---
_id: '9097'
abstract:
- lang: eng
  text: Psoriasis is a chronic inflammatory skin disease clinically characterized
    by the appearance of red colored, well-demarcated plaques with thickened skin
    and with silvery scales. Recent studies have established the involvement of a
    complex signalling network of interactions between cytokines, immune cells and
    skin cells called keratinocytes. Keratinocytes form the cells of the outermost
    layer of the skin (epidermis). Visible plaques in psoriasis are developed due
    to the fast proliferation and unusual differentiation of keratinocyte cells. Despite
    that, the exact mechanism of the appearance of these plaques in the cytokine-immune
    cell network is not clear. A mathematical model embodying interactions between
    key immune cells believed to be involved in psoriasis, keratinocytes and relevant
    cytokines has been developed. The complex network formed of these interactions
    poses several challenges. Here, we choose to study subnetworks of this complex
    network and initially focus on interactions involving TNFα, IL-23/IL-17, and IL-15.
    These are chosen based on known evidence of their therapeutic efficacy. In addition,
    we explore the role of IL-15 in the pathogenesis of psoriasis and its potential
    as a future drug target for a novel treatment option. We perform steady state
    analyses for these subnetworks and demonstrate that the interactions between cells,
    driven by cytokines could cause the emergence of a psoriasis state (hyper-proliferation
    of keratinocytes) when levels of TNFα, IL-23/IL-17 or IL-15 are increased. The
    model results explain and support the clinical potentiality of anti-cytokine treatments.
    Interestingly, our results suggest different dynamic scenarios underpin the pathogenesis
    of psoriasis, depending upon the dominant cytokines of subnetworks. We observed
    that the increase in the level of IL-23/IL-17 and IL-15 could lead to psoriasis
    via a bistable route, whereas an increase in the level of TNFα would lead to a
    monotonic and gradual disease progression. Further, we demonstrate how this insight,
    bistability, could be exploited to improve the current therapies and develop novel
    treatment strategies for psoriasis.
acknowledgement: RP acknowledges the Department of Science and Technology, India for
  the support through the DST-INSPIRE Faculty Award (DST/INSPIRE/04/2015/001939).
  This work was supported by the Engineering and Physical Sciences Research Council
  (EPSRC), United Kingdom (Grant numbers EP/J018295/1, EP/J018392/1, EP/N014391/1).
  The contribution of RP was also supported by the later Grant. This work was generously
  supported by the Welcome Trust Institutional Strategic Support Award (204909/Z/16/Z)
  too. The contribution of MG was supported by the EPSRC via EP/N014391/1 and a Wellcome
  Trust Institutional Strategic Support Award (WT105618MA). The contribution of YA
  was generously supported by the Wellcome Trust Institutional Strategic Support Award
  (WT105618MA).
article_number: '2204'
article_processing_charge: No
article_type: original
author:
- first_name: Rakesh
  full_name: Pandey, Rakesh
  last_name: Pandey
- first_name: Yusur
  full_name: Al-Nuaimi, Yusur
  last_name: Al-Nuaimi
- first_name: Rajiv Kumar
  full_name: Mishra, Rajiv Kumar
  id: 46CB58F2-F248-11E8-B48F-1D18A9856A87
  last_name: Mishra
- first_name: Sarah K.
  full_name: Spurgeon, Sarah K.
  last_name: Spurgeon
- first_name: Marc
  full_name: Goodfellow, Marc
  last_name: Goodfellow
citation:
  ama: Pandey R, Al-Nuaimi Y, Mishra RK, Spurgeon SK, Goodfellow M. Role of subnetworks
    mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis
    of psoriasis. <i>Scientific Reports</i>. 2021;11. doi:<a href="https://doi.org/10.1038/s41598-020-80507-7">10.1038/s41598-020-80507-7</a>
  apa: Pandey, R., Al-Nuaimi, Y., Mishra, R. K., Spurgeon, S. K., &#38; Goodfellow,
    M. (2021). Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network
    involved in the pathogenesis of psoriasis. <i>Scientific Reports</i>. Springer
    Nature. <a href="https://doi.org/10.1038/s41598-020-80507-7">https://doi.org/10.1038/s41598-020-80507-7</a>
  chicago: Pandey, Rakesh, Yusur Al-Nuaimi, Rajiv Kumar Mishra, Sarah K. Spurgeon,
    and Marc Goodfellow. “Role of Subnetworks Mediated by TNF α, IL-23/IL-17 and IL-15
    in a Network Involved in the Pathogenesis of Psoriasis.” <i>Scientific Reports</i>.
    Springer Nature, 2021. <a href="https://doi.org/10.1038/s41598-020-80507-7">https://doi.org/10.1038/s41598-020-80507-7</a>.
  ieee: R. Pandey, Y. Al-Nuaimi, R. K. Mishra, S. K. Spurgeon, and M. Goodfellow,
    “Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved
    in the pathogenesis of psoriasis,” <i>Scientific Reports</i>, vol. 11. Springer
    Nature, 2021.
  ista: Pandey R, Al-Nuaimi Y, Mishra RK, Spurgeon SK, Goodfellow M. 2021. Role of
    subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in
    the pathogenesis of psoriasis. Scientific Reports. 11, 2204.
  mla: Pandey, Rakesh, et al. “Role of Subnetworks Mediated by TNF α, IL-23/IL-17
    and IL-15 in a Network Involved in the Pathogenesis of Psoriasis.” <i>Scientific
    Reports</i>, vol. 11, 2204, Springer Nature, 2021, doi:<a href="https://doi.org/10.1038/s41598-020-80507-7">10.1038/s41598-020-80507-7</a>.
  short: R. Pandey, Y. Al-Nuaimi, R.K. Mishra, S.K. Spurgeon, M. Goodfellow, Scientific
    Reports 11 (2021).
date_created: 2021-02-07T23:01:12Z
date_published: 2021-01-26T00:00:00Z
date_updated: 2022-08-19T07:22:23Z
day: '26'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1038/s41598-020-80507-7
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publication: Scientific Reports
publication_identifier:
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publication_status: published
publisher: Springer Nature
quality_controlled: '1'
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title: Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved
  in the pathogenesis of psoriasis
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 11
year: '2021'
...
---
_id: '1432'
abstract:
- lang: eng
  text: CA3–CA3 recurrent excitatory synapses are thought to play a key role in memory
    storage and pattern completion. Whether the plasticity properties of these synapses
    are consistent with their proposed network functions remains unclear. Here, we
    examine the properties of spike timing-dependent plasticity (STDP) at CA3–CA3
    synapses. Low-frequency pairing of excitatory postsynaptic potentials (EPSPs)
    and action potentials (APs) induces long-term potentiation (LTP), independent
    of temporal order. The STDP curve is symmetric and broad (half-width ~150 ms).
    Consistent with these STDP induction properties, AP–EPSP sequences lead to supralinear
    summation of spine [Ca2+] transients. Furthermore, afterdepolarizations (ADPs)
    following APs efficiently propagate into dendrites of CA3 pyramidal neurons, and
    EPSPs summate with dendritic ADPs. In autoassociative network models, storage
    and recall are more robust with symmetric than with asymmetric STDP rules. Thus,
    a specialized STDP induction rule allows reliable storage and recall of information
    in the hippocampal CA3 network.
acknowledgement: 'We thank Jozsef Csicsvari and Nelson Spruston for critically reading
  the manuscript. We also thank A. Schlögl for programming, F. Marr for technical
  assistance and E. Kramberger for manuscript editing. '
article_number: '11552'
author:
- first_name: Rajiv Kumar
  full_name: Mishra, Rajiv Kumar
  id: 46CB58F2-F248-11E8-B48F-1D18A9856A87
  last_name: Mishra
- first_name: Sooyun
  full_name: Kim, Sooyun
  id: 394AB1C8-F248-11E8-B48F-1D18A9856A87
  last_name: Kim
- first_name: José
  full_name: Guzmán, José
  id: 30CC5506-F248-11E8-B48F-1D18A9856A87
  last_name: Guzmán
  orcid: 0000-0003-2209-5242
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
citation:
  ama: Mishra RK, Kim S, Guzmán J, Jonas PM. Symmetric spike timing-dependent plasticity
    at CA3–CA3 synapses optimizes storage and recall in autoassociative networks.
    <i>Nature Communications</i>. 2016;7. doi:<a href="https://doi.org/10.1038/ncomms11552">10.1038/ncomms11552</a>
  apa: Mishra, R. K., Kim, S., Guzmán, J., &#38; Jonas, P. M. (2016). Symmetric spike
    timing-dependent plasticity at CA3–CA3 synapses optimizes storage and recall in
    autoassociative networks. <i>Nature Communications</i>. Nature Publishing Group.
    <a href="https://doi.org/10.1038/ncomms11552">https://doi.org/10.1038/ncomms11552</a>
  chicago: Mishra, Rajiv Kumar, Sooyun Kim, José Guzmán, and Peter M Jonas. “Symmetric
    Spike Timing-Dependent Plasticity at CA3–CA3 Synapses Optimizes Storage and Recall
    in Autoassociative Networks.” <i>Nature Communications</i>. Nature Publishing
    Group, 2016. <a href="https://doi.org/10.1038/ncomms11552">https://doi.org/10.1038/ncomms11552</a>.
  ieee: R. K. Mishra, S. Kim, J. Guzmán, and P. M. Jonas, “Symmetric spike timing-dependent
    plasticity at CA3–CA3 synapses optimizes storage and recall in autoassociative
    networks,” <i>Nature Communications</i>, vol. 7. Nature Publishing Group, 2016.
  ista: Mishra RK, Kim S, Guzmán J, Jonas PM. 2016. Symmetric spike timing-dependent
    plasticity at CA3–CA3 synapses optimizes storage and recall in autoassociative
    networks. Nature Communications. 7, 11552.
  mla: Mishra, Rajiv Kumar, et al. “Symmetric Spike Timing-Dependent Plasticity at
    CA3–CA3 Synapses Optimizes Storage and Recall in Autoassociative Networks.” <i>Nature
    Communications</i>, vol. 7, 11552, Nature Publishing Group, 2016, doi:<a href="https://doi.org/10.1038/ncomms11552">10.1038/ncomms11552</a>.
  short: R.K. Mishra, S. Kim, J. Guzmán, P.M. Jonas, Nature Communications 7 (2016).
date_created: 2018-12-11T11:51:59Z
date_published: 2016-05-13T00:00:00Z
date_updated: 2023-09-07T11:55:25Z
day: '13'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1038/ncomms11552
ec_funded: 1
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oa: 1
oa_version: Published Version
project:
- _id: 25C26B1E-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P24909-B24
  name: Mechanisms of transmitter release at GABAergic synapses
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  call_identifier: FP7
  grant_number: '268548'
  name: Nanophysiology of fast-spiking, parvalbumin-expressing GABAergic interneurons
publication: Nature Communications
publication_status: published
publisher: Nature Publishing Group
publist_id: '5766'
pubrep_id: '582'
quality_controlled: '1'
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    relation: dissertation_contains
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scopus_import: 1
status: public
title: Symmetric spike timing-dependent plasticity at CA3–CA3 synapses optimizes storage
  and recall in autoassociative networks
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 7
year: '2016'
...
---
_id: '1396'
abstract:
- lang: eng
  text: CA3 pyramidal neurons are thought to pay a key role in memory storage and
    pattern completion by activity-dependent synaptic plasticity between CA3-CA3 recurrent
    excitatory synapses. To examine the induction rules of synaptic plasticity at
    CA3-CA3 synapses, we performed whole-cell patch-clamp recordings in acute hippocampal
    slices from rats (postnatal 21-24 days) at room temperature. Compound excitatory
    postsynaptic potentials (ESPSs) were recorded by tract stimulation in stratum
    oriens in the presence of 10 µM gabazine. High-frequency stimulation (HFS) induced
    N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP). Although
    LTP by HFS did not requier postsynaptic spikes, it was blocked by Na+-channel
    blockers suggesting that local active processes (e.g.) dendritic spikes) may contribute
    to LTP induction without requirement of a somatic action potential (AP). We next
    examined the properties of spike timing-dependent plasticity (STDP) at CA3-CA3
    synapses. Unexpectedly, low-frequency pairing of EPSPs and backpropagated action
    potentialy (bAPs) induced LTP, independent of temporal order. The STDP curve was
    symmetric and broad, with a half-width of ~150 ms. Consistent with these specific
    STDP induction properties, post-presynaptic sequences led to a supralinear summation
    of spine [Ca2+] transients. Furthermore, in autoassociative network models, storage
    and recall was substantially more robust with symmetric than with asymmetric STDP
    rules. In conclusion, we found associative forms of LTP at CA3-CA3 recurrent collateral
    synapses with distinct induction rules. LTP induced by HFS may be associated with
    dendritic spikes. In contrast, low frequency pairing of pre- and postsynaptic
    activity induced LTP only if EPSP-AP were temporally very close. Together, these
    induction mechanisms of synaptiic plasticity may contribute to memory storage
    in the CA3-CA3 microcircuit at different ranges of activity.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Rajiv Kumar
  full_name: Mishra, Rajiv Kumar
  id: 46CB58F2-F248-11E8-B48F-1D18A9856A87
  last_name: Mishra
citation:
  ama: Mishra RK. Synaptic plasticity rules at CA3-CA3 recurrent synapses in hippocampus.
    2016.
  apa: Mishra, R. K. (2016). <i>Synaptic plasticity rules at CA3-CA3 recurrent synapses
    in hippocampus</i>. Institute of Science and Technology Austria.
  chicago: Mishra, Rajiv Kumar. “Synaptic Plasticity Rules at CA3-CA3 Recurrent Synapses
    in Hippocampus.” Institute of Science and Technology Austria, 2016.
  ieee: R. K. Mishra, “Synaptic plasticity rules at CA3-CA3 recurrent synapses in
    hippocampus,” Institute of Science and Technology Austria, 2016.
  ista: Mishra RK. 2016. Synaptic plasticity rules at CA3-CA3 recurrent synapses in
    hippocampus. Institute of Science and Technology Austria.
  mla: Mishra, Rajiv Kumar. <i>Synaptic Plasticity Rules at CA3-CA3 Recurrent Synapses
    in Hippocampus</i>. Institute of Science and Technology Austria, 2016.
  short: R.K. Mishra, Synaptic Plasticity Rules at CA3-CA3 Recurrent Synapses in Hippocampus,
    Institute of Science and Technology Austria, 2016.
date_created: 2018-12-11T11:51:46Z
date_published: 2016-03-01T00:00:00Z
date_updated: 2023-09-07T11:55:26Z
day: '01'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: PeJo
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month: '03'
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oa_version: Published Version
page: '83'
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '5811'
related_material:
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    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
title: Synaptic plasticity rules at CA3-CA3 recurrent synapses in hippocampus
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2016'
...