedioxy-thiophene) (PEDOT:PSS) or filled with a graphite-PDMS (gPDMS) composite, either alone or in combination. The bendable, somewhat stretchable, non-cytotoxic and biostable all-polymer microelectrode arrays (polyMEAs) with a thickness below 500 μm and up to 60 electrodes reliably capture action potentials (APs) and local field potentials (LFPs) from acute preparations of heart muscle cells and retinal whole mounts, in vivo epicortical and epidural recordings as well as during long-term in vitro recordings from cortico-hippocampal co-cultures.

  • 3. Iurilli, Giuliano
    et al.
    Benfenati, Fabio
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Loss of Visually Driven Synaptic Responses in Layer 4 Regular-Spiking Neurons of Rat Visual Cortex in Absence of Competing Inputs2012In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 22, no 9, p. 2171-2181Article in journal (Refereed)
    Abstract [en]

    Monocular deprivation (MD) during development shifts the ocular preference of primary visual cortex (V1) neurons by depressing closed-eye responses and potentiating open-eye responses. As these 2 processes are temporally and mechanistically distinct, we tested whether loss of responsiveness occurs also in absence of competing inputs. We thus compared the effects of long-term MD in layer 4 regular-spiking pyramidal neurons (L4Ns) of binocular and monocular V1 (bV1 and mV1) with whole-cell recordings. In bV1, input depression was larger than potentiation, and the ocular dominance shift was larger for spike outputs. MD-but not retinal inactivation with tetrodotoxin-caused a comparable loss of synaptic and spike responsiveness in mV1, which is innervated only by the deprived eye. Conversely, brief MD depressed synaptic responses only in bV1. MD-driven depression in mV1 was accompanied by a proportional reduction of visual thalamic inputs, as assessed upon pharmacological silencing of intracortical transmission. Finally, sub- and suprathreshold responsiveness was similarly degraded in L4Ns of bV1 upon complete deprivation of patterned vision through a binocular deprivation period of comparable length. Thus, loss of synaptic inputs from the deprived eye occurs also in absence of competition in the main thalamorecipient lamina, albeit at a slower pace.

  • 4. Iurilli, Giuliano
    et al.
    Ghezzi, Diego
    Olcese, Umberto
    Lassi, Glenda
    Nazzaro, Cristiano
    Tonini, Raffaella
    Tucci, Valter
    Benfenati, Fabio
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Sound-Driven Synaptic Inhibition in Primary Visual Cortex2012In: Neuron, ISSN 0896-6273, E-ISSN 1097-4199, Vol. 73, no 4, p. 814-28Article in journal (Refereed)
    Abstract [en]

    Multimodal objects and events activate many sensory cortical areas simultaneously. This is possibly reflected in reciprocal modulations of neuronal activity, even at the level of primary cortical areas. However, the synaptic character of these interareal interactions, and their impact on synaptic and behavioral sensory responses are unclear. Here, we found that activation of auditory cortex by a noise burst drove local GABAergic inhibition on supragranular pyramids of the mouse primary visual cortex, via cortico-cortical connections. This inhibition was generated by sound-driven excitation of a limited number of cells in infragranular visual cortical neurons. Consequently, visually driven synaptic and spike responses were reduced upon bimodal stimulation. Also, acoustic stimulation suppressed conditioned behavioral responses to a dim flash, an effect that was prevented by acute blockade of GABAergic transmission in visual cortex. Thus, auditory cortex activation by salient stimuli degrades potentially distracting sensory processing in visual cortex by recruiting local, translaminar, inhibitory circuits.

  • 5.
    Iurilli, Giuliano
    et al.
    Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.
    Olcese, Umberto
    Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.
    Medini, Paolo
    Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.
    Preserved Excitatory-Inhibitory Balance of Cortical Synaptic Inputs following Deprived Eye Stimulation after a Saturating Period of Monocular Deprivation in Rats2013In: PloS one, ISSN 1932-6203, Vol. 8, no 12, p. e82044-Article in journal (Refereed)
    Abstract [en]

    Monocular deprivation (MD) during development leads to a dramatic loss of responsiveness through the deprived eye in primary visual cortical neurons, and to degraded spatial vision (amblyopia) in all species tested so far, including rodents. Such loss of responsiveness is accompanied since the beginning by a decreased excitatory drive from the thalamo-cortical inputs. However, in the thalamorecipient layer 4, inhibitory interneurons are initially unaffected by MD and their synapses onto pyramidal cells potentiate. It remains controversial whether ocular dominance plasticity similarly or differentially affects the excitatory and inhibitory synaptic conductances driven by visual stimulation of the deprived eye and impinging onto visual cortical pyramids, after a saturating period of MD. To address this issue, we isolated visually-driven excitatory and inhibitory conductances by in vivo whole-cell recordings from layer 4 regular-spiking neurons in the primary visual cortex (V1) of juvenile rats. We found that a saturating period of MD comparably reduced visually-driven excitatory and inhibitory conductances driven by visual stimulation of the deprived eye. Also, the excitatory and inhibitory conductances underlying the synaptic responses driven by the ipsilateral, left open eye were similarly potentiated compared to controls. Multiunit recordings in layer 4 followed by spike sorting indicated that the suprathreshold loss of responsiveness and the MD-driven ocular preference shifts were similar for narrow spiking, putative inhibitory neurons and broad spiking, putative excitatory neurons. Thus, by the time the plastic response has reached a plateau, inhibitory circuits adjust to preserve the normal balance between excitation and inhibition in the cortical network of the main thalamorecipient layer.

    Download full text (pdf)
    fulltext
  • 6.
    Jamroskovic, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Doimo, Mara
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Chand, Karam
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Obi, Ikenna
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Kumar, Rajendra
    Umeå University, Faculty of Science and Technology, Department of Physics. Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Brännström, Kristoffer
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Hedenström, Mattias
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Das, Rabindra Nath
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Akhunzianov, Almaz
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420008, Russia.
    Deiana, Marco
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Kasho, Kazutoshi
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Sulis Sato, Sebastian
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Pourbozorgi-Langroudi, Parham
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Mason, James E.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Öhlund, Daniel
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wanrooij, Sjoerd
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Chorell, Erik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sabouri, Nasim
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Quinazoline Ligands Induce Cancer Cell Death through Selective STAT3 Inhibition and G-Quadruplex Stabilization2020In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 142, no 6, p. 2876-2888Article in journal (Refereed)
    Abstract [en]

    The signal transducer and activator of transcription 3 (STAT3) protein is a master regulator of most key hallmarks and enablers of cancer, including cell proliferation and the response to DNA damage. G-Quadruplex (G4) structures are four-stranded noncanonical DNA structures enriched at telomeres and oncogenes' promoters. In cancer cells, stabilization of G4 DNAs leads to replication stress and DNA damage accumulation and is therefore considered a promising target for oncotherapy. Here, we designed and synthesized novel quinazoline-based compounds that simultaneously and selectively affect these two well-recognized cancer targets, G4 DNA structures and the STAT3 protein. Using a combination of in vitro assays, NMR, and molecular dynamics simulations, we show that these small, uncharged compounds not only bind to the STAT3 protein but also stabilize G4 structures. In human cultured cells, the compounds inhibit phosphorylation-dependent activation of STAT3 without affecting the antiapoptotic factor STAT1 and cause increased formation of G4 structures, as revealed by the use of a G4 DNA-specific antibody. As a result, treated cells show slower DNA replication, DNA damage checkpoint activation, and an increased apoptotic rate. Importantly, cancer cells are more sensitive to these molecules compared to noncancerous cell lines. This is the first report of a promising class of compounds that not only targets the DNA damage cancer response machinery but also simultaneously inhibits the STAT3-induced cancer cell proliferation, demonstrating a novel approach in cancer therapy.

    Download full text (pdf)
    fulltext
  • 7.
    Kokinovic, Bojana
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. epartment of Neuroscience and Brain Technologies (NBT), Italian Institute of Technology (IIT), Genova, Italy.
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Loss of GABAB-mediated interhemispheric synaptic inhibition in stroke periphery2018In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 596, no 10, p. 1949-1964Article in journal (Refereed)
    Abstract [en]

    Recovery after stroke is mediated by plastic changes largely occurring in the lesion periphery. However, little is known about the microcircuit changes underlying recovery, the extent to which perilesional plasticity occurs at synaptic input vs. spike output level, and the connectivity behind such synaptic plasticity. We combined intrinsic imaging with extracellular and intracellular recordings and pharmacological inactivation in a focal stroke in mouse somatosensory cortex (S1). In vivo whole-cell recordings in hindlimb S1 (hS1) showed synaptic responses also to forelimb stimulation in controls, and such responses were abolished by stroke in the neighbouring forelimb area (fS1), suggesting that, under normal conditions, they originate via horizontal connections from the neighbouring fS1. Synaptic and spike responses to forelimb stimulation in hS1 recovered to quasi-normal levels 2weeks after stroke, without changes in intrinsic excitability and hindlimb-evoked spike responses. Recovered synaptic responses had longer latencies, suggesting a long-range origin of the recovery, prompting us to investigate the role of callosal inputs in the recovery process. Contralesional S1 silencing unmasked significantly larger responses to both limbs in controls, a phenomenon that was not observed when GABAB receptors were antagonized in the recorded area. Conversely, such GABAB-mediated interhemispheric inhibition was not detectable after stroke: callosal input silencing failed to change hindlimb responses, whereas it robustly reduced recovered forelimb responses. Thus, recovery of subthreshold responsiveness in the stroke periphery is accompanied by a loss of interhemispheric inhibition and this is a result of pathway-specific facilitatory action on the affected sensory response from the contralateral cortex.

  • 8.
    Kuznetsova, Tatiana
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Antos, Kamil
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Malinina, Evgenya
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Papaioannou, Stylianos
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Visual stimulation with blue wavelength light drives V1 effectively eliminating stray light contamination during two-photon calcium imaging2021In: Journal of Neuroscience Methods, ISSN 0165-0270, E-ISSN 1872-678X, Vol. 362, article id 109287Article in journal (Refereed)
    Abstract [en]

    Background: Brain visual circuits are often studied in vivo by imaging Ca2+ indicators with green-shifted emission spectra. Polychromatic white visual stimuli have a spectrum that partially overlaps indicators´ emission spectra, resulting in significant contamination of calcium signals.

    New method: To overcome light contamination problems we choose blue visual stimuli, having a spectral composition not overlapping with Ca2+ indicator´s emission spectrum. To compare visual responsiveness to blue and white stimuli we used electrophysiology (visual evoked potentials –VEPs) and 3D acousto-optic two-photon (2P) population Ca2+ imaging in mouse primary visual cortex (V1).

    Results: VEPs in response to blue and white stimuli had comparable peak amplitudes and latencies. Ca2+ imaging in a Thy1 GP4.3 line revealed that the populations of neurons responding to blue and white stimuli were largely overlapping, that their responses had similar amplitudes, and that functional response properties such as orientation and direction selectivities were also comparable.

    Comparison with existing methods: Masking or shielding the microscope are often used to minimize the contamination of Ca2+ signal by white light, but they are time consuming, bulky and thus can limit experimental design, particularly in the more and more frequently used awake set-up. Blue stimuli not interfering with imaging allow to omit shielding.

    Conclusions: Together, our results show that the selected blue light stimuli evoke responses comparable to those evoked by white stimuli in mouse V1. This will make complex designs of imaging experiments in behavioral set-ups easier, and facilitate the combination of Ca2+ imaging with electrophysiology and optogenetics.

    Download full text (pdf)
    fulltext
  • 9.
    Lorenzon, Paolo
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Antos, Kamil
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Tripathi, Anushree
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Vedin, Viktoria
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Berghard, Anna
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Estrus-specific synaptic inhibition of accessory olfactory bulb output neurons in response to vagino-cervical stimulationManuscript (preprint) (Other academic)
    Abstract [en]

    This is the first study of the electrophysiological response of accessory olfactory bulb (AOB) output neurons to vagino-cervical stimulation by in vivo whole-cell recordings, allowing for measurements at synaptic input and spike output level in identified microcircuit cell types in naturally cycling mice. AOB is relaying specialized odorous information and e.g. shows plasticity essential for formation of a vomeronasal organ (VNO)-pheromonal memory of the mating male. Thus, not only VNO-pheromonal information, but also representation of coital somatosensory information needs to reach AOB. AOB in vivo responses to VNO-pheromones does not correlate in time to stimulus. We find that vagino-cervical stimuli evoke a stimulus-locked response in AOB regardless if the female is in estrus or not, and the response is sensitive to noradrenergic α1-adrenergic receptor blockade. By retrograde labeling we confirm that norepinephrine-producing locus coeruleus neurons innervate the AOB and functional anatomy demonstrated that vagino-cervical information reaches locus coeruleus in both estrus and diestrus. The spontaneous activity of mitral-tufted output neurons show propensity to fire bursts of spikes specifically during estrus suggesting state-dependent excitability of the network. Intriguingly, only during estrus do the output neurons show norepinephrine-dependent, dendro-dendritic inhibition of spike output during vagino-cervical stimulation, which is accompanied by longer activation of inhibitory granule cell layer of AOB. Thus, the estrous state of the circuit appears required for coital stimulation to evoke synaptic inhibition in main output neurons of the microcircuit, which may contribute to formation of memory of the mating male, possibly via burst-dependent increase of dendro-dendritic inhibition

  • 10.
    Lorenzon, Paolo
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Antos, Kamil
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Tripathi, Anushree
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Vedin, Viktoria
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Berghard, Anna
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    In vivo spontaneous activity and coital-evoked inhibition of mouse accessory olfactory bulb output neurons2023In: iScience, E-ISSN 2589-0042 , Vol. 26, no 9, article id 107545Article in journal (Refereed)
    Abstract [en]

    Little is known about estrous effects on brain microcircuits. We examined the accessory olfactory bulb (AOB) in vivo, in anesthetized naturally cycling females, as model microcircuit receiving coital somatosensory information. Whole-cell recordings demonstrate that output neurons are relatively hyperpolarized in estrus and unexpectedly fire high frequency bursts of action potentials. To mimic coitus, a calibrated artificial vagino-cervical stimulation (aVCS) protocol was devised. aVCS evoked stimulus-locked local field responses in the interneuron layer independent of estrous stage. The response is sensitive to α1-adrenergic receptor blockade, as expected since aVCS increases norepinephrine release in AOB. Intriguingly, only in estrus does aVCS inhibit AOB spike output. Estrus-specific output reduction coincides with prolonged aVCS activation of inhibitory interneurons. Accordingly, in estrus the AOB microcircuit sets the stage for coital stimulation to inhibit the output neurons, possibly via high frequency bursting-dependent enhancement of reciprocal synapse efficacy between inter- and output neurons.

    Download full text (pdf)
    fulltext
  • 11. Mazzaro, Nadia
    et al.
    Barini, Erica
    Spillantini, Maria Grazia
    Goedert, Michel
    Medini, Paolo
    Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.
    Gasparini, Laura
    Tau-driven neuronal and neurotrophic dysfunction in a mouse model of early tauopathy2016In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 36, no 7, p. 2086-2100Article in journal (Refereed)
    Abstract [en]

    Tauopathies are neurodegenerative diseases characterized by intraneuronal inclusions of hyperphosphorylated tau protein and abnormal expression of brain-derived neurotrophic factor (BDNF), a key modulator of neuronal survival and function. The severity of both these pathological hallmarks correlate with the degree of cognitive impairment in patients. However, how tau pathology specifically modifies BDNF signaling and affects neuronal function during early prodromal stages of tauopathy remains unclear. Here, we report that the mild tauopathy developing in retinal ganglion cells (RGCs) of the P301S tau transgenic (P301S) mouse induces functional retinal changes by disrupting BDNF signaling via the TrkB receptor. In adult P301S mice, the physiological visual response of RGCs to pattern light stimuli and retinal acuity decline significantly. As a consequence, the activity-dependent secretion of BDNF in the vitreous is impaired in P301S mice. Further, in P301S retinas, TrkB receptors are selectively upregulated, but uncoupled from downstream extracellular signal-regulated kinase (ERK) 1/2 signaling. We also show that the impairment of TrkB signaling is triggered by tau pathology and mediates the tau-induced dysfunction of visual response. Overall our results identify a neurotrophin-mediated mechanism by which tau induces neuronal dysfunction during prodromal stages of tauopathy and define tau-driven pathophysiological changes of potential value to support early diagnosis and informed therapeutic decisions.

    Download full text (pdf)
    fulltext
  • 12.
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Cell-type-specific sub- and suprathreshold receptive fields of layer 4 and layer 2/3 pyramids in rat primary visual cortex.2011In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 190, p. 112-26Article in journal (Refereed)
    Abstract [en]

    Connectivity of cortical pyramidal neurons is layer-specific in the primary visual cortex (V1) and this is thought to be reflected in different receptive field (RF) properties of layer 4 and layer 2/3 pyramidal neurons (L4Ps and L2/3Ps, respectively). However, it remains unclear how the two cell populations convert incoming visually driven synaptic inputs into action potential (AP) outputs. Here I compared postsynaptic potentials (PSPs) and AP responses of L4Ps and L2/3Ps in the binocular portion of rat V1 by intrinsic optical imaging (IOI)-targeted whole-cell recordings followed by anatomical identification and dendritic reconstructions. L2/3Ps had about 2-fold longer dendritic branches and a higher number of branch points and endings in their apical portions. Functionally, L2/3Ps had more hyperpolarized resting potentials and lower rates of spontaneous APs (medians: 0.07 vs. 0.60 AP/s). PSP responses to optimally oriented moving bars were comparable in terms of amplitude (16.0±0.9 vs. 17.3±1.1 mV for L2/3Ps and L4Ps, respectively), reliability and size of the RF. The modulated component of subthreshold responses of L4Ps to optimal sinusoidal drifting gratings was larger and their PSP onset latency in response to bars flashed in the cell's RF center were shorter (60 vs. 86 ms). In contrast to the similarities of PSP responses to moving bars, AP responses of L2/3Ps were more sparse (medians: 0.7 vs. 2.9 APs/stimulus passage), less reliable, but sharper in terms of angular size. Based on the differences of subthreshold inputs, I conclude that L4Ps may receive mostly thalamic inputs, whereas L2/3Ps may receive both thalamic and cortical inputs from layer 4. The comparable subthreshold responses to moving bars are converted by L2/3Ps into sparser but sharper AP outputs possibly by cell-type-specific AP-generating mechanisms or differences in visually driven inhibitory inputs.

  • 13.
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Experience-dependent plasticity of visual cortical microcircuits2014In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 278, p. 367-384Article, review/survey (Refereed)
    Abstract [en]

    The recent decade testified a tremendous increase in our knowledge on how cell-type-specific microcircuits process sensory information in the neocortex and on how such circuitry reacts to manipulations of the sensory environment. Experience-dependent plasticity has now been investigated with techniques endowed with cell resolution during both postnatal development and in adult animals. This review recapitulates the main recent findings in the field using mainly the primary visual cortex as a model system to highlight the more important questions and physiological principles (such as the role of non-competitive mechanisms, the role of inhibition in excitatory cell plasticity, the functional importance of spine and axonal plasticity on a microscale level). I will also discuss on which scientific problems the debate and controversies are more pronounced. New technologies that allow to perturbate cell-type-specific subcircuits will certainly shine new light in the years to come at least on some of the still open questions. (C) 2014 The Author. Published by Elsevier Ltd. on behalf of IBRO.

    Download full text (pdf)
    fulltext
  • 14.
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Layer- and Cell-Type-Specific Subthreshold and Suprathreshold Effects of Long-Term Monocular Deprivation in Rat Visual Cortex2011In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 31, no 47, p. 17134-17148Article in journal (Refereed)
    Abstract [en]

    Connectivity and dendritic properties are determinants of plasticity that are layer and cell-type specific in the neocortex. However, the impact of experience-dependent plasticity at the level of synaptic inputs and spike outputs remains unclear along vertical cortical microcircuits. Here I compared subthreshold and suprathreshold sensitivity to prolonged monocular deprivation (MD) in rat binocular visual cortex in layer 4 and layer 2/3 pyramids (4Ps and 2/3Ps) and in thick-tufted and nontufted layer 5 pyramids (5TPs and 5NPs), which innervate different extracortical targets. In normal rats, 5TPs and 2/3Ps are the most binocular in terms of synaptic inputs, and 5NPs are the least. Spike responses of all 5TPs were highly binocular, whereas those of 2/3Ps were dominated by either the contralateral or ipsilateral eye. MD dramatically shifted the ocular preference of 2/3Ps and 4Ps, mostly by depressing deprived-eye inputs. Plasticity was profoundly different in layer 5. The subthreshold ocular preference shift was sevenfold smaller in 5TPs because of smaller depression of deprived inputs combined with a generalized loss of responsiveness, and was undetectable in 5NPs. Despite their modest ocular dominance change, spike responses of 5TPs consistently lost their typically high binocularity during MD. The comparison of MD effects on 2/3Ps and 5TPs, the main affected output cells of vertical microcircuits, indicated that subthreshold plasticity is not uniquely determined by the initial degree of input binocularity. The data raise the question of whether 5TPs are driven solely by 2/3Ps during MD. The different suprathreshold plasticity of the two cell populations could underlie distinct functional deficits in amblyopia.

  • 15.
    Medini, Paolo
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Pizzorusso, Tommaso
    Visual experience and plasticity of the visual cortex: a role for epigenetic mechanisms2008In: Frontiers in bioscience : a journal and virtual library, ISSN 1093-4715, Vol. 13, p. 3000-3007Article in journal (Refereed)
    Abstract [en]

    Plasticity of cortical circuits is maximal during critical periods of postnatal development. Ocular dominance plasticity is a classical model to understand the role of experience in development of the visual cortex. Recent studies are beginning to unravel the synaptic mechanisms underlying this form of plasticity and to elucidate the different plasticity of juvenile and adult animals at mechanistic and molecular level. These investigations indicate that this form of plasticity is regulated by factors located at extracellular and intracellular level. The molecular composition of the extracellular environment in which synaptic plasticity occurs changes during development becoming less permissive for plasticity. In addition, visual experience activates epigenetic mechanisms of regulation of gene transcription that becomes downregulated in adult animals.

  • 16. Olcese, Umberto
    et al.
    Iurilli, Giuliano
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Cellular and synaptic architecture of multisensory integration in the mouse neocortex2013In: Neuron, ISSN 0896-6273, E-ISSN 1097-4199, Vol. 79, no 3, p. 579-593Article in journal (Refereed)
    Abstract [en]

    Multisensory integration (MI) is crucial for sensory processing, but it is unclear how MI is organized in cortical microcircuits. Whole-cell recordings in a mouse visuotactile area located between primary visual and somatosensory cortices revealed that spike responses were less bimodal than synaptic responses but displayed larger multisensory enhancement. MI was layer and cell type specific, with multisensory enhancement being rare in the major class of inhibitory interneurons and in the output infragranular layers. Optogenetic manipulation of parvalbumin-positive interneuron activity revealed that the scarce MI of interneurons enables MI in neighboring pyramids. Finally, single-cell resolution calcium imaging revealed a gradual merging of modalities: unisensory neurons had higher densities toward the borders of the primary cortices, but were located in unimodal clusters in the middle of the cortical area. These findings reveal the role of different neuronal subcircuits in the synaptic process of MI in the rodent parietal cortex.

  • 17.
    Papaioannou, Stylianos
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Advantages, Pitfalls, and Developments of All Optical Interrogation Strategies of Microcircuits in vivo2022In: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 16, article id 859803Article, review/survey (Refereed)
    Abstract [en]

    The holy grail for every neurophysiologist is to conclude a causal relationship between an elementary behaviour and the function of a specific brain area or circuit. Our effort to map elementary behaviours to specific brain loci and to further manipulate neural activity while observing the alterations in behaviour is in essence the goal for neuroscientists. Recent advancements in the area of experimental brain imaging in the form of longer wavelength near infrared (NIR) pulsed lasers with the development of highly efficient optogenetic actuators and reporters of neural activity, has endowed us with unprecedented resolution in spatiotemporal precision both in imaging neural activity as well as manipulating it with multiphoton microscopy. This readily available toolbox has introduced a so called all-optical physiology and interrogation of circuits and has opened new horizons when it comes to precisely, fast and non-invasively map and manipulate anatomically, molecularly or functionally identified mesoscopic brain circuits. The purpose of this review is to describe the advantages and possible pitfalls of all-optical approaches in system neuroscience, where by all-optical we mean use of multiphoton microscopy to image the functional response of neuron(s) in the network so to attain flexible choice of the cells to be also optogenetically photostimulated by holography, in absence of electrophysiology. Spatio-temporal constraints will be compared toward the classical reference of electrophysiology methods. When appropriate, in relation to current limitations of current optical approaches, we will make reference to latest works aimed to overcome these limitations, in order to highlight the most recent developments. We will also provide examples of types of experiments uniquely approachable all-optically. Finally, although mechanically non-invasive, all-optical electrophysiology exhibits potential off-target effects which can ambiguate and complicate the interpretation of the results. In summary, this review is an effort to exemplify how an all-optical experiment can be designed, conducted and interpreted from the point of view of the integrative neurophysiologist.

    Download full text (pdf)
    fulltext
  • 18.
    Papaioannou, Stylianos
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Current state-of-the-art and future perspectives of all-optical interrogation strategies of brain microcircuits in vivo: the perspective of integrative neurophysiologistsManuscript (preprint) (Other academic)
  • 19. Pizzorusso, Tommaso
    et al.
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Berardi, Nicoletta
    Chierzi, Sabrina
    Fawcett, James W
    Maffei, Lamberto
    Reactivation of ocular dominance plasticity in the adult visual cortex2002In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 298, no 5596, p. 1248-51Article in journal (Refereed)
    Abstract [en]

    In young animals, monocular deprivation leads to an ocular dominance shift, whereas in adults after the critical period there is no such shift. Chondroitin sulphate proteoglycans (CSPGs) are components of the extracellular matrix (ECM) inhibitory for axonal sprouting. We tested whether the developmental maturation of the ECM is inhibitory for experience-dependent plasticity in the visual cortex. The organization of CSPGs into perineuronal nets coincided with the end of the critical period and was delayed by dark rearing. After CSPG degradation with chondroitinase-ABC in adult rats, monocular deprivation caused an ocular dominance shift toward the nondeprived eye. The mature ECM is thus inhibitory for experience-dependent plasticity, and degradation of CSPGs reactivates cortical plasticity.

  • 20. Pizzorusso, Tommaso
    et al.
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Landi, Silvia
    Baldini, Sara
    Berardi, Nicoletta
    Maffei, Lamberto
    Structural and functional recovery from early monocular deprivation in adult rats2006In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 103, no 22, p. 8517-8522Article in journal (Refereed)
    Abstract [en]

    Visual deficits caused by abnormal visual experience during development are hard to recover in adult animals. Removal of chondroitin sulfate proteoglycans from the mature extracellular matrix with chondroitinase ABC promotes plasticity in the adult visual cortex. We tested whether chondroitinase ABC treatment of adult rats facilitates anatomical, functional, and behavioral recovery from the effects of a period of monocular deprivation initiated during the critical period for monocular deprivation. We found that chondroitinase ABC treatment coupled with reverse lid-suturing causes a complete recovery of ocular dominance, visual acuity, and dendritic spine density in adult rats. Thus, manipulations of the extracellular matrix can be used to promote functional recovery in the adult cortex.

  • 21. Sale, Alessandro
    et al.
    Maya Vetencourt, José Fernando
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Cenni, Maria Cristina
    Baroncelli, Laura
    De Pasquale, Roberto
    Maffei, Lamberto
    Environmental enrichment in adulthood promotes amblyopia recovery through a reduction of intracortical inhibition2007In: Nature Neuroscience, ISSN 1097-6256, E-ISSN 1546-1726, Vol. 10, no 6, p. 679-681Article in journal (Refereed)
    Abstract [en]

    Loss of visual acuity caused by abnormal visual experience during development (amblyopia) is an untreatable pathology in adults. We report that environmental enrichment in adult amblyopic rats restored normal visual acuity and ocular dominance. These effects were due to reduced GABAergic inhibition in the visual cortex, accompanied by increased expression of BDNF and reduced density of extracellular-matrix perineuronal nets, and were prevented by enhancement of inhibition through benzodiazepine cortical infusion.

  • 22.
    Tran, Phong
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Wanrooij, Paulina H.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Lorenzon, Paolo
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Sharma, Sushma
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Thelander, Lars
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Nilsson, Anna Karin
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Olofsson, Anna-Karin
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    von Hofsten, Jonas
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Chabes, Andrei
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    De novo dNTP production is essential for normal postnatal murine heart development2019In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 394, no 44, p. 15889-15897, article id jbc.RA119.009492Article in journal (Refereed)
    Abstract [en]

    The building blocks of DNA, dNTPs, can be produced de novo or can be salvaged from deoxyribonucleosides. However, to what extent the absence of de novo dNTP production can be compensated for by the salvage pathway is unknown. Here, we eliminated de novo dNTP synthesis in the mouse heart and skeletal muscle by inactivating ribonucleotide reductase (RNR), a key enzyme for the de novo production of dNTPs, at embryonic day 13. All other tissues had normal de novo dNTP synthesis and theoretically could supply heart and skeletal muscle with deoxyribonucleosides needed for dNTP production by salvage. We observed that the dNTP and NTP pools in wild-type postnatal hearts are unexpectedly asymmetric, with unusually high dGTP and GTP levels compared with those in whole mouse embryos or murine cell cultures. We found that RNR inactivation in heart led to strongly decreased dGTP and increased dCTP, dTTP, and dATP pools; aberrant DNA replication; defective expression of muscle-specific proteins; progressive heart abnormalities; disturbance of the cardiac conduction system; and lethality between the second and fourth weeks after birth. We conclude that dNTP salvage cannot substitute for de novo dNTP synthesis in the heart and that cardiomyocytes and myocytes initiate DNA replication despite an inadequate dNTP supply. We discuss the possible reasons for the observed asymmetry in dNTP and NTP pools in wildtype hearts.

  • 23.
    Tripathi, Anushree
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Sulis Sato, Sebastian
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Cortico-cortical connectivity behind acoustic information transfer to mouse orbitofrontal cortex is sensitive to neuromodulation and displays local sensory gating: relevance in disorders with auditory hallucinations?2021In: Journal of Psychiatry & Neuroscience, ISSN 1180-4882, E-ISSN 1488-2434, Vol. 46, no 3, p. E371-E387Article in journal (Refereed)
    Abstract [en]

    Background: Auditory hallucinations (which occur when the distinction between thoughts and perceptions is blurred) are common in psychotic disorders. The orbitofrontal cortex (OFC) may be implicated, because it receives multiple inputs, including sound and affective value via the amygdala, orchestrating complex emotional responses. We aimed to elucidate the circuit and neuromodulatory mechanisms that underlie the processing of emotionally salient auditory stimuli in the OFC — mechanisms that may be involved in auditory hallucinations. Methods: We identified the cortico-cortical connectivity conveying auditory information to the mouse OFC; its sensitivity to neuromodulators involved in psychosis and postpartum depression, such as dopamine and neurosteroids; and its sensitivity to sensory gating (defective in dysexecutive syndromes). Results: Retrograde tracers in OFC revealed input cells in all auditory cortices. Acoustic responses were abolished by pharmacological and chemogenetic inactivation of the above-identified pathway. Acoustic responses in the OFC were reduced by local dopaminergic agonists and neurosteroids. Noticeably, apomorphine action lasted longer in the OFC than in auditory areas, and its effect was modality-specific (augmentation for visual responses), whereas neurosteroid action was sex-specific. Finally, acoustic responses in the OFC reverberated to the auditory association cortex via feedback connections and displayed sensory gating, a phenomenon of local origin, given that it was not detectable in input auditory cortices. Limitations: Although our findings were for mice, connectivity and sensitivity to neuromodulation are conserved across mammals. Conclusion: The corticocortical loop from the auditory association cortex to the OFC is dramatically sensitive to dopamine and neurosteroids. This suggests a clinically testable circuit behind auditory hallucinations. The function of OFC input–output circuits can be studied in mice with targeted and clinically relevant mutations related to their response to emotionally salient sounds.

1 - 23 of 23
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf