Abstract
Background Neuroplastin cell recognition molecules have been implicated in synaptic plasticity. Polymorphisms in the regulatory region of the human neuroplastin gene (NPTN) are correlated with cortical thickness and intellectual abilities in adolescents and in individuals with schizophrenia. Methods We characterized behavioral and functional changes in inducible conditional neuroplastin-deficient mice. Results We demonstrate that neuroplastins are required for associative learning in conditioning paradigms, e.g., two-way active avoidance and fear conditioning. Retrograde amnesia of learned associative memories is elicited by inducible neuron-specific ablation of Nptn gene expression in adult mice, which shows that neuroplastins are indispensable for the availability of previously acquired associative memories. Using single-photon emission computed tomography imaging in awake mice, we identified brain structures activated during memory recall. Constitutive neuroplastin deficiency or Nptn gene ablation in adult mice causes substantial electrophysiologic deficits such as reduced long-term potentiation. In addition, neuroplastin-deficient mice reveal profound physiologic and behavioral deficits, some of which are related to depression and schizophrenia, which illustrate neuroplastin's essential functions. Conclusions Neuroplastins are essential for learning and memory. Retrograde amnesia after an associative learning task can be induced by ablation of the neuroplastin gene. The inducible neuroplastin-deficient mouse model provides a new and unique means to analyze the molecular and cellular mechanisms underlying retrograde amnesia and memory.
| Original language | English |
|---|---|
| Pages (from-to) | 124-135 |
| Number of pages | 12 |
| Journal | Biological Psychiatry |
| Volume | 81 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 15 Jan 2017 |
| Externally published | Yes |
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Keywords
- Associative memory
- Knockout mouse model
- Learning impairment
- Neuroplastin
- Retrograde amnesia
- Synaptic plasticity
ASJC Scopus subject areas
- Biological Psychiatry
Cite this
Genetically Induced Retrograde Amnesia of Associative Memories After Neuroplastin Ablation. / Bhattacharya, Soumee; Herrera-Molina, Rodrigo; Sabanov, Victor; Ahmed, Tariq; Iscru, Emilia; Stöber, Franziska; Richter, Karin; Fischer, Klaus Dieter; Angenstein, Frank; Goldschmidt, Jürgen; Beesley, Philip W.; Balschun, Detlef; Smalla, Karl Heinz; Gundelfinger, Eckart D.; Montag, Dirk.
In: Biological Psychiatry, Vol. 81, No. 2, 15.01.2017, p. 124-135.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genetically Induced Retrograde Amnesia of Associative Memories After Neuroplastin Ablation
AU - Bhattacharya, Soumee
AU - Herrera-Molina, Rodrigo
AU - Sabanov, Victor
AU - Ahmed, Tariq
AU - Iscru, Emilia
AU - Stöber, Franziska
AU - Richter, Karin
AU - Fischer, Klaus Dieter
AU - Angenstein, Frank
AU - Goldschmidt, Jürgen
AU - Beesley, Philip W.
AU - Balschun, Detlef
AU - Smalla, Karl Heinz
AU - Gundelfinger, Eckart D.
AU - Montag, Dirk
PY - 2017/1/15
Y1 - 2017/1/15
N2 - Background Neuroplastin cell recognition molecules have been implicated in synaptic plasticity. Polymorphisms in the regulatory region of the human neuroplastin gene (NPTN) are correlated with cortical thickness and intellectual abilities in adolescents and in individuals with schizophrenia. Methods We characterized behavioral and functional changes in inducible conditional neuroplastin-deficient mice. Results We demonstrate that neuroplastins are required for associative learning in conditioning paradigms, e.g., two-way active avoidance and fear conditioning. Retrograde amnesia of learned associative memories is elicited by inducible neuron-specific ablation of Nptn gene expression in adult mice, which shows that neuroplastins are indispensable for the availability of previously acquired associative memories. Using single-photon emission computed tomography imaging in awake mice, we identified brain structures activated during memory recall. Constitutive neuroplastin deficiency or Nptn gene ablation in adult mice causes substantial electrophysiologic deficits such as reduced long-term potentiation. In addition, neuroplastin-deficient mice reveal profound physiologic and behavioral deficits, some of which are related to depression and schizophrenia, which illustrate neuroplastin's essential functions. Conclusions Neuroplastins are essential for learning and memory. Retrograde amnesia after an associative learning task can be induced by ablation of the neuroplastin gene. The inducible neuroplastin-deficient mouse model provides a new and unique means to analyze the molecular and cellular mechanisms underlying retrograde amnesia and memory.
AB - Background Neuroplastin cell recognition molecules have been implicated in synaptic plasticity. Polymorphisms in the regulatory region of the human neuroplastin gene (NPTN) are correlated with cortical thickness and intellectual abilities in adolescents and in individuals with schizophrenia. Methods We characterized behavioral and functional changes in inducible conditional neuroplastin-deficient mice. Results We demonstrate that neuroplastins are required for associative learning in conditioning paradigms, e.g., two-way active avoidance and fear conditioning. Retrograde amnesia of learned associative memories is elicited by inducible neuron-specific ablation of Nptn gene expression in adult mice, which shows that neuroplastins are indispensable for the availability of previously acquired associative memories. Using single-photon emission computed tomography imaging in awake mice, we identified brain structures activated during memory recall. Constitutive neuroplastin deficiency or Nptn gene ablation in adult mice causes substantial electrophysiologic deficits such as reduced long-term potentiation. In addition, neuroplastin-deficient mice reveal profound physiologic and behavioral deficits, some of which are related to depression and schizophrenia, which illustrate neuroplastin's essential functions. Conclusions Neuroplastins are essential for learning and memory. Retrograde amnesia after an associative learning task can be induced by ablation of the neuroplastin gene. The inducible neuroplastin-deficient mouse model provides a new and unique means to analyze the molecular and cellular mechanisms underlying retrograde amnesia and memory.
KW - Associative memory
KW - Knockout mouse model
KW - Learning impairment
KW - Neuroplastin
KW - Retrograde amnesia
KW - Synaptic plasticity
UR - http://www.scopus.com/inward/record.url?scp=84969577617&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84969577617&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2016.03.2107
DO - 10.1016/j.biopsych.2016.03.2107
M3 - Article
C2 - 27215477
AN - SCOPUS:84969577617
VL - 81
SP - 124
EP - 135
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
IS - 2
ER -