---
_id: '14314'
abstract:
- lang: eng
  text: The execution of cognitive functions requires coordinated circuit activity
    across different brain areas that involves the associated firing of neuronal assemblies.
    Here, we tested the circuit mechanism behind assembly interactions between the
    hippocampus and the medial prefrontal cortex (mPFC) of adult rats by recording
    neuronal populations during a rule-switching task. We identified functionally
    coupled CA1-mPFC cells that synchronized their activity beyond that expected from
    common spatial coding or oscillatory firing. When such cell pairs fired together,
    the mPFC cell strongly phase locked to CA1 theta oscillations and maintained consistent
    theta firing phases, independent of the theta timing of their CA1 counterpart.
    These functionally connected CA1-mPFC cells formed interconnected assemblies.
    While firing together with their CA1 assembly partners, mPFC cells fired along
    specific theta sequences. Our results suggest that upregulated theta oscillatory
    firing of mPFC cells can signal transient interactions with specific CA1 assemblies,
    thus enabling distributed computations.
acknowledgement: We thank A. Cumpelik, H. Chiossi, and L. Bollman for comments on
  an earlier version of this manuscript. This work was funded by EU-FP7 MC-ITN IN-SENS
  (grant 607616).
article_number: '113015'
article_processing_charge: Yes
article_type: original
author:
- first_name: Michele
  full_name: Nardin, Michele
  id: 30BD0376-F248-11E8-B48F-1D18A9856A87
  last_name: Nardin
  orcid: 0000-0001-8849-6570
- first_name: Karola
  full_name: Käfer, Karola
  id: 2DAA49AA-F248-11E8-B48F-1D18A9856A87
  last_name: Käfer
- first_name: Federico
  full_name: Stella, Federico
  id: 39AF1E74-F248-11E8-B48F-1D18A9856A87
  last_name: Stella
  orcid: 0000-0001-9439-3148
- 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: Nardin M, Käfer K, Stella F, Csicsvari JL. Theta oscillations as a substrate
    for medial prefrontal-hippocampal assembly interactions. <i>Cell Reports</i>.
    2023;42(9). doi:<a href="https://doi.org/10.1016/j.celrep.2023.113015">10.1016/j.celrep.2023.113015</a>
  apa: Nardin, M., Käfer, K., Stella, F., &#38; Csicsvari, J. L. (2023). Theta oscillations
    as a substrate for medial prefrontal-hippocampal assembly interactions. <i>Cell
    Reports</i>. Elsevier. <a href="https://doi.org/10.1016/j.celrep.2023.113015">https://doi.org/10.1016/j.celrep.2023.113015</a>
  chicago: Nardin, Michele, Karola Käfer, Federico Stella, and Jozsef L Csicsvari.
    “Theta Oscillations as a Substrate for Medial Prefrontal-Hippocampal Assembly
    Interactions.” <i>Cell Reports</i>. Elsevier, 2023. <a href="https://doi.org/10.1016/j.celrep.2023.113015">https://doi.org/10.1016/j.celrep.2023.113015</a>.
  ieee: M. Nardin, K. Käfer, F. Stella, and J. L. Csicsvari, “Theta oscillations as
    a substrate for medial prefrontal-hippocampal assembly interactions,” <i>Cell
    Reports</i>, vol. 42, no. 9. Elsevier, 2023.
  ista: Nardin M, Käfer K, Stella F, Csicsvari JL. 2023. Theta oscillations as a substrate
    for medial prefrontal-hippocampal assembly interactions. Cell Reports. 42(9),
    113015.
  mla: Nardin, Michele, et al. “Theta Oscillations as a Substrate for Medial Prefrontal-Hippocampal
    Assembly Interactions.” <i>Cell Reports</i>, vol. 42, no. 9, 113015, Elsevier,
    2023, doi:<a href="https://doi.org/10.1016/j.celrep.2023.113015">10.1016/j.celrep.2023.113015</a>.
  short: M. Nardin, K. Käfer, F. Stella, J.L. Csicsvari, Cell Reports 42 (2023).
date_created: 2023-09-10T22:01:11Z
date_published: 2023-09-26T00:00:00Z
date_updated: 2023-09-15T07:14:12Z
day: '26'
ddc:
- '570'
department:
- _id: JoCs
doi: 10.1016/j.celrep.2023.113015
ec_funded: 1
external_id:
  pmid:
  - '37632747'
file:
- access_level: open_access
  checksum: ca77a304fb813c292550b8604b0fb41d
  content_type: application/pdf
  creator: dernst
  date_created: 2023-09-15T07:12:46Z
  date_updated: 2023-09-15T07:12:46Z
  file_id: '14337'
  file_name: 2023_CellPress_Nardin.pdf
  file_size: 4879455
  relation: main_file
  success: 1
file_date_updated: 2023-09-15T07:12:46Z
has_accepted_license: '1'
intvolume: '        42'
issue: '9'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 257BBB4C-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '607616'
  name: Inter-and intracellular signalling in schizophrenia
publication: Cell Reports
publication_identifier:
  eissn:
  - 2211-1247
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Theta oscillations as a substrate for medial prefrontal-hippocampal assembly
  interactions
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: 42
year: '2023'
...
---
_id: '11951'
abstract:
- lang: eng
  text: The mammalian hippocampal formation (HF) plays a key role in several higher
    brain functions, such as spatial coding, learning and memory. Its simple circuit
    architecture is often viewed as a trisynaptic loop, processing input originating
    from the superficial layers of the entorhinal cortex (EC) and sending it back
    to its deeper layers. Here, we show that excitatory neurons in layer 6b of the
    mouse EC project to all sub-regions comprising the HF and receive input from the
    CA1, thalamus and claustrum. Furthermore, their output is characterized by unique
    slow-decaying excitatory postsynaptic currents capable of driving plateau-like
    potentials in their postsynaptic targets. Optogenetic inhibition of the EC-6b
    pathway affects spatial coding in CA1 pyramidal neurons, while cell ablation impairs
    not only acquisition of new spatial memories, but also degradation of previously
    acquired ones. Our results provide evidence of a functional role for cortical
    layer 6b neurons in the adult brain.
acknowledged_ssus:
- _id: Bio
- _id: SSU
acknowledgement: We thank F. Marr and A. Schlögl for technical assistance, E. Kralli-Beller
  for manuscript editing, as well as C. Sommer and the Imaging and Optics Facility
  of the Institute of Science and Technology Austria (ISTA) for image analysis scripts
  and microscopy support. We extend our gratitude to J. Wallenschus and D. Rangel
  Guerrero for technical assistance acquiring single-unit data and I. Gridchyn for
  help with single-unit clustering. Finally, we also thank B. Suter for discussions,
  A. Saunders, M. Jösch, and H. Monyer for critically reading earlier versions of
  the manuscript, C. Petersen for sharing clearing protocols, and the Scientific Service
  Units of ISTA for efficient support. This project was funded by the European Research
  Council (ERC) under the European Union’s Horizon 2020 research and innovation programme
  (ERC advanced grant No 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen
  Forschung (Z 312-B27, Wittgenstein award for P.J. and I3600-B27 for J.G.D. and P.V.).
article_number: '4826'
article_processing_charge: No
article_type: original
author:
- first_name: Yoav
  full_name: Ben Simon, Yoav
  id: 43DF3136-F248-11E8-B48F-1D18A9856A87
  last_name: Ben Simon
- first_name: Karola
  full_name: Käfer, Karola
  id: 2DAA49AA-F248-11E8-B48F-1D18A9856A87
  last_name: Käfer
- first_name: Philipp
  full_name: Velicky, Philipp
  id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
  last_name: Velicky
  orcid: 0000-0002-2340-7431
- first_name: Jozsef L
  full_name: Csicsvari, Jozsef L
  id: 3FA14672-F248-11E8-B48F-1D18A9856A87
  last_name: Csicsvari
  orcid: 0000-0002-5193-4036
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
- 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: Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. A direct
    excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes
    to spatial coding and memory. <i>Nature Communications</i>. 2022;13. doi:<a href="https://doi.org/10.1038/s41467-022-32559-8">10.1038/s41467-022-32559-8</a>
  apa: Ben Simon, Y., Käfer, K., Velicky, P., Csicsvari, J. L., Danzl, J. G., &#38;
    Jonas, P. M. (2022). A direct excitatory projection from entorhinal layer 6b neurons
    to the hippocampus contributes to spatial coding and memory. <i>Nature Communications</i>.
    Springer Nature. <a href="https://doi.org/10.1038/s41467-022-32559-8">https://doi.org/10.1038/s41467-022-32559-8</a>
  chicago: Ben Simon, Yoav, Karola Käfer, Philipp Velicky, Jozsef L Csicsvari, Johann
    G Danzl, and Peter M Jonas. “A Direct Excitatory Projection from Entorhinal Layer
    6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” <i>Nature
    Communications</i>. Springer Nature, 2022. <a href="https://doi.org/10.1038/s41467-022-32559-8">https://doi.org/10.1038/s41467-022-32559-8</a>.
  ieee: Y. Ben Simon, K. Käfer, P. Velicky, J. L. Csicsvari, J. G. Danzl, and P. M.
    Jonas, “A direct excitatory projection from entorhinal layer 6b neurons to the
    hippocampus contributes to spatial coding and memory,” <i>Nature Communications</i>,
    vol. 13. Springer Nature, 2022.
  ista: Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. 2022. A
    direct excitatory projection from entorhinal layer 6b neurons to the hippocampus
    contributes to spatial coding and memory. Nature Communications. 13, 4826.
  mla: Ben Simon, Yoav, et al. “A Direct Excitatory Projection from Entorhinal Layer
    6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” <i>Nature
    Communications</i>, vol. 13, 4826, Springer Nature, 2022, doi:<a href="https://doi.org/10.1038/s41467-022-32559-8">10.1038/s41467-022-32559-8</a>.
  short: Y. Ben Simon, K. Käfer, P. Velicky, J.L. Csicsvari, J.G. Danzl, P.M. Jonas,
    Nature Communications 13 (2022).
date_created: 2022-08-24T08:25:50Z
date_published: 2022-08-16T00:00:00Z
date_updated: 2023-08-03T13:01:19Z
day: '16'
ddc:
- '570'
department:
- _id: JoCs
- _id: PeJo
- _id: JoDa
doi: 10.1038/s41467-022-32559-8
ec_funded: 1
external_id:
  isi:
  - '000841396400008'
file:
- access_level: open_access
  checksum: 405936d9e4d33625d80c093c9713a91f
  content_type: application/pdf
  creator: dernst
  date_created: 2022-08-26T11:51:40Z
  date_updated: 2022-08-26T11:51:40Z
  file_id: '11990'
  file_name: 2022_NatureCommunications_BenSimon.pdf
  file_size: 5910357
  relation: main_file
  success: 1
file_date_updated: 2022-08-26T11:51:40Z
has_accepted_license: '1'
intvolume: '        13'
isi: 1
keyword:
- General Physics and Astronomy
- General Biochemistry
- Genetics and Molecular Biology
- General Chemistry
- Multidisciplinary
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I03600
  name: Optical control of synaptic function via adhesion molecules
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: The Wittgenstein Prize
publication: Nature Communications
publication_identifier:
  issn:
  - 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
status: public
title: A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus
  contributes to spatial coding and memory
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: 13
year: '2022'
...
---
_id: '10080'
abstract:
- lang: eng
  text: Hippocampal and neocortical neural activity is modulated by the position of
    the individual in space. While hippocampal neurons provide the basis for a spatial
    map, prefrontal cortical neurons generalize over environmental features. Whether
    these generalized representations result from a bidirectional interaction with,
    or are mainly derived from hippocampal spatial representations is not known. By
    examining simultaneously recorded hippocampal and medial prefrontal neurons, we
    observed that prefrontal spatial representations show a delayed coherence with
    hippocampal ones. We also identified subpopulations of cells in the hippocampus
    and medial prefrontal cortex that formed functional cross-area couplings; these
    resembled the optimal connections predicted by a probabilistic model of spatial
    information transfer and generalization. Moreover, cross-area couplings were strongest
    and had the shortest delay preceding spatial decision-making. Our results suggest
    that generalized spatial coding in the medial prefrontal cortex is inherited from
    spatial representations in the hippocampus, and that the routing of information
    can change dynamically with behavioral demands.
acknowledgement: We thank Federico Stella for invaluable suggestions and discussions.
  We thank Yosman BapatDhar and Andrea Cumpelik for comments, help and suggestions
  on the exposure of the text. We thank Predrag Živadinović and Juliana Couras for
  comments on the text and the figures. This work was supported by the EU-FP7 MC-ITN
  IN-SENS (grant 607616).
article_processing_charge: No
author:
- first_name: Michele
  full_name: Nardin, Michele
  id: 30BD0376-F248-11E8-B48F-1D18A9856A87
  last_name: Nardin
  orcid: 0000-0001-8849-6570
- first_name: Karola
  full_name: Käfer, Karola
  id: 2DAA49AA-F248-11E8-B48F-1D18A9856A87
  last_name: Käfer
- 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: Nardin M, Käfer K, Csicsvari JL. The generalized spatial representation in
    the prefrontal cortex is inherited from the hippocampus. <i>bioRxiv</i>. doi:<a
    href="https://doi.org/10.1101/2021.09.30.462269">10.1101/2021.09.30.462269</a>
  apa: Nardin, M., Käfer, K., &#38; Csicsvari, J. L. (n.d.). The generalized spatial
    representation in the prefrontal cortex is inherited from the hippocampus. <i>bioRxiv</i>.
    Cold Spring Harbor Laboratory. <a href="https://doi.org/10.1101/2021.09.30.462269">https://doi.org/10.1101/2021.09.30.462269</a>
  chicago: Nardin, Michele, Karola Käfer, and Jozsef L Csicsvari. “The Generalized
    Spatial Representation in the Prefrontal Cortex Is Inherited from the Hippocampus.”
    <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href="https://doi.org/10.1101/2021.09.30.462269">https://doi.org/10.1101/2021.09.30.462269</a>.
  ieee: M. Nardin, K. Käfer, and J. L. Csicsvari, “The generalized spatial representation
    in the prefrontal cortex is inherited from the hippocampus,” <i>bioRxiv</i>. Cold
    Spring Harbor Laboratory.
  ista: Nardin M, Käfer K, Csicsvari JL. The generalized spatial representation in
    the prefrontal cortex is inherited from the hippocampus. bioRxiv, <a href="https://doi.org/10.1101/2021.09.30.462269">10.1101/2021.09.30.462269</a>.
  mla: Nardin, Michele, et al. “The Generalized Spatial Representation in the Prefrontal
    Cortex Is Inherited from the Hippocampus.” <i>BioRxiv</i>, Cold Spring Harbor
    Laboratory, doi:<a href="https://doi.org/10.1101/2021.09.30.462269">10.1101/2021.09.30.462269</a>.
  short: M. Nardin, K. Käfer, J.L. Csicsvari, BioRxiv (n.d.).
date_created: 2021-10-04T06:28:32Z
date_published: 2021-10-02T00:00:00Z
date_updated: 2021-10-05T12:34:26Z
day: '02'
department:
- _id: GradSch
- _id: JoCs
doi: 10.1101/2021.09.30.462269
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.biorxiv.org/content/10.1101/2021.09.30.462269
month: '10'
oa: 1
oa_version: Preprint
project:
- _id: 257BBB4C-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '607616'
  name: Inter-and intracellular signalling in schizophrenia
publication: bioRxiv
publication_status: submitted
publisher: Cold Spring Harbor Laboratory
status: public
title: The generalized spatial representation in the prefrontal cortex is inherited
  from the hippocampus
type: preprint
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2021'
...
---
_id: '7472'
abstract:
- lang: eng
  text: Temporally organized reactivation of experiences during awake immobility periods
    is thought to underlie cognitive processes like planning and evaluation. While
    replay of trajectories is well established for the hippocampus, it is unclear
    whether the medial prefrontal cortex (mPFC) can reactivate sequential behavioral
    experiences in the awake state to support task execution. We simultaneously recorded
    from hippocampal and mPFC principal neurons in rats performing a mPFC-dependent
    rule-switching task on a plus maze. We found that mPFC neuronal activity encoded
    relative positions between the start and goal. During awake immobility periods,
    the mPFC replayed temporally organized sequences of these generalized positions,
    resembling entire spatial trajectories. The occurrence of mPFC trajectory replay
    positively correlated with rule-switching performance. However, hippocampal and
    mPFC trajectory replay occurred independently, indicating different functions.
    These results demonstrate that the mPFC can replay ordered activity patterns representing
    generalized locations and suggest that mPFC replay might have a role in flexible
    behavior.
acknowledged_ssus:
- _id: M-Shop
acknowledgement: We thank Todor Asenov and Thomas Menner from the Machine Shop for
  the drive design and production, Hugo Malagon-Vina for assistance in maze automatization,
  Jago Wallenschus for taking the images of the histology, and Federico Stella and
  Juan Felipe Ramirez-Villegas for comments on an earlier version of the manuscript.
  This work was supported by the EU-FP7 MC-ITN IN-SENS (grant 607616 ).
article_processing_charge: No
article_type: original
author:
- first_name: Karola
  full_name: Käfer, Karola
  id: 2DAA49AA-F248-11E8-B48F-1D18A9856A87
  last_name: Käfer
- first_name: Michele
  full_name: Nardin, Michele
  id: 30BD0376-F248-11E8-B48F-1D18A9856A87
  last_name: Nardin
  orcid: 0000-0001-8849-6570
- first_name: Karel
  full_name: Blahna, Karel
  id: 3EA859AE-F248-11E8-B48F-1D18A9856A87
  last_name: Blahna
- 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, Nardin M, Blahna K, Csicsvari JL. Replay of behavioral sequences in
    the medial prefrontal cortex during rule switching. <i>Neuron</i>. 2020;106(1):P154-165.e6.
    doi:<a href="https://doi.org/10.1016/j.neuron.2020.01.015">10.1016/j.neuron.2020.01.015</a>
  apa: Käfer, K., Nardin, M., Blahna, K., &#38; Csicsvari, J. L. (2020). Replay of
    behavioral sequences in the medial prefrontal cortex during rule switching. <i>Neuron</i>.
    Elsevier. <a href="https://doi.org/10.1016/j.neuron.2020.01.015">https://doi.org/10.1016/j.neuron.2020.01.015</a>
  chicago: Käfer, Karola, Michele Nardin, Karel Blahna, and Jozsef L Csicsvari. “Replay
    of Behavioral Sequences in the Medial Prefrontal Cortex during Rule Switching.”
    <i>Neuron</i>. Elsevier, 2020. <a href="https://doi.org/10.1016/j.neuron.2020.01.015">https://doi.org/10.1016/j.neuron.2020.01.015</a>.
  ieee: K. Käfer, M. Nardin, K. Blahna, and J. L. Csicsvari, “Replay of behavioral
    sequences in the medial prefrontal cortex during rule switching,” <i>Neuron</i>,
    vol. 106, no. 1. Elsevier, p. P154–165.e6, 2020.
  ista: Käfer K, Nardin M, Blahna K, Csicsvari JL. 2020. Replay of behavioral sequences
    in the medial prefrontal cortex during rule switching. Neuron. 106(1), P154–165.e6.
  mla: Käfer, Karola, et al. “Replay of Behavioral Sequences in the Medial Prefrontal
    Cortex during Rule Switching.” <i>Neuron</i>, vol. 106, no. 1, Elsevier, 2020,
    p. P154–165.e6, doi:<a href="https://doi.org/10.1016/j.neuron.2020.01.015">10.1016/j.neuron.2020.01.015</a>.
  short: K. Käfer, M. Nardin, K. Blahna, J.L. Csicsvari, Neuron 106 (2020) P154–165.e6.
date_created: 2020-02-10T15:45:48Z
date_published: 2020-04-08T00:00:00Z
date_updated: 2023-08-17T14:38:02Z
day: '08'
department:
- _id: JoCs
doi: 10.1016/j.neuron.2020.01.015
ec_funded: 1
external_id:
  isi:
  - '000525319300016'
  pmid:
  - '32032512'
intvolume: '       106'
isi: 1
issue: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1016/j.neuron.2020.01.015
month: '04'
oa: 1
oa_version: Published Version
page: P154-165.e6
pmid: 1
project:
- _id: 257BBB4C-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '607616'
  name: Inter-and intracellular signalling in schizophrenia
publication: Neuron
publication_identifier:
  issn:
  - 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/this-brain-area-helps-us-decide/
scopus_import: '1'
status: public
title: Replay of behavioral sequences in the medial prefrontal cortex during rule
  switching
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 106
year: '2020'
...
---
_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:<a href="https://doi.org/10.15479/AT:ISTA:6825">10.15479/AT:ISTA:6825</a>
  apa: Käfer, K. (2019). <i>The hippocampus and medial prefrontal cortex during flexible
    behavior</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:6825">https://doi.org/10.15479/AT:ISTA:6825</a>
  chicago: Käfer, Karola. “The Hippocampus and Medial Prefrontal Cortex during Flexible
    Behavior.” Institute of Science and Technology Austria, 2019. <a href="https://doi.org/10.15479/AT:ISTA:6825">https://doi.org/10.15479/AT:ISTA:6825</a>.
  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. <i>The Hippocampus and Medial Prefrontal Cortex during Flexible
    Behavior</i>. Institute of Science and Technology Austria, 2019, doi:<a href="https://doi.org/10.15479/AT:ISTA:6825">10.15479/AT:ISTA:6825</a>.
  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
day: '24'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: JoCs
doi: 10.15479/AT:ISTA:6825
file:
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file_date_updated: 2020-09-15T22:30:05Z
has_accepted_license: '1'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
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: '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. <i>Hippocampus</i>.
    2019;29(9):802-816. doi:<a href="https://doi.org/10.1002/hipo.23076">10.1002/hipo.23076</a>
  apa: Käfer, K., Malagon-Vina, H., Dickerson, D., O’Neill, J., Trossbach, S. V.,
    Korth, C., &#38; Csicsvari, J. L. (2019). Disrupted-in-schizophrenia 1 overexpression
    disrupts hippocampal coding and oscillatory synchronization. <i>Hippocampus</i>.
    Wiley. <a href="https://doi.org/10.1002/hipo.23076">https://doi.org/10.1002/hipo.23076</a>
  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.”
    <i>Hippocampus</i>. Wiley, 2019. <a href="https://doi.org/10.1002/hipo.23076">https://doi.org/10.1002/hipo.23076</a>.
  ieee: K. Käfer <i>et al.</i>, “Disrupted-in-schizophrenia 1 overexpression disrupts
    hippocampal coding and oscillatory synchronization,” <i>Hippocampus</i>, 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.” <i>Hippocampus</i>, vol.
    29, no. 9, Wiley, 2019, pp. 802–16, doi:<a href="https://doi.org/10.1002/hipo.23076">10.1002/hipo.23076</a>.
  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: 2024-03-25T23:30:11Z
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'
...
