Recalling remote associative memories: Neuroplastin gene inactivation in GABAergic interneurons reveals endogenous mechanisms underlying selective retrograde amnesia.

• Applicant: Privatdozent Dr. Dirk Montag
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Experimental Models for the Understanding of Nervous System Diseases ; Experimental and Theoretical Network Neuroscience ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 526008379

During recent years, we have established a mouse model to induce retrograde amnesia of associative memories by neuroplastin (Nptn) gene ablation in all CNS neurons. This unique model allows the study of molecular and physiological process underlying retrograde amnesia. Furthermore, the learning and acquisition phases can be separated from memory recall, allowing to train mice under wild-type conditions and testing memory after Nptn ablation. In this proposal, we want to investigate the decisive neuron subtypes requiring neuroplastin using newly established mutants with inducible Nptn ablation specifically in gabaergic interneurons or in glutamatergic neurons. After behavioral characterization of associative learning and memory, we want to study whether electrophysiological properties of these neurons are altered and whether reduced extrusion of Ca2+ by neuroplastin-associated plasma membrane Calcium ATPases (PMCAs) confers retrograde amnesia. The electrophysiological studies will exploit a novel multi-electrode designed and patented in Magdeburg. In addition, we want to map brain activity patterns during memory recall using single-photon emission computed tomography (SPECT) imaging in awake mice. Our studies will not only increase the fundamental knowledge on memory recall and retrograde amnesia, but also will indicate points of intervention for the treatment of memory loss and post-traumatic stress disorder (PTSD).

• DFG Programme: Research Grants
• International Connection: Chile
• Cooperation Partner: Dr. Rodrigo Herrera-Molina, Ph.D.