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bioRxiv · 10.1101/193508

Layer-Specific Molecular Dynamics of PKMζ in Sensorimotor Cortex During Acquisition and Storage of Procedural Memory

Gao, P. P.·Goodman, J. H.·Sacktor, T. C.·Francis, J. T.
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Abstract

Procedural memories, such as for riding a bicycle, can be maintained without practice for long periods of time and are thought to be supported by the persistent reorganization of sensorimotor cortices (S1/M1). Whereas enhanced synaptic strength and structural changes accompany the learning of motor tasks, the persistent molecular modifications that store long-term procedural memories within specific layers of sensorimotor cortex have not been identified. The persistent increase in the autonomously active, atypical PKC isoform, PKM{zeta}, is a putative molecular mechanism for maintaining enhanced synaptic strength during long-term potentiation (LTP) and several forms of long-term memory. Here we examine whether persistent increases in PKM{zeta} store long-term memory for a reaching task in rat sensorimotor cortex that could reveal the sites of procedural memory storage. Perturbing PKM{zeta} synthesis with PKM{zeta} -antisense oligodeoxynucleotides or blocking atypical PKC activity with zeta inhibitory peptide (ZIP) in S1/M1 disrupts and erases the maintenance of long-term motor memories. Only memories that are maintained without daily reinforcement are affected, indicating atypical PKCs (via ZIP) and PKM{zeta} specifically (via antisense) stores consolidated long-term procedural memories. Analysis of changes in the amount of PKM{zeta} in S1/M1 reveals PKM{zeta} increases in layers II/III and V of both S1 and M1 cortices as performance improves to an asymptote during training. After storage for 1 month without reinforcement, the increase in M1 layer V but not other layers persists without decrement. Thus, the sustained increases in PKM{zeta} reveal that the persistent molecular changes storing long-term procedural memory are localized to the descending output layer of primary motor cortex.

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Gao, P. P., Goodman, J. H., Sacktor, T. C., Francis, J. T.. 2017-09-25. Layer-Specific Molecular Dynamics of PKMζ in Sensorimotor Cortex During Acquisition and Storage of Procedural Memory. https://doi.org/10.1101/193508

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