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A mouse model of th...
A mouse model of the 15q13.3 microdeletion syndrome shows prefrontal neurophysiological dysfunctions and attentional impairment
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- Nilsson, Simon R O (författare)
- The State University of New York,University of Cambridge
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- Celada, Pau (författare)
- CIBER Salud Mental (CIBERSAM)
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- Fejgin, Kim (författare)
- H. Lundbeck A/S
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- Thelin, Jonas (författare)
- Lund University,Lunds universitet,Neuronano Research Center (NRC),Forskargrupper vid Lunds universitet,Lund University Research Groups,H. Lundbeck A/S
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- Nielsen, Jacob (författare)
- H. Lundbeck A/S
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- Santana, Noemí (författare)
- CIBER Salud Mental (CIBERSAM)
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- Heath, Christopher J. (författare)
- Open University
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- Larsen, Peter H. (författare)
- H. Lundbeck A/S
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- Nielsen, Vibeke (författare)
- H. Lundbeck A/S
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- Kent, Brianne A. (författare)
- University of Cambridge
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- Saksida, Lisa M. (författare)
- University of Cambridge
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- Stensbøl, Tine B. (författare)
- H. Lundbeck A/S
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- Robbins, Trevor W. (författare)
- University of Cambridge
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- Bastlund, Jesper F. (författare)
- H. Lundbeck A/S
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- Bussey, Timothy J. (författare)
- University of Cambridge
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- Artigas, Francesc (författare)
- CIBER Salud Mental (CIBERSAM)
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- Didriksen, Michael (författare)
- H. Lundbeck A/S
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(creator_code:org_t)
- 2016-03-17
- 2016
- Engelska 13 s.
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Ingår i: Psychopharmacologia. - : Springer Science and Business Media LLC. - 0033-3158. ; 233:11, s. 2151-2163
- Relaterad länk:
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http://dx.doi.org/10...
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https://link.springe...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Rationale: A microdeletion at locus 15q13.3 is associated with high incidence rates of psychopathology, including schizophrenia. A mouse model of the 15q13.3 microdeletion syndrome has been generated (Df[h15q13]/+) with translational utility for modelling schizophrenia-like pathology. Among other deficits, schizophrenia is characterised by dysfunctions in prefrontal cortical (PFC) inhibitory circuitry and attention. Objectives: The objective of this study is to assess PFC-dependent functioning in the Df(h15q13)/+ mouse using electrophysiological, pharmacological, and behavioural assays. Method: Experiments 1–2 investigated baseline firing and auditory-evoked responses of PFC interneurons and pyramidal neurons. Experiment 3 measured pyramidal firing in response to intra-PFC GABAAreceptor antagonism. Experiments 4–6 assessed PFC-dependent attentional functioning through the touchscreen 5-choice serial reaction time task (5-CSRTT). Experiments 7–12 assessed reversal learning, paired-associate learning, extinction learning, progressive ratio, trial-unique non-match to sample, and object recognition. Results: In experiments 1–3, the Df(h15q13)/+ mouse showed reduced baseline firing rate of fast-spiking interneurons and in the ability of the GABAAreceptor antagonist gabazine to increase the firing rate of pyramidal neurons. In assays of auditory-evoked responses, PFC interneurons in the Df(h15q13)/+ mouse had reduced detection amplitudes and increased detection latencies, while pyramidal neurons showed increased detection latencies. In experiments 4–6, the Df(h15q13)/+ mouse showed a stimulus duration-dependent decrease in percent accuracy in the 5-CSRTT. The impairment was insensitive to treatment with the partial α7nAChR agonist EVP-6124. The Df(h15q13)/+ mouse showed no cognitive impairments in experiments 7–12. Conclusion: The Df(h15q13)/+ mouse has multiple dysfunctions converging on disrupted PFC processing as measured by several independent assays of inhibitory transmission and attentional function.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- 15q13.3
- Animal model
- Chrna7
- Cognition
- Copy number variation
- Neurophysiology
- Prefrontal cortex
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Nilsson, Simon R ...
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Celada, Pau
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Fejgin, Kim
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Thelin, Jonas
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Nielsen, Jacob
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Santana, Noemí
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visa fler...
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Heath, Christoph ...
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Larsen, Peter H.
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Nielsen, Vibeke
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Kent, Brianne A.
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Saksida, Lisa M.
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Stensbøl, Tine B ...
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Robbins, Trevor ...
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Bastlund, Jesper ...
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Bussey, Timothy ...
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Artigas, Frances ...
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Didriksen, Micha ...
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Lunds universitet