Persistent Increases of PKMζ in Sensorimotor Cortex Maintain Procedural Long-Term Memory Storage

• Published in: iScience Vol. 5; pp. 90 - 98
• Main Authors: Gao, Peng Penny, Goodman, Jeffrey H., Sacktor, Todd Charlton, Francis, Joseph Thachil
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.07.2018; Elsevier
• Subjects: Behavioral Neuroscience; Molecular Neuroscience; Neuroscience; Behavioral Neuroscience; Molecular Neuroscience; Neuroscience
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2018.07.002

Procedural motor learning and memory are accompanied by changes in synaptic plasticity, neural dynamics, and synaptogenesis. Missing is information on the spatiotemporal dynamics of the molecular machinery maintaining these changes. Here we examine whether persistent increases in PKMζ, an atypical protein kinase C (PKC) isoform, store long-term memory for a reaching task in rat sensorimotor cortex that could reveal the sites of procedural memory storage. Specifically, perturbing PKMζ synthesis (via antisense oligodeoxynucleotides) and blocking atypical PKC activity (via zeta inhibitory peptide [ZIP]) in S1/M1 disrupts and erases long-term motor memory maintenance, indicating atypical PKCs and specifically PKMζ store consolidated long-term procedural memories. Immunostaining reveals that PKMζ increases in S1/M1 layers II/III and V as performance improved to an asymptote. After storage for 1 month without reinforcement, the increase in M1 layer V persists without decrement. Thus, the persistent increases in PKMζ that store long-term procedural memory are localized to the descending output layer of the primary motor cortex. [Display omitted] •Perturbing PKMζ synthesis in S1/M1 slows the formation of skilled motor memory•Blocking PKMζ activity specifically erases memories maintained without reinforcement•Skilled motor learning induces the increase of PKMζ in S1/M1 layers II/III and V•PKMζ sustains the engram for procedural motor memory in M1 layer V Neuroscience; Behavioral Neuroscience; Molecular Neuroscience