---
_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. Scientific Reports. 2021;11. doi:10.1038/s41598-020-80507-7
apa: Pandey, R., Al-Nuaimi, Y., Mishra, R. K., Spurgeon, S. K., & 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. Springer
Nature. https://doi.org/10.1038/s41598-020-80507-7
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.” Scientific Reports.
Springer Nature, 2021. https://doi.org/10.1038/s41598-020-80507-7.
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,” Scientific Reports, 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.” Scientific
Reports, vol. 11, 2204, Springer Nature, 2021, doi:10.1038/s41598-020-80507-7.
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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oa_version: Published Version
publication: Scientific Reports
publication_identifier:
eissn:
- '20452322'
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
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.
Nature Communications. 2016;7. doi:10.1038/ncomms11552
apa: Mishra, R. K., Kim, S., Guzmán, J., & Jonas, P. M. (2016). Symmetric spike
timing-dependent plasticity at CA3–CA3 synapses optimizes storage and recall in
autoassociative networks. Nature Communications. Nature Publishing Group.
https://doi.org/10.1038/ncomms11552
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.” Nature Communications. Nature Publishing
Group, 2016. https://doi.org/10.1038/ncomms11552.
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,” Nature Communications, 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.” Nature
Communications, vol. 7, 11552, Nature Publishing Group, 2016, doi:10.1038/ncomms11552.
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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month: '05'
oa: 1
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project:
- _id: 25C26B1E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P24909-B24
name: Mechanisms of transmitter release at GABAergic synapses
- _id: 25C0F108-B435-11E9-9278-68D0E5697425
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'
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quality_controlled: '1'
related_material:
record:
- id: '1396'
relation: dissertation_contains
status: public
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). Synaptic plasticity rules at CA3-CA3 recurrent synapses
in hippocampus. 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. Synaptic Plasticity Rules at CA3-CA3 Recurrent Synapses
in Hippocampus. 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:
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degree_awarded: PhD
department:
- _id: PeJo
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issn:
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publisher: Institute of Science and Technology Austria
publist_id: '5811'
related_material:
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relation: part_of_dissertation
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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'
...