Genetically Induced Retrograde Amnesia of Associative Memories After Neuroplastin Ablation

Soumee Bhattacharya, Rodrigo Herrera-Molina, Victor Sabanov, Tariq Ahmed, Emilia Iscru, Franziska Stöber, Karin Richter, Klaus Dieter Fischer, Frank Angenstein, Jürgen Goldschmidt, Philip W. Beesley, Detlef Balschun, Karl Heinz Smalla, Eckart D. Gundelfinger, Dirk Montag

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13 Citations (Scopus)


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 languageEnglish
Pages (from-to)124-135
Number of pages12
JournalBiological Psychiatry
Issue number2
Publication statusPublished - 15 Jan 2017
Externally publishedYes



  • Associative memory
  • Knockout mouse model
  • Learning impairment
  • Neuroplastin
  • Retrograde amnesia
  • Synaptic plasticity

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Bhattacharya, S., Herrera-Molina, R., Sabanov, V., Ahmed, T., Iscru, E., Stöber, F., Richter, K., Fischer, K. D., Angenstein, F., Goldschmidt, J., Beesley, P. W., Balschun, D., Smalla, K. H., Gundelfinger, E. D., & Montag, D. (2017). Genetically Induced Retrograde Amnesia of Associative Memories After Neuroplastin Ablation. Biological Psychiatry, 81(2), 124-135.