---
_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: 2026-04-29T22:30:50Z
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: '476'
abstract:
- lang: eng
text: 'Maternal exposure to infection occurring mid-gestation produces a three-fold
increase in the risk of schizophrenia in the offspring. The critical initiating
factor appears to be the maternal immune activation (MIA) that follows infection.
This process can be induced in rodents by exposure of pregnant dams to the viral
mimic Poly I:C, which triggers an immune response that results in structural,
functional, behavioral, and electrophysiological phenotypes in the adult offspring
that model those seen in schizophrenia. We used this model to explore the role
of synchronization in brain neural networks, a process thought to be dysfunctional
in schizophrenia and previously associated with positive, negative, and cognitive
symptoms of schizophrenia. Exposure of pregnant dams to Poly I:C on GD15 produced
an impairment in long-range neural synchrony in adult offspring between two regions
implicated in schizophrenia pathology; the hippocampus and the medial prefrontal
cortex (mPFC). This reduction in synchrony was ameliorated by acute doses of the
antipsychotic clozapine. MIA animals have previously been shown to have impaired
pre-pulse inhibition (PPI), a gold-standard measure of schizophrenia-like deficits
in animal models. Our data showed that deficits in synchrony were positively correlated
with the impairments in PPI. Subsequent analysis of LFP activity during the PPI
response also showed that reduced coupling between the mPFC and the hippocampus
following processing of the pre-pulse was associated with reduced PPI. The ability
of the MIA intervention to model neurodevelopmental aspects of schizophrenia pathology
provides a useful platform from which to investigate the ontogeny of aberrant
synchronous processes. Further, the way in which the model expresses translatable
deficits such as aberrant synchrony and reduced PPI will allow researchers to
explore novel intervention strategies targeted to these changes. '
article_processing_charge: No
author:
- first_name: Desiree
full_name: Dickerson, Desiree
id: 444EB89E-F248-11E8-B48F-1D18A9856A87
last_name: Dickerson
- first_name: David
full_name: Bilkey, David
last_name: Bilkey
citation:
ama: 'Dickerson D, Bilkey D. Aberrant neural synchrony in the maternal immune activation
model: Using translatable measures to explore targeted interventions. Frontiers
in Behavioral Neuroscience. 2013;7(DEC). doi:10.3389/fnbeh.2013.00217'
apa: 'Dickerson, D., & Bilkey, D. (2013). Aberrant neural synchrony in the maternal
immune activation model: Using translatable measures to explore targeted interventions.
Frontiers in Behavioral Neuroscience. Frontiers Research Foundation. https://doi.org/10.3389/fnbeh.2013.00217'
chicago: 'Dickerson, Desiree, and David Bilkey. “Aberrant Neural Synchrony in the
Maternal Immune Activation Model: Using Translatable Measures to Explore Targeted
Interventions.” Frontiers in Behavioral Neuroscience. Frontiers Research
Foundation, 2013. https://doi.org/10.3389/fnbeh.2013.00217.'
ieee: 'D. Dickerson and D. Bilkey, “Aberrant neural synchrony in the maternal immune
activation model: Using translatable measures to explore targeted interventions,”
Frontiers in Behavioral Neuroscience, vol. 7, no. DEC. Frontiers Research
Foundation, 2013.'
ista: 'Dickerson D, Bilkey D. 2013. Aberrant neural synchrony in the maternal immune
activation model: Using translatable measures to explore targeted interventions.
Frontiers in Behavioral Neuroscience. 7(DEC).'
mla: 'Dickerson, Desiree, and David Bilkey. “Aberrant Neural Synchrony in the Maternal
Immune Activation Model: Using Translatable Measures to Explore Targeted Interventions.”
Frontiers in Behavioral Neuroscience, vol. 7, no. DEC, Frontiers Research
Foundation, 2013, doi:10.3389/fnbeh.2013.00217.'
short: D. Dickerson, D. Bilkey, Frontiers in Behavioral Neuroscience 7 (2013).
date_created: 2018-12-11T11:46:41Z
date_published: 2013-12-27T00:00:00Z
date_updated: 2025-09-30T07:30:04Z
day: '27'
ddc:
- '571'
department:
- _id: JoCs
doi: 10.3389/fnbeh.2013.00217
external_id:
isi:
- '000329175600001'
file:
- access_level: open_access
checksum: cd7183121e56251176100ccac165c95c
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:15:10Z
date_updated: 2020-07-14T12:46:35Z
file_id: '5128'
file_name: IST-2018-953-v1+1_2013_Dickerson_Aberrant_neural.pdf
file_size: 530134
relation: main_file
file_date_updated: 2020-07-14T12:46:35Z
has_accepted_license: '1'
intvolume: ' 7'
isi: 1
issue: DEC
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
publication: Frontiers in Behavioral Neuroscience
publication_status: published
publisher: Frontiers Research Foundation
publist_id: '7346'
pubrep_id: '953'
quality_controlled: '1'
status: public
title: 'Aberrant neural synchrony in the maternal immune activation model: Using translatable
measures to explore targeted interventions'
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 7
year: '2013'
...