Drebrin depletion alters neurotransmitter receptor levels in protein complexes,dendritic spine morphogenesis and memory‐related synaptic plasticity in the mouse hippocampus
1. Department of Pediatrics, Medical University of Vienna, Vienna, Austria;2. Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria;3. Core Facility Imaging, Medical University of Vienna, Vienna, Austria;4. Core Unit of Biomedical Research, Division of Laboratory Animal Science and Genetics, Medical University of Vienna, Himberg, Austria;5. Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Vienna, Austria
Abstract:
Drebrin an actin‐bundling key regulator of dendritic spine genesis and morphology, has been recently proposed as a regulator of hippocampal glutamatergic activity which is critical for memory formation and maintenance. Here, we examined the effects of genetic deletion of drebrin on dendritic spine and on the level of complexes containing major brain receptors. To this end, homozygous and heterozygous drebrin knockout mice generated in our laboratory and related wild‐type control animals were studied. Level of protein complexes containing dopamine receptor D1/dopamine receptor D2, 5‐hydroxytryptamine receptor 1A (5‐HT1AR), and 5‐hydroxytryptamine receptor 7 (5‐HT7R) were significantly reduced in hippocampus of drebrin knockout mice whereas no significant changes were detected for GluR1, 2, and 3 and NR1 as examined by native gel‐based immunoblotting. Drebrin depletion also altered dendritic spine formation, morphology, and reduced levels of dopamine receptor D1 in dendritic spines as evaluated using immunohistochemistry/confocal microscopy. Electrophysiological studies further showed significant reduction in memory‐related hippocampal synaptic plasticity upon drebrin depletion. These findings provide unprecedented experimental support for a role of drebrin in the regulation of memory‐related synaptic plasticity and neurotransmitter receptor signaling, offer relevant information regarding the interpretation of previous studies and help in the design of future studies on dendritic spines.
