Summary: Researchers have been able to erase unpleasant memories in mice by using a ‘genetic switch, a new study reports.
Source: KU Leuven.
Researchers from KU Leuven and the Leibniz Institute for Neurobiology have managed to erase unpleasant memories in mice using a ‘genetic switch’. Their findings were published in Biological Psychiatry.
Dementia, accidents, or traumatic events can make us lose the memories formed before the injury or the onset of the disease. Researchers from KU Leuven and the Leibniz Institute for Neurobiology have now shown that some memories can also be erased when one particular gene is switched off.
The team trained mice that had been genetically modified in one single gene: neuroplastin. This gene, which is investigated by only a few groups in the world, is very important for brain plasticity. In humans, changes in the regulation of the neuroplastin gene have recently been linked to decreased intellectual abilities and schizophrenia.
In the reported study, the mice were trained to move from one side of a box to the other as soon as a lamp lights up, thus avoiding a foot stimulus. This learning process is called associative learning. Its most famous example is Pavlov’s dog: conditioned to associate the sound of a bell with getting food, the dog starts salivating whenever it hears a bell.
When the scientists switched off the neuroplastin gene after conditioning, the mice were no longer able to perform the task properly. In other words, they showed learning and memory deficits that were specifically related to associative learning. The control mice with the neuroplastin gene switched on, by contrast, could still do the task perfectly.
Professor Detlef Balschun from the KU Leuven Laboratory for Biological Psychology: “We were amazed to find that deactivating one single gene is enough to erase associative memories formed before or during the learning trials. Switching off the neuroplastin gene has an impact on the behaviour of the mice, because it interferes with the communication between their brain cells.”
By measuring the electrical signals in the brain, the KU Leuven team discovered clear deficits in the cellular mechanism used to store memories. These changes are even visible at the level of individual brain cells, as postdoctoral researcher Victor Sabanov was able to show.
“This is still basic research,” Balschun adds. “We still need further research to show whether neuroplastin also plays a role in other forms of learning.”
Source: Katrien Bollen – KU Leuven
Image Source: This NeuroscienceNews.com image is adapted from the KU Leuven press release.
Original Research: Full open access research for “Genetically Induced Retrograde Amnesia of Associative Memories After Neuroplastin Ablation” by 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, and Dirk Montag in Biological Psychiatry. Published online April 11 2016 doi:10.1016/j.biopsych.2016.03.2107
Genetically Induced Retrograde Amnesia of Associative Memories After Neuroplastin Ablation
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.
We characterized behavioral and functional changes in inducible conditional neuroplastin-deficient mice.
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.
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.
“Genetically Induced Retrograde Amnesia of Associative Memories After Neuroplastin Ablation” by 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, and Dirk Montag in Biological Psychiatry. Published online April 11 2016 doi:10.1016/j.biopsych.2016.03.2107