Silencing Neuroplastin Gene Erases Pavlovian Memory

    Ringing the changes on Pavlovian memory, scientists based at KU Leuven dispensed with dogs and bells and food rewards and instead worked with mice and lamps and electric shocks. Most important, the scientists introduced gene silencing. This extra variation allowed them to demonstrate that silencing just one gene, the gene for neuroplastin, can erase a Pavlovian memory, a learned association.

    Thus far, other kinds of memory appear to be unaffected by the silencing of the neuroplastin gene. And so the KU Leuven scientists expressed optimism that neuroplastins may become an attractive therapeutic target. Tweaking the expression of the neuroplastin gene could effectively modulate memory after traumatic experiences and in posttraumatic stress disorder.

    This speculation appeared in the journal Biological Psychiatry, in an article entitled, “Genetically Induced Retrograde Amnesia of Associative Memories after Neuroplastin Ablation.” It describes how the KU Leuven scientists generated inducible neuroplastin-deficient mice and analyzed the dependence of learning and memory and synaptic plasticity on neuroplastins.

    “We demonstrate that neuroplastins are required for associative learning in conditioning paradigms, e.g., two-way active avoidance and fear conditioning,” wrote the article’s authors. “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.”

    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. By studying how the neuroplastin gene works in mice, the KU team hopes to identify specific loci for associative memories and disentangle molecular mechanisms underlying amnesia.

    “We were amazed to find that deactivating one single gene is enough to erase associative memories formed before or during the learning trials,” said Professor Detlef Balschun from the KU Leuven Laboratory for Biological Psychology. “Switching off the neuroplastin gene has an impact on the behavior 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.

    “Using single-photon emission computed tomography imaging in awake mice, we identified brain structures activated during memory recall,” the authors noted. “Constitutive neuroplastin deficiency orNptn gene ablation in adult mice causes substantial electrophysiologic deficits such as reduced long-term potentiation.”

    In addition, the authors indicated that neuroplastin-deficient mice reveal profound physiologic and behavioral deficits, some of which are related to depression and schizophrenia, which illustrate neuroplastin’s essential functions.

    “This is still basic research,” Professor Balschun concluded. “We still need further research to show whether neuroplastin also plays a role in other forms of learning.”