scholarly journals Persistent increases of PKMζ in sensorimotor cortex maintain procedural long-term memory storage

2017 ◽  
Author(s):  
Peng P. Gao ◽  
Jeffrey H. Goodman ◽  
Todd C. Sacktor ◽  
Joseph T. Francis

SummaryProcedural 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, PKMζ, 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 PKMζ store long-term memory for a reaching task in rat sensorimotor cortex that could reveal the sites of procedural memory storage. Perturbing PKMζ synthesis with PKMζ -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 PKMζ specifically (via antisense) stores consolidated long-term procedural memories. Analysis of changes in the amount of PKMζ in S1/M1 reveals PKMζ 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 PKMζ reveal that the persistent molecular changes storing long-term procedural memory are localized to the descending output layer of primary motor cortex.

iScience ◽  
2018 ◽  
Vol 5 ◽  
pp. 90-98 ◽  
Author(s):  
Peng Penny Gao ◽  
Jeffrey H. Goodman ◽  
Todd Charlton Sacktor ◽  
Joseph Thachil Francis

Author(s):  
Ishanee Das Sharma

This review aims to clarify and classify memory from psychological and neuroscientific point of view, delving into the molecular mechanisms taking place as well. The main forms of memory are sensory memory, short term memory and long-term memory. We also try to specify the flow of information through various memory models. The concept of synaptic plasticity and long-term potentiation is highlighted, with special focus on the physiological parts of the brain that are involved in memory storage. Overall, this study will help expand our knowledge on the intrinsic details of memory storage and the functioning of our brain.


2020 ◽  
Author(s):  
Changchi Hsieh ◽  
Panayiotis Tsokas ◽  
Ain Chung ◽  
Claudia Garcia-Jou ◽  
Edith Lesburguères ◽  
...  

PKMζ is an autonomously active, atypical PKC isoform crucial for maintaining synaptic long-term potentiation (LTP) and long-term memory. Unlike other PKCs that are transiently activated by short-lived second messengers, PKMζ is persistently activated by long-lasting increases in the amount of the autonomously active kinase during LTP and long-term memory maintenance. Thus, localizing persistent increases in PKMζ might reveal traces of physiological LTP maintenance in the circuitry of the brain during long-term memory storage. Using quantitative immunohistochemistry validated by the lack of staining in PKMζ-null mice, we visualized the amount and distribution of PKMζ during LTP maintenance and spatial long-term memory storage in the hippocampal formation of wild-type mice. Strong afferent stimulation of Schaffer collateral/commissural fibers inducing LTP maintenance increases PKMζ in CA1 pyramidal cells for 2 hours in hippocampal slices. Active place avoidance spatial conditioning increases PKMζ in CA1 pyramidal cells of the hippocampal formation from 1 day to at least 1 month. The increases in PKMζ coincide with the location of cells marked during long-term memory training by Arc promoter-mediated expression of a fluorescent protein, including at dendritic spines. We conclude that increased PKMζ forms persistent traces in CA1 pyramidal cells that are sites of molecular information storage during LTP maintenance and spatial long-term memory.Graphical AbstractPKMζ-immunohistochemistry reveals persistent increased PKMζ in the hippocampus during (A) LTP maintenance, and (B) spatial long-term memory storage.


2018 ◽  
Author(s):  
Peng P. Gao ◽  
Jeffrey H. Goodman ◽  
Todd C. Sacktor ◽  
Joseph T. Francis

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130140 ◽  
Author(s):  
A. Iván Hernández ◽  
William C. Oxberry ◽  
John F. Crary ◽  
Suzanne S. Mirra ◽  
Todd Charlton Sacktor

In contrast to protein kinases that participate in long-term potentiation (LTP) induction and memory consolidation, the autonomously active atypical protein kinase C isoform, protein kinase Mzeta (PKMζ), functions in the core molecular mechanism of LTP maintenance and long-term memory storage. Here, using multiple complementary techniques for light and electron microscopic immunolocalization, we present the first detailed characterization of the cellular and subcellular distribution of PKMζ in rat hippocampus and neocortex. We find that PKMζ is widely expressed in forebrain with prominent immunostaining in hippocampal and neocortical grey matter, and weak label in white matter. In hippocampal and cortical pyramidal cells, PKMζ expression is predominantly somatodendritic, and electron microscopy highlights the kinase at postsynaptic densities and in clusters within spines. In addition, nuclear label and striking punctate immunopositive structures in a paranuclear and dendritic distribution are seen by confocal microscopy, occasionally at dendritic bifurcations. PKMζ immunoreactive granules are observed by electron microscopy in cell bodies and dendrites, including endoplasmic reticulum. The widespread distribution of PKMζ in nuclei, nucleoli and endoplasmic reticulum suggests potential roles of this kinase in cell-wide mechanisms involving gene expression, biogenesis of ribosomes and new protein synthesis. The localization of PKMζ within postsynaptic densities and spines suggests sites where the kinase stores information during LTP maintenance and long-term memory.


Author(s):  
Mohammad B. Azzam ◽  
Ronald A. Easteal

AbstractClearly, memory and learning are essential to medical education. To make memory and learning more robust and long-term, educators should turn to the advances in neuroscience and cognitive science to direct their efforts. This paper describes the memory pathways and stages with emphasis leading to long-term memory storage. Particular stress is placed on this storage as a construct known as schema. Leading from this background, several pedagogical strategies are described: cognitive load, dual encoding, spiral syllabus, bridging and chunking, sleep consolidation, and retrieval practice.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Hamish Patel ◽  
Reza Zamani

Abstract Long-term memories are thought to be stored in neurones and synapses that undergo physical changes, such as long-term potentiation (LTP), and these changes can be maintained for long periods of time. A candidate enzyme for the maintenance of LTP is protein kinase M zeta (PKMζ), a constitutively active protein kinase C isoform that is elevated during LTP and long-term memory maintenance. This paper reviews the evidence and controversies surrounding the role of PKMζ in the maintenance of long-term memory. PKMζ maintains synaptic potentiation by preventing AMPA receptor endocytosis and promoting stabilisation of dendritic spine growth. Inhibition of PKMζ, with zeta-inhibitory peptide (ZIP), can reverse LTP and impair established long-term memories. However, a deficit of memory retrieval cannot be ruled out. Furthermore, ZIP, and in high enough doses the control peptide scrambled ZIP, was recently shown to be neurotoxic, which may explain some of the effects of ZIP on memory impairment. PKMζ knockout mice show normal learning and memory. However, this is likely due to compensation by protein-kinase C iota/lambda (PKCι/λ), which is normally responsible for induction of LTP. It is not clear how, or if, this compensatory mechanism is activated under normal conditions. Future research should utilise inducible PKMζ knockdown in adult rodents to investigate whether PKMζ maintains memory in specific parts of the brain, or if it represents a global memory maintenance molecule. These insights may inform future therapeutic targets for disorders of memory loss.


2013 ◽  
Vol 4 (1) ◽  
pp. 1-9
Author(s):  
Fitriati

Memory obviously plays an important role in knowledge retention. In particular, when learning mathematics students claim that much of what is taught in classrooms is soon forgotten and learning mathematics is difficult or not interesting. Neuroscience, through its study on long term memory, has tried to identify why these phenomena occur. Then some possible solutions are suggested. Understanding the processes of memory storage including acquisition, consolidation, recoding, storing and retrieval helps teachers to efficiently plan for effective learning activities. Therefore, this paper outlines the potential implication of long term memory to mathematics learning as well as suggests some learning strategies that might solve students‟ and teachers‟ problem in learning mathematics.


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