---
_id: '6848'
abstract:
- lang: eng
text: Proton-translocating transhydrogenase (also known as nicotinamide nucleotide
transhydrogenase (NNT)) is found in the plasma membranes of bacteria and the inner
mitochondrial membranes of eukaryotes. NNT catalyses the transfer of a hydride
between NADH and NADP+, coupled to the translocation of one proton across the
membrane. Its main physiological function is the generation of NADPH, which is
a substrate in anabolic reactions and a regulator of oxidative status; however,
NNT may also fine-tune the Krebs cycle1,2. NNT deficiency causes familial glucocorticoid
deficiency in humans and metabolic abnormalities in mice, similar to those observed
in type II diabetes3,4. The catalytic mechanism of NNT has been proposed to involve
a rotation of around 180° of the entire NADP(H)-binding domain that alternately
participates in hydride transfer and proton-channel gating. However, owing to
the lack of high-resolution structures of intact NNT, the details of this process
remain unclear5,6. Here we present the cryo-electron microscopy structure of intact
mammalian NNT in different conformational states. We show how the NADP(H)-binding
domain opens the proton channel to the opposite sides of the membrane, and we
provide structures of these two states. We also describe the catalytically important
interfaces and linkers between the membrane and the soluble domains and their
roles in nucleotide exchange. These structures enable us to propose a revised
mechanism for a coupling process in NNT that is consistent with a large body of
previous biochemical work. Our results are relevant to the development of currently
unavailable NNT inhibitors, which may have therapeutic potential in ischaemia
reperfusion injury, metabolic syndrome and some cancers7,8,9.
acknowledged_ssus:
- _id: ScienComp
acknowledgement: " We thank R. Thompson, G. Effantin and V.-V. Hodirnau for their
assistance with collecting NADP+, NADPH and apo datasets, respectively. Data processing
was performed at the IST high-performance computing cluster.\r\nThis project has
received funding from the European Union’s Horizon 2020 research and innovation
programme under the Marie Skłodowska-Curie Grant Agreement no. 665385."
article_processing_charge: No
article_type: letter_note
author:
- first_name: Domen
full_name: Kampjut, Domen
id: 37233050-F248-11E8-B48F-1D18A9856A87
last_name: Kampjut
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
citation:
ama: Kampjut D, Sazanov LA. Structure and mechanism of mitochondrial proton-translocating
transhydrogenase. Nature. 2019;573(7773):291–295. doi:10.1038/s41586-019-1519-2
apa: Kampjut, D., & Sazanov, L. A. (2019). Structure and mechanism of mitochondrial
proton-translocating transhydrogenase. Nature. Springer Nature. https://doi.org/10.1038/s41586-019-1519-2
chicago: Kampjut, Domen, and Leonid A Sazanov. “Structure and Mechanism of Mitochondrial
Proton-Translocating Transhydrogenase.” Nature. Springer Nature, 2019.
https://doi.org/10.1038/s41586-019-1519-2.
ieee: D. Kampjut and L. A. Sazanov, “Structure and mechanism of mitochondrial proton-translocating
transhydrogenase,” Nature, vol. 573, no. 7773. Springer Nature, pp. 291–295,
2019.
ista: Kampjut D, Sazanov LA. 2019. Structure and mechanism of mitochondrial proton-translocating
transhydrogenase. Nature. 573(7773), 291–295.
mla: Kampjut, Domen, and Leonid A. Sazanov. “Structure and Mechanism of Mitochondrial
Proton-Translocating Transhydrogenase.” Nature, vol. 573, no. 7773, Springer
Nature, 2019, pp. 291–295, doi:10.1038/s41586-019-1519-2.
short: D. Kampjut, L.A. Sazanov, Nature 573 (2019) 291–295.
date_created: 2019-09-04T06:21:41Z
date_published: 2019-09-12T00:00:00Z
date_updated: 2024-03-27T23:30:14Z
day: '12'
ddc:
- '572'
department:
- _id: LeSa
doi: 10.1038/s41586-019-1519-2
ec_funded: 1
external_id:
isi:
- '000485415400061'
pmid:
- '31462775'
file:
- access_level: open_access
checksum: 52728cda5210a3e9b74cc204e8aed3d5
content_type: application/pdf
creator: lsazanov
date_created: 2020-11-26T16:33:44Z
date_updated: 2020-11-26T16:33:44Z
file_id: '8821'
file_name: Manuscript_final_acc_withFigs_SI_opt_red.pdf
file_size: 3066206
relation: main_file
success: 1
file_date_updated: 2020-11-26T16:33:44Z
has_accepted_license: '1'
intvolume: ' 573'
isi: 1
issue: '7773'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Submitted Version
page: 291–295
pmid: 1
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication: Nature
publication_identifier:
eissn:
- 1476-4687
issn:
- 0028-0836
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on IST Website
relation: press_release
url: https://ist.ac.at/en/news/high-end-microscopy-reveals-structure-and-function-of-crucial-metabolic-enzyme/
record:
- id: '8340'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Structure and mechanism of mitochondrial proton-translocating transhydrogenase
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 573
year: '2019'
...
---
_id: '6194'
abstract:
- lang: eng
text: Grid cells with their rigid hexagonal firing fields are thought to provide
an invariant metric to the hippocampal cognitive map, yet environmental geometrical
features have recently been shown to distort the grid structure. Given that the
hippocampal role goes beyond space, we tested the influence of nonspatial information
on the grid organization. We trained rats to daily learn three new reward locations
on a cheeseboard maze while recording from the medial entorhinal cortex and the
hippocampal CA1 region. Many grid fields moved toward goal location, leading to
long-lasting deformations of the entorhinal map. Therefore, distortions in the
grid structure contribute to goal representation during both learning and recall,
which demonstrates that grid cells participate in mnemonic coding and do not merely
provide a simple metric of space.
article_processing_charge: No
article_type: original
author:
- first_name: Charlotte N.
full_name: Boccara, Charlotte N.
id: 3FC06552-F248-11E8-B48F-1D18A9856A87
last_name: Boccara
orcid: 0000-0001-7237-5109
- first_name: Michele
full_name: Nardin, Michele
id: 30BD0376-F248-11E8-B48F-1D18A9856A87
last_name: Nardin
orcid: 0000-0001-8849-6570
- first_name: Federico
full_name: Stella, Federico
id: 39AF1E74-F248-11E8-B48F-1D18A9856A87
last_name: Stella
orcid: 0000-0001-9439-3148
- first_name: Joseph
full_name: O'Neill, Joseph
id: 426376DC-F248-11E8-B48F-1D18A9856A87
last_name: O'Neill
- first_name: Jozsef L
full_name: Csicsvari, Jozsef L
id: 3FA14672-F248-11E8-B48F-1D18A9856A87
last_name: Csicsvari
orcid: 0000-0002-5193-4036
citation:
ama: Boccara CN, Nardin M, Stella F, O’Neill J, Csicsvari JL. The entorhinal cognitive
map is attracted to goals. Science. 2019;363(6434):1443-1447. doi:10.1126/science.aav4837
apa: Boccara, C. N., Nardin, M., Stella, F., O’Neill, J., & Csicsvari, J. L.
(2019). The entorhinal cognitive map is attracted to goals. Science. American
Association for the Advancement of Science. https://doi.org/10.1126/science.aav4837
chicago: Boccara, Charlotte N., Michele Nardin, Federico Stella, Joseph O’Neill,
and Jozsef L Csicsvari. “The Entorhinal Cognitive Map Is Attracted to Goals.”
Science. American Association for the Advancement of Science, 2019. https://doi.org/10.1126/science.aav4837.
ieee: C. N. Boccara, M. Nardin, F. Stella, J. O’Neill, and J. L. Csicsvari, “The
entorhinal cognitive map is attracted to goals,” Science, vol. 363, no.
6434. American Association for the Advancement of Science, pp. 1443–1447, 2019.
ista: Boccara CN, Nardin M, Stella F, O’Neill J, Csicsvari JL. 2019. The entorhinal
cognitive map is attracted to goals. Science. 363(6434), 1443–1447.
mla: Boccara, Charlotte N., et al. “The Entorhinal Cognitive Map Is Attracted to
Goals.” Science, vol. 363, no. 6434, American Association for the Advancement
of Science, 2019, pp. 1443–47, doi:10.1126/science.aav4837.
short: C.N. Boccara, M. Nardin, F. Stella, J. O’Neill, J.L. Csicsvari, Science 363
(2019) 1443–1447.
date_created: 2019-04-04T08:39:30Z
date_published: 2019-03-29T00:00:00Z
date_updated: 2024-03-27T23:30:16Z
day: '29'
ddc:
- '570'
department:
- _id: JoCs
doi: 10.1126/science.aav4837
ec_funded: 1
external_id:
isi:
- '000462738000034'
file:
- access_level: open_access
checksum: 5e6b16742cde10a560cfaf2130764da1
content_type: application/pdf
creator: dernst
date_created: 2020-05-14T09:11:10Z
date_updated: 2020-07-14T12:47:23Z
file_id: '7826'
file_name: 2019_Science_Boccara.pdf
file_size: 9045923
relation: main_file
file_date_updated: 2020-07-14T12:47:23Z
has_accepted_license: '1'
intvolume: ' 363'
isi: 1
issue: '6434'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Submitted Version
page: 1443-1447
project:
- _id: 257A4776-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '281511'
name: Memory-related information processing in neuronal circuits of the hippocampus
and entorhinal cortex
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication: Science
publication_identifier:
eissn:
- 1095-9203
issn:
- 0036-8075
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/grid-cells-create-treasure-map-in-rat-brain/
record:
- id: '6062'
relation: popular_science
status: public
- id: '11932'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: The entorhinal cognitive map is attracted to goals
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 363
year: '2019'
...
---
_id: '7132'
abstract:
- lang: eng
text: "A major challenge in neuroscience research is to dissect the circuits that
orchestrate behavior in health and disease. Proteins from a wide range of non-mammalian
species, such as microbial opsins, have been successfully transplanted to specific
neuronal targets to override their natural communication patterns. The goal of
our work is to manipulate synaptic communication in a manner that closely incorporates
the functional intricacies of synapses by preserving temporal encoding (i.e. the
firing pattern of the presynaptic neuron) and connectivity (i.e. target specific
synapses rather than specific neurons). Our strategy to achieve this goal builds
on the use of non-mammalian transplants to create a synthetic synapse. The mode
of modulation comes from pre-synaptic uptake of a synthetic neurotransmitter (SN)
into synaptic vesicles by means of a genetically targeted transporter selective
for the SN. Upon natural vesicular release, exposure of the SN to the synaptic
cleft will modify the post-synaptic potential through an orthogonal ligand gated
ion channel. To achieve this goal we have functionally characterized a mixed cationic
methionine-gated ion channel from Arabidopsis thaliana, designed a method to functionally
characterize a synthetic transporter in isolated synaptic vesicles without the
need for transgenic animals, identified and extracted multiple prokaryotic uptake
systems that are substrate specific for methionine (Met), and established a primary/cell
line co-culture system that would allow future combinatorial testing of this orthogonal
transmitter-transporter-channel trifecta.\r\nSynthetic synapses will provide a
unique opportunity to manipulate synaptic communication while maintaining the
electrophysiological integrity of the pre-synaptic cell. In this way, information
may be preserved that was generated in upstream circuits and that could be essential
for concerted function and information processing."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Catherine
full_name: Mckenzie, Catherine
id: 3EEDE19A-F248-11E8-B48F-1D18A9856A87
last_name: Mckenzie
citation:
ama: Mckenzie C. Design and characterization of methods and biological components
to realize synthetic neurotransmission. 2019. doi:10.15479/at:ista:7132
apa: Mckenzie, C. (2019). Design and characterization of methods and biological
components to realize synthetic neurotransmission. Institute of Science and
Technology Austria. https://doi.org/10.15479/at:ista:7132
chicago: Mckenzie, Catherine. “Design and Characterization of Methods and Biological
Components to Realize Synthetic Neurotransmission.” Institute of Science and Technology
Austria, 2019. https://doi.org/10.15479/at:ista:7132.
ieee: C. Mckenzie, “Design and characterization of methods and biological components
to realize synthetic neurotransmission,” Institute of Science and Technology Austria,
2019.
ista: Mckenzie C. 2019. Design and characterization of methods and biological components
to realize synthetic neurotransmission. Institute of Science and Technology Austria.
mla: Mckenzie, Catherine. Design and Characterization of Methods and Biological
Components to Realize Synthetic Neurotransmission. Institute of Science and
Technology Austria, 2019, doi:10.15479/at:ista:7132.
short: C. Mckenzie, Design and Characterization of Methods and Biological Components
to Realize Synthetic Neurotransmission, Institute of Science and Technology Austria,
2019.
date_created: 2019-11-27T09:07:14Z
date_published: 2019-06-27T00:00:00Z
date_updated: 2024-03-27T23:30:21Z
day: '27'
ddc:
- '571'
- '573'
degree_awarded: PhD
department:
- _id: HaJa
doi: 10.15479/at:ista:7132
file:
- access_level: closed
checksum: 34d0fe0f6e0af97b5937205a3e350423
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: dernst
date_created: 2019-11-27T09:06:10Z
date_updated: 2020-07-14T12:47:50Z
file_id: '7133'
file_name: McKenzie PhD Thesis August 2018 - Corrected Final.docx
file_size: 5054633
relation: source_file
- access_level: open_access
checksum: 140dfb5e3df7edca34f4b6fcc55d876f
content_type: application/pdf
creator: dernst
date_created: 2019-11-27T09:06:10Z
date_updated: 2020-07-14T12:47:50Z
file_id: '7134'
file_name: McKenzie PhD Thesis August 2018 - Corrected Final.pdf
file_size: 3231837
relation: main_file
file_date_updated: 2020-07-14T12:47:50Z
has_accepted_license: '1'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: '95'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '6266'
relation: old_edition
status: public
status: public
supervisor:
- first_name: Harald L
full_name: Janovjak, Harald L
id: 33BA6C30-F248-11E8-B48F-1D18A9856A87
last_name: Janovjak
orcid: 0000-0002-8023-9315
title: Design and characterization of methods and biological components to realize
synthetic neurotransmission
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2019'
...
---
_id: '5949'
abstract:
- lang: eng
text: Aberrant proteostasis of protein aggregation may lead to behavior disorders
including chronic mental illnesses (CMI). Furthermore, the neuronal activity alterations
that underlie CMI are not well understood. We recorded the local field potential
and single-unit activity of the hippocampal CA1 region in vivo in rats transgenically
overexpressing the Disrupted-in-Schizophrenia 1 (DISC1) gene (tgDISC1), modeling
sporadic CMI. These tgDISC1 rats have previously been shown to exhibit DISC1 protein
aggregation, disturbances in the dopaminergic system and attention-related deficits.
Recordings were performed during exploration of familiar and novel open field
environments and during sleep, allowing investigation of neuronal abnormalities
in unconstrained behavior. Compared to controls, tgDISC1 place cells exhibited
smaller place fields and decreased speed-modulation of their firing rates, demonstrating
altered spatial coding and deficits in encoding location-independent sensory inputs.
Oscillation analyses showed that tgDISC1 pyramidal neurons had higher theta phase
locking strength during novelty, limiting their phase coding ability. However,
their mean theta phases were more variable at the population level, reducing oscillatory
network synchronization. Finally, tgDISC1 pyramidal neurons showed a lack of novelty-induced
shift in their preferred theta and gamma firing phases, indicating deficits in
coding of novel environments with oscillatory firing. By combining single cell
and neuronal population analyses, we link DISC1 protein pathology with abnormal
hippocampal neural coding and network synchrony, and thereby gain a more comprehensive
understanding of CMI mechanisms.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Karola
full_name: Käfer, Karola
id: 2DAA49AA-F248-11E8-B48F-1D18A9856A87
last_name: Käfer
- first_name: Hugo
full_name: Malagon-Vina, Hugo
last_name: Malagon-Vina
- first_name: Desiree
full_name: Dickerson, Desiree
id: 444EB89E-F248-11E8-B48F-1D18A9856A87
last_name: Dickerson
- first_name: Joseph
full_name: O'Neill, Joseph
last_name: O'Neill
- first_name: Svenja V.
full_name: Trossbach, Svenja V.
last_name: Trossbach
- first_name: Carsten
full_name: Korth, Carsten
last_name: Korth
- first_name: Jozsef L
full_name: Csicsvari, Jozsef L
id: 3FA14672-F248-11E8-B48F-1D18A9856A87
last_name: Csicsvari
orcid: 0000-0002-5193-4036
citation:
ama: Käfer K, Malagon-Vina H, Dickerson D, et al. Disrupted-in-schizophrenia 1 overexpression
disrupts hippocampal coding and oscillatory synchronization. Hippocampus.
2019;29(9):802-816. doi:10.1002/hipo.23076
apa: Käfer, K., Malagon-Vina, H., Dickerson, D., O’Neill, J., Trossbach, S. V.,
Korth, C., & Csicsvari, J. L. (2019). Disrupted-in-schizophrenia 1 overexpression
disrupts hippocampal coding and oscillatory synchronization. Hippocampus.
Wiley. https://doi.org/10.1002/hipo.23076
chicago: Käfer, Karola, Hugo Malagon-Vina, Desiree Dickerson, Joseph O’Neill, Svenja
V. Trossbach, Carsten Korth, and Jozsef L Csicsvari. “Disrupted-in-Schizophrenia
1 Overexpression Disrupts Hippocampal Coding and Oscillatory Synchronization.”
Hippocampus. Wiley, 2019. https://doi.org/10.1002/hipo.23076.
ieee: K. Käfer et al., “Disrupted-in-schizophrenia 1 overexpression disrupts
hippocampal coding and oscillatory synchronization,” Hippocampus, vol.
29, no. 9. Wiley, pp. 802–816, 2019.
ista: Käfer K, Malagon-Vina H, Dickerson D, O’Neill J, Trossbach SV, Korth C, Csicsvari
JL. 2019. Disrupted-in-schizophrenia 1 overexpression disrupts hippocampal coding
and oscillatory synchronization. Hippocampus. 29(9), 802–816.
mla: Käfer, Karola, et al. “Disrupted-in-Schizophrenia 1 Overexpression Disrupts
Hippocampal Coding and Oscillatory Synchronization.” Hippocampus, vol.
29, no. 9, Wiley, 2019, pp. 802–16, doi:10.1002/hipo.23076.
short: K. Käfer, H. Malagon-Vina, D. Dickerson, J. O’Neill, S.V. Trossbach, C. Korth,
J.L. Csicsvari, Hippocampus 29 (2019) 802–816.
date_created: 2019-02-10T22:59:18Z
date_published: 2019-09-01T00:00:00Z
date_updated: 2024-03-27T23:30:22Z
day: '01'
ddc:
- '570'
department:
- _id: JoCs
doi: 10.1002/hipo.23076
ec_funded: 1
external_id:
isi:
- '000480635400003'
file:
- access_level: open_access
checksum: 5e8de271ca04aef92a5de42d6aac4404
content_type: application/pdf
creator: dernst
date_created: 2019-02-11T10:42:51Z
date_updated: 2020-07-14T12:47:13Z
file_id: '5950'
file_name: 2019_Hippocampus_Kaefer.pdf
file_size: 2132893
relation: main_file
file_date_updated: 2020-07-14T12:47:13Z
has_accepted_license: '1'
intvolume: ' 29'
isi: 1
issue: '9'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: 802-816
project:
- _id: 257BBB4C-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '607616'
name: Inter-and intracellular signalling in schizophrenia
publication: Hippocampus
publication_status: published
publisher: Wiley
quality_controlled: '1'
related_material:
record:
- id: '6825'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Disrupted-in-schizophrenia 1 overexpression disrupts hippocampal coding and
oscillatory synchronization
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 29
year: '2019'
...
---
_id: '6825'
abstract:
- lang: eng
text: "The solving of complex tasks requires the functions of more than one brain
area and their interaction. Whilst spatial navigation and memory is dependent
on the hippocampus, flexible behavior relies on the medial prefrontal cortex (mPFC).
To further examine the roles of the hippocampus and mPFC, we recorded their neural
activity during a task that depends on both of these brain regions.\r\nWith tetrodes,
we recorded the extracellular activity of dorsal hippocampal CA1 (HPC) and mPFC
neurons in Long-Evans rats performing a rule-switching task on the plus-maze.
The plus-maze task had a spatial component since it required navigation along
one of the two start arms and at the maze center a choice between one of the two
goal arms. Which goal contained a reward depended on the rule currently in place.
After an uncued rule change the animal had to abandon the old strategy and switch
to the new rule, testing cognitive flexibility. Investigating the coordination
of activity between the HPC and mPFC allows determination during which task stages
their interaction is required. Additionally, comparing neural activity patterns
in these two brain regions allows delineation of the specialized functions of
the HPC and mPFC in this task. We analyzed neural activity in the HPC and mPFC
in terms of oscillatory interactions, rule coding and replay.\r\nWe found that
theta coherence between the HPC and mPFC is increased at the center and goals
of the maze, both when the rule was stable or has changed. Similar results were
found for locking of HPC and mPFC neurons to HPC theta oscillations. However,
no differences in HPC-mPFC theta coordination were observed between the spatially-
and cue-guided rule. Phase locking of HPC and mPFC neurons to HPC gamma oscillations
was not modulated by\r\nmaze position or rule type. We found that the HPC coded
for the two different rules with cofiring relationships between\r\ncell pairs.
However, we could not find conclusive evidence for rule coding in the mPFC. Spatially-selective
firing in the mPFC generalized between the two start and two goal arms. With Bayesian
positional decoding, we found that the mPFC reactivated non-local positions during
awake immobility periods. Replay of these non-local positions could represent
entire behavioral trajectories resembling trajectory replay of the HPC. Furthermore,
mPFC\r\ntrajectory-replay at the goal positively correlated with rule-switching
performance. \r\nFinally, HPC and mPFC trajectory replay occurred independently
of each other. These results show that the mPFC can replay ordered patterns of
activity during awake immobility, possibly underlying its role in flexible behavior. "
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Karola
full_name: Käfer, Karola
id: 2DAA49AA-F248-11E8-B48F-1D18A9856A87
last_name: Käfer
citation:
ama: Käfer K. The hippocampus and medial prefrontal cortex during flexible behavior.
2019. doi:10.15479/AT:ISTA:6825
apa: Käfer, K. (2019). The hippocampus and medial prefrontal cortex during flexible
behavior. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6825
chicago: Käfer, Karola. “The Hippocampus and Medial Prefrontal Cortex during Flexible
Behavior.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6825.
ieee: K. Käfer, “The hippocampus and medial prefrontal cortex during flexible behavior,”
Institute of Science and Technology Austria, 2019.
ista: Käfer K. 2019. The hippocampus and medial prefrontal cortex during flexible
behavior. Institute of Science and Technology Austria.
mla: Käfer, Karola. The Hippocampus and Medial Prefrontal Cortex during Flexible
Behavior. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6825.
short: K. Käfer, The Hippocampus and Medial Prefrontal Cortex during Flexible Behavior,
Institute of Science and Technology Austria, 2019.
date_created: 2019-08-21T15:00:57Z
date_published: 2019-08-24T00:00:00Z
date_updated: 2023-09-07T13:01:42Z
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ddc:
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degree_awarded: PhD
department:
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doi: 10.15479/AT:ISTA:6825
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page: '89'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '5949'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Jozsef L
full_name: Csicsvari, Jozsef L
id: 3FA14672-F248-11E8-B48F-1D18A9856A87
last_name: Csicsvari
orcid: 0000-0002-5193-4036
title: The hippocampus and medial prefrontal cortex during flexible behavior
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2019'
...
---
_id: '6713'
abstract:
- lang: eng
text: Evolutionary studies are often limited by missing data that are critical to
understanding the history of selection. Selection experiments, which reproduce
rapid evolution under controlled conditions, are excellent tools to study how
genomes evolve under selection. Here we present a genomic dissection of the Longshanks
selection experiment, in which mice were selectively bred over 20 generations
for longer tibiae relative to body mass, resulting in 13% longer tibiae in two
replicates. We synthesized evolutionary theory, genome sequences and molecular
genetics to understand the selection response and found that it involved both
polygenic adaptation and discrete loci of major effect, with the strongest loci
tending to be selected in parallel between replicates. We show that selection
may favor de-repression of bone growth through inactivating two limb enhancers
of an inhibitor, Nkx3-2. Our integrative genomic analyses thus show that it is
possible to connect individual base-pair changes to the overall selection response.
article_number: e42014
article_processing_charge: No
author:
- first_name: João Pl
full_name: Castro, João Pl
last_name: Castro
- first_name: Michelle N.
full_name: Yancoskie, Michelle N.
last_name: Yancoskie
- first_name: Marta
full_name: Marchini, Marta
last_name: Marchini
- first_name: Stefanie
full_name: Belohlavy, Stefanie
id: 43FE426A-F248-11E8-B48F-1D18A9856A87
last_name: Belohlavy
orcid: 0000-0002-9849-498X
- first_name: Layla
full_name: Hiramatsu, Layla
last_name: Hiramatsu
- first_name: Marek
full_name: Kučka, Marek
last_name: Kučka
- first_name: William H.
full_name: Beluch, William H.
last_name: Beluch
- first_name: Ronald
full_name: Naumann, Ronald
last_name: Naumann
- first_name: Isabella
full_name: Skuplik, Isabella
last_name: Skuplik
- first_name: John
full_name: Cobb, John
last_name: Cobb
- first_name: Nicholas H
full_name: Barton, Nicholas H
id: 4880FE40-F248-11E8-B48F-1D18A9856A87
last_name: Barton
orcid: 0000-0002-8548-5240
- first_name: Campbell
full_name: Rolian, Campbell
last_name: Rolian
- first_name: Yingguang Frank
full_name: Chan, Yingguang Frank
last_name: Chan
citation:
ama: Castro JP, Yancoskie MN, Marchini M, et al. An integrative genomic analysis
of the Longshanks selection experiment for longer limbs in mice. eLife.
2019;8. doi:10.7554/eLife.42014
apa: Castro, J. P., Yancoskie, M. N., Marchini, M., Belohlavy, S., Hiramatsu, L.,
Kučka, M., … Chan, Y. F. (2019). An integrative genomic analysis of the Longshanks
selection experiment for longer limbs in mice. ELife. eLife Sciences Publications.
https://doi.org/10.7554/eLife.42014
chicago: Castro, João Pl, Michelle N. Yancoskie, Marta Marchini, Stefanie Belohlavy,
Layla Hiramatsu, Marek Kučka, William H. Beluch, et al. “An Integrative Genomic
Analysis of the Longshanks Selection Experiment for Longer Limbs in Mice.” ELife.
eLife Sciences Publications, 2019. https://doi.org/10.7554/eLife.42014.
ieee: J. P. Castro et al., “An integrative genomic analysis of the Longshanks
selection experiment for longer limbs in mice,” eLife, vol. 8. eLife Sciences
Publications, 2019.
ista: Castro JP, Yancoskie MN, Marchini M, Belohlavy S, Hiramatsu L, Kučka M, Beluch
WH, Naumann R, Skuplik I, Cobb J, Barton NH, Rolian C, Chan YF. 2019. An integrative
genomic analysis of the Longshanks selection experiment for longer limbs in mice.
eLife. 8, e42014.
mla: Castro, João Pl, et al. “An Integrative Genomic Analysis of the Longshanks
Selection Experiment for Longer Limbs in Mice.” ELife, vol. 8, e42014,
eLife Sciences Publications, 2019, doi:10.7554/eLife.42014.
short: J.P. Castro, M.N. Yancoskie, M. Marchini, S. Belohlavy, L. Hiramatsu, M.
Kučka, W.H. Beluch, R. Naumann, I. Skuplik, J. Cobb, N.H. Barton, C. Rolian, Y.F.
Chan, ELife 8 (2019).
date_created: 2019-07-28T21:59:17Z
date_published: 2019-06-06T00:00:00Z
date_updated: 2024-03-27T23:30:22Z
day: '06'
ddc:
- '576'
department:
- _id: NiBa
doi: 10.7554/eLife.42014
external_id:
isi:
- '000473588700001'
pmid:
- '31169497'
file:
- access_level: open_access
checksum: fa0936fe58f0d9e3f8e75038570e5a17
content_type: application/pdf
creator: apreinsp
date_created: 2019-07-29T07:41:18Z
date_updated: 2020-07-14T12:47:38Z
file_id: '6721'
file_name: 2019_eLife_Castro.pdf
file_size: 6748249
relation: main_file
file_date_updated: 2020-07-14T12:47:38Z
has_accepted_license: '1'
intvolume: ' 8'
isi: 1
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
record:
- id: '9804'
relation: research_data
status: public
- id: '11388'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: An integrative genomic analysis of the Longshanks selection experiment for
longer limbs in mice
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 8
year: '2019'
...
---
_id: '10065'
abstract:
- lang: eng
text: We study double quantum dots in a Ge/SiGe heterostructure and test their maturity
towards singlet-triplet ($S-T_0$) qubits. We demonstrate a large range of tunability,
from two single quantum dots to a double quantum dot. We measure Pauli spin blockade
and study the anisotropy of the $g$-factor. We use an adjacent quantum dot for
sensing charge transitions in the double quantum dot at interest. In conclusion,
Ge/SiGe possesses all ingredients necessary for building a singlet-triplet qubit.
acknowledged_ssus:
- _id: M-Shop
- _id: NanoFab
acknowledgement: "We thank Matthias Brauns for helpful discussions and careful proofreading
of the manuscript. This project has received funding from the European Union’s Horizon
2020 research and innovation program under the Marie Sklodowska-Curie grant agreement
No 844511 and from the FWF project P30207. The research was supported by the Scientific
Service Units of IST Austria through resources provided by the MIBA machine shop
and the nanofabrication\r\nfacility."
article_number: '1910.05841'
article_processing_charge: No
author:
- first_name: Andrea C
full_name: Hofmann, Andrea C
id: 340F461A-F248-11E8-B48F-1D18A9856A87
last_name: Hofmann
- first_name: Daniel
full_name: Jirovec, Daniel
id: 4C473F58-F248-11E8-B48F-1D18A9856A87
last_name: Jirovec
orcid: 0000-0002-7197-4801
- first_name: Maxim
full_name: Borovkov, Maxim
last_name: Borovkov
- first_name: Ivan
full_name: Prieto Gonzalez, Ivan
id: 2A307FE2-F248-11E8-B48F-1D18A9856A87
last_name: Prieto Gonzalez
orcid: 0000-0002-7370-5357
- first_name: Andrea
full_name: Ballabio, Andrea
last_name: Ballabio
- first_name: Jacopo
full_name: Frigerio, Jacopo
last_name: Frigerio
- first_name: Daniel
full_name: Chrastina, Daniel
last_name: Chrastina
- first_name: Giovanni
full_name: Isella, Giovanni
last_name: Isella
- first_name: Georgios
full_name: Katsaros, Georgios
id: 38DB5788-F248-11E8-B48F-1D18A9856A87
last_name: Katsaros
orcid: 0000-0001-8342-202X
citation:
ama: Hofmann AC, Jirovec D, Borovkov M, et al. Assessing the potential of Ge/SiGe
quantum dots as hosts for singlet-triplet qubits. arXiv. doi:10.48550/arXiv.1910.05841
apa: Hofmann, A. C., Jirovec, D., Borovkov, M., Prieto Gonzalez, I., Ballabio, A.,
Frigerio, J., … Katsaros, G. (n.d.). Assessing the potential of Ge/SiGe quantum
dots as hosts for singlet-triplet qubits. arXiv. https://doi.org/10.48550/arXiv.1910.05841
chicago: Hofmann, Andrea C, Daniel Jirovec, Maxim Borovkov, Ivan Prieto Gonzalez,
Andrea Ballabio, Jacopo Frigerio, Daniel Chrastina, Giovanni Isella, and Georgios
Katsaros. “Assessing the Potential of Ge/SiGe Quantum Dots as Hosts for Singlet-Triplet
Qubits.” ArXiv, n.d. https://doi.org/10.48550/arXiv.1910.05841.
ieee: A. C. Hofmann et al., “Assessing the potential of Ge/SiGe quantum dots
as hosts for singlet-triplet qubits,” arXiv. .
ista: Hofmann AC, Jirovec D, Borovkov M, Prieto Gonzalez I, Ballabio A, Frigerio
J, Chrastina D, Isella G, Katsaros G. Assessing the potential of Ge/SiGe quantum
dots as hosts for singlet-triplet qubits. arXiv, 1910.05841.
mla: Hofmann, Andrea C., et al. “Assessing the Potential of Ge/SiGe Quantum Dots
as Hosts for Singlet-Triplet Qubits.” ArXiv, 1910.05841, doi:10.48550/arXiv.1910.05841.
short: A.C. Hofmann, D. Jirovec, M. Borovkov, I. Prieto Gonzalez, A. Ballabio, J.
Frigerio, D. Chrastina, G. Isella, G. Katsaros, ArXiv (n.d.).
date_created: 2021-10-01T12:14:51Z
date_published: 2019-10-13T00:00:00Z
date_updated: 2024-03-27T23:30:26Z
day: '13'
department:
- _id: GeKa
doi: 10.48550/arXiv.1910.05841
ec_funded: 1
external_id:
arxiv:
- '1910.05841'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/1910.05841
month: '10'
oa: 1
oa_version: Preprint
project:
- _id: 26A151DA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '844511'
name: Majorana bound states in Ge/SiGe heterostructures
- _id: 2641CE5E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P30207
name: Hole spin orbit qubits in Ge quantum wells
publication: arXiv
publication_status: submitted
related_material:
record:
- id: '10058'
relation: dissertation_contains
status: public
status: public
title: Assessing the potential of Ge/SiGe quantum dots as hosts for singlet-triplet
qubits
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2019'
...
---
_id: '6187'
abstract:
- lang: eng
text: Aberrant display of the truncated core1 O-glycan T-antigen is a common feature
of human cancer cells that correlates with metastasis. Here we show that T-antigen
in Drosophila melanogaster macrophages is involved in their developmentally programmed
tissue invasion. Higher macrophage T-antigen levels require an atypical major
facilitator superfamily (MFS) member that we named Minerva which enables macrophage
dissemination and invasion. We characterize for the first time the T and Tn glycoform
O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva
increases the presence of T-antigen on proteins in pathways previously linked
to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required
for macrophage tissue entry. Minerva’s vertebrate ortholog, MFSD1, rescues the
minerva mutant’s migration and T-antigen glycosylation defects. We thus identify
a key conserved regulator that orchestrates O-glycosylation on a protein subset
to activate a program governing migration steps important for both development
and cancer metastasis.
acknowledged_ssus:
- _id: LifeSc
article_number: e41801
article_processing_charge: No
author:
- first_name: Katarina
full_name: Valosková, Katarina
id: 46F146FC-F248-11E8-B48F-1D18A9856A87
last_name: Valosková
- first_name: Julia
full_name: Biebl, Julia
id: 3CCBB46E-F248-11E8-B48F-1D18A9856A87
last_name: Biebl
- first_name: Marko
full_name: Roblek, Marko
id: 3047D808-F248-11E8-B48F-1D18A9856A87
last_name: Roblek
orcid: 0000-0001-9588-1389
- first_name: Shamsi
full_name: Emtenani, Shamsi
id: 49D32318-F248-11E8-B48F-1D18A9856A87
last_name: Emtenani
orcid: 0000-0001-6981-6938
- first_name: Attila
full_name: György, Attila
id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87
last_name: György
orcid: 0000-0002-1819-198X
- first_name: Michaela
full_name: Misova, Michaela
id: 495A3C32-F248-11E8-B48F-1D18A9856A87
last_name: Misova
orcid: 0000-0003-2427-6856
- first_name: Aparna
full_name: Ratheesh, Aparna
id: 2F064CFE-F248-11E8-B48F-1D18A9856A87
last_name: Ratheesh
orcid: 0000-0001-7190-0776
- first_name: Patricia
full_name: Rodrigues, Patricia
id: 2CE4065A-F248-11E8-B48F-1D18A9856A87
last_name: Rodrigues
- first_name: Katerina
full_name: Shkarina, Katerina
last_name: Shkarina
- first_name: Ida Signe Bohse
full_name: Larsen, Ida Signe Bohse
last_name: Larsen
- first_name: Sergey Y
full_name: Vakhrushev, Sergey Y
last_name: Vakhrushev
- first_name: Henrik
full_name: Clausen, Henrik
last_name: Clausen
- first_name: Daria E
full_name: Siekhaus, Daria E
id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
last_name: Siekhaus
orcid: 0000-0001-8323-8353
citation:
ama: Valosková K, Bicher J, Roblek M, et al. A conserved major facilitator superfamily
member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion.
eLife. 2019;8. doi:10.7554/elife.41801
apa: Valosková, K., Bicher, J., Roblek, M., Emtenani, S., György, A., Misova, M.,
… Siekhaus, D. E. (2019). A conserved major facilitator superfamily member orchestrates
a subset of O-glycosylation to aid macrophage tissue invasion. ELife. eLife
Sciences Publications. https://doi.org/10.7554/elife.41801
chicago: Valosková, Katarina, Julia Bicher, Marko Roblek, Shamsi Emtenani, Attila
György, Michaela Misova, Aparna Ratheesh, et al. “A Conserved Major Facilitator
Superfamily Member Orchestrates a Subset of O-Glycosylation to Aid Macrophage
Tissue Invasion.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/elife.41801.
ieee: K. Valosková et al., “A conserved major facilitator superfamily member
orchestrates a subset of O-glycosylation to aid macrophage tissue invasion,” eLife,
vol. 8. eLife Sciences Publications, 2019.
ista: Valosková K, Bicher J, Roblek M, Emtenani S, György A, Misova M, Ratheesh
A, Rodrigues P, Shkarina K, Larsen ISB, Vakhrushev SY, Clausen H, Siekhaus DE.
2019. A conserved major facilitator superfamily member orchestrates a subset of
O-glycosylation to aid macrophage tissue invasion. eLife. 8, e41801.
mla: Valosková, Katarina, et al. “A Conserved Major Facilitator Superfamily Member
Orchestrates a Subset of O-Glycosylation to Aid Macrophage Tissue Invasion.” ELife,
vol. 8, e41801, eLife Sciences Publications, 2019, doi:10.7554/elife.41801.
short: K. Valosková, J. Bicher, M. Roblek, S. Emtenani, A. György, M. Misova, A.
Ratheesh, P. Rodrigues, K. Shkarina, I.S.B. Larsen, S.Y. Vakhrushev, H. Clausen,
D.E. Siekhaus, ELife 8 (2019).
date_created: 2019-03-28T13:37:45Z
date_published: 2019-03-26T00:00:00Z
date_updated: 2024-03-27T23:30:29Z
day: '26'
ddc:
- '570'
department:
- _id: DaSi
doi: 10.7554/elife.41801
ec_funded: 1
external_id:
isi:
- '000462530200001'
file:
- access_level: open_access
checksum: cc0d1a512559d52e7e7cb0e9b9854b40
content_type: application/pdf
creator: dernst
date_created: 2019-03-28T14:00:41Z
date_updated: 2020-07-14T12:47:23Z
file_id: '6188'
file_name: 2019_eLife_Valoskova.pdf
file_size: 4496017
relation: main_file
file_date_updated: 2020-07-14T12:47:23Z
has_accepted_license: '1'
intvolume: ' 8'
isi: 1
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
project:
- _id: 253CDE40-B435-11E9-9278-68D0E5697425
grant_number: '24283'
name: Examination of the role of a MFS transporter in the migration of Drosophila
immune cells
- _id: 253B6E48-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29638
name: The role of Drosophila TNF alpha in immune cell invasion
- _id: 2536F660-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '334077'
name: Investigating the role of transporters in invasive migration through junctions
- _id: 25388084-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '329540'
name: 'Breaking barriers: Investigating the junctional and mechanobiological changes
underlying the ability of Drosophila immune cells to invade an epithelium'
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication: eLife
publication_identifier:
issn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/new-gene-potentially-involved-in-metastasis-identified/
record:
- id: '6530'
relation: dissertation_contains
- id: '8983'
relation: dissertation_contains
status: public
- id: '6546'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation
to aid macrophage tissue invasion
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 8
year: '2019'
...
---
_id: '6546'
abstract:
- lang: eng
text: "Invasive migration plays a crucial role not only during development and homeostasis
but also in pathological states, such as tumor metastasis. Drosophila macrophage
migration into the extended germband is an interesting system to study invasive
migration. It carries similarities to immune cell transmigration and cancer cell
invasion, therefore studying this process could also bring new understanding of
invasion in higher organisms. In our work, we uncover a highly conserved member
of the major facilitator family that plays a role in tissue invasion through regulation
of glycosylation on a subgroup of proteins and/or by aiding the precise timing
of DN-Cadherin downregulation. \r\n\r\nAberrant display of the truncated core1
O-glycan T-antigen is a common feature of human cancer cells that correlates with
metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages
is involved in their developmentally programmed tissue invasion. Higher macrophage
T-antigen levels require an atypical major facilitator superfamily (MFS) member
that we named Minerva which enables macrophage dissemination and invasion. We
characterize for the first time the T and Tn glycoform O-glycoproteome of the
Drosophila melanogaster embryo, and determine that Minerva increases the presence
of T-antigen on proteins in pathways previously linked to cancer, most strongly
on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue
entry. Minerva’s vertebrate ortholog, MFSD1, rescues the minerva mutant’s migration
and T-antigen glycosylation defects. We thus identify \r\na key conserved regulator
that orchestrates O-glycosylation on a protein subset to activate \r\na program
governing migration steps important for both development and cancer metastasis.
\r\n"
acknowledged_ssus:
- _id: Bio
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Katarina
full_name: Valosková, Katarina
id: 46F146FC-F248-11E8-B48F-1D18A9856A87
last_name: Valosková
citation:
ama: Valosková K. The role of a highly conserved major facilitator superfamily member
in Drosophila embryonic macrophage migration. 2019. doi:10.15479/AT:ISTA:6546
apa: Valosková, K. (2019). The role of a highly conserved major facilitator superfamily
member in Drosophila embryonic macrophage migration. Institute of Science
and Technology Austria. https://doi.org/10.15479/AT:ISTA:6546
chicago: Valosková, Katarina. “The Role of a Highly Conserved Major Facilitator
Superfamily Member in Drosophila Embryonic Macrophage Migration.” Institute of
Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6546.
ieee: K. Valosková, “The role of a highly conserved major facilitator superfamily
member in Drosophila embryonic macrophage migration,” Institute of Science and
Technology Austria, 2019.
ista: Valosková K. 2019. The role of a highly conserved major facilitator superfamily
member in Drosophila embryonic macrophage migration. Institute of Science and
Technology Austria.
mla: Valosková, Katarina. The Role of a Highly Conserved Major Facilitator Superfamily
Member in Drosophila Embryonic Macrophage Migration. Institute of Science
and Technology Austria, 2019, doi:10.15479/AT:ISTA:6546.
short: K. Valosková, The Role of a Highly Conserved Major Facilitator Superfamily
Member in Drosophila Embryonic Macrophage Migration, Institute of Science and
Technology Austria, 2019.
date_created: 2019-06-07T12:49:19Z
date_published: 2019-06-07T00:00:00Z
date_updated: 2023-09-19T10:15:54Z
day: '07'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: DaSi
doi: 10.15479/AT:ISTA:6546
file:
- access_level: closed
checksum: 68949c2d96210b45b981a23e9c9cd93c
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language:
- iso: eng
month: '06'
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page: '141'
project:
- _id: 253CDE40-B435-11E9-9278-68D0E5697425
grant_number: '24283'
name: Examination of the role of a MFS transporter in the migration of Drosophila
immune cells
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '6187'
relation: part_of_dissertation
status: public
- id: '544'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Daria E
full_name: Siekhaus, Daria E
id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
last_name: Siekhaus
orcid: 0000-0001-8323-8353
title: The role of a highly conserved major facilitator superfamily member in Drosophila
embryonic macrophage migration
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2019'
...
---
_id: '6363'
abstract:
- lang: eng
text: "Distinguishing between similar experiences is achieved by the brain
\ in a process called pattern separation. In the hippocampus, pattern
\ separation reduces the interference of memories and increases the storage
capacity by decorrelating similar inputs patterns of neuronal activity into
\ non-overlapping output firing patterns. Winners-take-all (WTA) mechanism
\ is a theoretical model for pattern separation in which a \"winner\"
\ cell suppresses the activity of the neighboring neurons through feedback
inhibition. However, if the network properties of the dentate gyrus support WTA
as a biologically conceivable model remains unknown. Here, we showed that the
connectivity rules of PV+interneurons and their synaptic properties are optimizedfor
efficient pattern separation. We found using multiple whole-cell in vitrorecordings
that PV+interneurons mainly connect to granule cells (GC) through lateral inhibition,
a form of feedback inhibition in which a GC inhibits other GCs but not
\ itself through the activation of PV+interneurons. Thus, lateral inhibition
between GC–PV+interneurons was ~10 times more abundant than recurrent connections.
Furthermore, the GC–PV+interneuron connectivity was more spatially confined
\ but less abundant than PV+interneurons–GC connectivity, leading to an
\ asymmetrical distribution of excitatory and inhibitory connectivity. Our
network model of the dentate gyrus with incorporated real connectivity rules efficiently
decorrelates neuronal activity patterns using WTA as the primary mechanism.
\ This process relied on lateral inhibition, fast-signaling properties of
\ PV+interneurons and the asymmetrical distribution of excitatory and inhibitory
connectivity. Finally, we found that silencing the activity of PV+interneurons
in vivoleads to acute deficits in discrimination between similar environments,
suggesting that PV+interneuron networks are necessary for behavioral relevant
computations. Our results demonstrate that PV+interneurons possess unique
connectivity and fast signaling properties that confer to the dentate
\ gyrus network properties that allow the emergence of pattern separation. Thus,
our results contribute to the knowledge of how specific forms of network organization
underlie sophisticated types of information processing. \r\n"
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: 'Claudia '
full_name: 'Espinoza Martinez, Claudia '
id: 31FFEE2E-F248-11E8-B48F-1D18A9856A87
last_name: Espinoza Martinez
orcid: 0000-0003-4710-2082
citation:
ama: Espinoza Martinez C. Parvalbumin+ interneurons enable efficient pattern separation
in hippocampal microcircuits. 2019. doi:10.15479/AT:ISTA:6363
apa: Espinoza Martinez, C. (2019). Parvalbumin+ interneurons enable efficient
pattern separation in hippocampal microcircuits. Institute of Science and
Technology Austria. https://doi.org/10.15479/AT:ISTA:6363
chicago: Espinoza Martinez, Claudia . “Parvalbumin+ Interneurons Enable Efficient
Pattern Separation in Hippocampal Microcircuits.” Institute of Science and Technology
Austria, 2019. https://doi.org/10.15479/AT:ISTA:6363.
ieee: C. Espinoza Martinez, “Parvalbumin+ interneurons enable efficient pattern
separation in hippocampal microcircuits,” Institute of Science and Technology
Austria, 2019.
ista: Espinoza Martinez C. 2019. Parvalbumin+ interneurons enable efficient pattern
separation in hippocampal microcircuits. Institute of Science and Technology Austria.
mla: Espinoza Martinez, Claudia. Parvalbumin+ Interneurons Enable Efficient Pattern
Separation in Hippocampal Microcircuits. Institute of Science and Technology
Austria, 2019, doi:10.15479/AT:ISTA:6363.
short: C. Espinoza Martinez, Parvalbumin+ Interneurons Enable Efficient Pattern
Separation in Hippocampal Microcircuits, Institute of Science and Technology Austria,
2019.
date_created: 2019-04-30T11:56:10Z
date_published: 2019-04-30T00:00:00Z
date_updated: 2023-09-15T12:03:48Z
day: '30'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: PeJo
doi: 10.15479/AT:ISTA:6363
file:
- access_level: open_access
checksum: 77c6c05cfe8b58c8abcf1b854375d084
content_type: application/pdf
creator: cespinoza
date_created: 2019-05-07T16:00:39Z
date_updated: 2021-02-11T11:17:15Z
embargo: 2020-05-09
file_id: '6389'
file_name: Espinozathesis_all2.pdf
file_size: 13966891
relation: main_file
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date_created: 2019-05-07T16:00:48Z
date_updated: 2020-07-14T12:47:28Z
embargo_to: open_access
file_id: '6390'
file_name: Espinoza_Thesis.docx
file_size: 11159900
relation: source_file
file_date_updated: 2021-02-11T11:17:15Z
has_accepted_license: '1'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: '140'
publication_identifier:
isbn:
- 978-3-99078-000-8
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '21'
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: Parvalbumin+ interneurons enable efficient pattern separation in hippocampal
microcircuits
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2019'
...