Microtubules to form memory.
ABSTRACT Microtunbule-depolymerizing agents cause amnesia. Some signal translocations to the stimulated postsynaptic membrane are essential for inducing LTP in CA1 neurons like AMPA receptors, CaMKII and mRNA. On the other hand, LTP requires protein synthesis and gene expression. This indicates that signals generated at the synapse might be transmitted to the nucleus. Recently, we have reported that LTP-producing stimulation makes new microtubule track between cell body and the stimulated postsynaptic membrane in CA1 neurons. This newly produced microtubule track only to the stimulated postsynaptic membrane might be the route of these bi-directional transportation of signals during LTP formation. This lead us the hypothesis of the "endless memory amplifying circuit" that means gene expression-promoting molecules are translocated from postsynaptic membrane to the cell body and enter into nucleus and activate transcription factors, and gene products, which will probably promote plasticity, may be re-translocated only to the stimulated postsynaptic membrane along microtubules.
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ABSTRACT: Morphine's effects on learning and memory processes are well known to depend on synaptic plasticity in the hippocampus. Whereas the role of the hippocampus in morphine-induced amnesia and state-dependent learning is established, the biochemical and molecular mechanisms underlying these processes are poorly understood. The present study intended to investigate whether administration of morphine can change the expression level of rat hippocampal proteins during learning of a passive avoidance task. A step-through type passive avoidance task was used for the assessment of memory retention. To identify the complex pattern of protein expression induced by morphine, we compared rat hippocampal proteome either in morphine-induced amnesia or in state-dependent learning by two-dimensional gel electerophoresis and combined mass spectrometry (MS and MS/MS). Post-training administration of morphine decreased step-through latency. Pre-test administration of morphine induced state-dependent retrieval of the memory acquired under post-training morphine influence. In the hippocampus, a total of 18 proteins were identified whose MASCOT (Modular Approach to Software Construction Operation and Test) scores were inside 95% confidence level. Of these, five hippocampal proteins altered in morphine-induced amnesia and ten proteins were found to change in the hippocampus of animals that had received post-training and pre-test morphine. These proteins show known functions in cytoskeletal architecture, cell metabolism, neurotransmitter secretion and neuroprotection. The findings indicate that the effect of morphine on memory formation in passive avoidance learning has a morphological correlate on the hippocampal proteome level. In addition, our proteomicscreensuggests that morphine induces memory impairment and state-dependent learning through modulating neuronal plasticity.Iranian journal of pharmaceutical research (IJPR) 01/2015; 14(2):591-602. · 0.51 Impact Factor
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ABSTRACT: There are many microtubules in axons and dendritic shafts, but it has been thought that there were fewer microtubules in spines. Recently, there have been four reports that observed the intraspinal microtubules. Because microtubules originate from the centrosome, these four reports strongly suggest a stimulation-dependent connection between the nucleus and the stimulated postsynaptic membrane by microtubules. In contrast, several pieces of evidence suggest that spine elongation may be caused by the polymerization of intraspinal microtubules. This structural mechanism for spine elongation suggests, conversely, that the synapse loss or spine loss observed in Alzheimer's disease may be caused by the depolymerization of intraspinal microtubules. Based on this evidence, it is suggested that the impairment of intraspinal microtubules may cause spinal structural change and block the translocation of plasticity-related molecules between the stimulated postsynaptic membranes and the nucleus, resulting in the cognitive deficits of Alzheimer's disease.03/2012; 2012:519682. DOI:10.1155/2012/519682