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Hippocampal long term memory: effect of the cholinergic system on local protein synthesis.
Neurobiol Learn Mem. 2013 Nov; 106:246-57.NL

Abstract

The present study was aimed at establishing a link between the cholinergic system and the pathway of mTOR and its downstream effector p70S6K, likely actors in long term memory encoding. We performed in vivo behavioral experiments using the step down inhibitory avoidance test (IA) in adult Wistar rats to evaluate memory formation under different conditions, and immunohistochemistry on hippocampal slices to evaluate the level and the time-course of mTOR and p70S6K activation. We also examined the effect of RAPA, inhibitor of mTORC1 formation, and of the acetylcholine (ACh) muscarinic receptor antagonist scopolamine (SCOP) or ACh nicotinic receptor antagonist mecamylamine (MECA) on short and long term memory formation and on the functionality of the mTOR pathway. Acquisition test was performed 30 min after i.c.v. injection of RAPA, a time sufficient for the drug to diffuse to CA1 pyramidal neurons, as demonstrated by MALDI-TOF-TOF imaging. Recall test was performed 1 h, 4 h or 24 h after acquisition. To confirm our results we performed in vitro experiments on live hippocampal slices: we evaluated whether stimulation of the cholinergic system with the cholinergic receptor agonist carbachol (CCh) activated the mTOR pathway and whether the administration of the above-mentioned antagonists together with CCh could revert this activation. We found that (1) mTOR and p70S6K activation in the hippocampus were involved in long term memory formation; (2) RAPA administration caused inhibition of mTOR activation at 1 h and 4 h and of p70S6K activation at 4 h, and long term memory impairment at 24 h after acquisition; (3) scopolamine treatment caused short but not long term memory impairment with an early increase of mTOR/p70S6K activation at 1 h followed by stabilization at longer times; (4) mecamylamine plus scopolamine treatment caused short term memory impairment at 1 h and 4 h and reduced the scopolamine-induced increase of mTOR/p70S6K activation at 1 h and 4 h; (5) mecamylamine plus scopolamine treatment did not impair long term memory formation; (6) in vitro treatment with carbachol activated mTOR and p70S6K and this effect was blocked by scopolamine and mecamylamine. Taken together our data reinforce the idea that distinct molecular mechanisms are at the basis of the two different forms of memory and are in accordance with data presented by other groups that there exist molecular mechanisms that underlie short term memory, others that underlie long term memories, but some mechanisms are involved in both.

Authors+Show Affiliations

Department of Health Sciences, Section of Pharmacology and Clinical Oncology, University of Florence, Viale Pieraccini 6, 50139 Firenze, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24076274

Citation

Lana, Daniele, et al. "Hippocampal Long Term Memory: Effect of the Cholinergic System On Local Protein Synthesis." Neurobiology of Learning and Memory, vol. 106, 2013, pp. 246-57.
Lana D, Cerbai F, Di Russo J, et al. Hippocampal long term memory: effect of the cholinergic system on local protein synthesis. Neurobiol Learn Mem. 2013;106:246-57.
Lana, D., Cerbai, F., Di Russo, J., Boscaro, F., Giannetti, A., Petkova-Kirova, P., Pugliese, A. M., & Giovannini, M. G. (2013). Hippocampal long term memory: effect of the cholinergic system on local protein synthesis. Neurobiology of Learning and Memory, 106, 246-57. https://doi.org/10.1016/j.nlm.2013.09.013
Lana D, et al. Hippocampal Long Term Memory: Effect of the Cholinergic System On Local Protein Synthesis. Neurobiol Learn Mem. 2013;106:246-57. PubMed PMID: 24076274.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hippocampal long term memory: effect of the cholinergic system on local protein synthesis. AU - Lana,Daniele, AU - Cerbai,Francesca, AU - Di Russo,Jacopo, AU - Boscaro,Francesca, AU - Giannetti,Ambra, AU - Petkova-Kirova,Polina, AU - Pugliese,Anna Maria, AU - Giovannini,Maria Grazia, Y1 - 2013/09/27/ PY - 2013/06/11/received PY - 2013/09/17/revised PY - 2013/09/19/accepted PY - 2013/10/1/entrez PY - 2013/10/1/pubmed PY - 2014/8/12/medline KW - ACQ KW - ACh KW - Acetylcholine KW - CCh KW - IA KW - Inhibitory avoidance KW - Long term memory KW - M KW - MALDI-TOF-TOF KW - MECA KW - Mecamylamine KW - RAPA KW - REC KW - Rapamycin KW - SCOP KW - SEM KW - Scopolamine KW - aCSF KW - acetylcholine KW - acquisition KW - artificial cerebrospinal fluid KW - carbachol KW - mAChR KW - mTOR KW - mTORC1 KW - mammalian target of rapamycin KW - mammalian target of rapamycin complex 1 KW - matrix assited laser desorption ionization-time of flight-time of flight KW - mean KW - mecamylamine KW - muscarinic acetylcholine receptors KW - nAChR KW - nicotinic acetylcholine receptors KW - p70S6K KW - p70S6Kinase KW - rapamycin KW - recall KW - scopolamine KW - standard error of the mean KW - step-down inhibitory avoidance SP - 246 EP - 57 JF - Neurobiology of learning and memory JO - Neurobiol Learn Mem VL - 106 N2 - The present study was aimed at establishing a link between the cholinergic system and the pathway of mTOR and its downstream effector p70S6K, likely actors in long term memory encoding. We performed in vivo behavioral experiments using the step down inhibitory avoidance test (IA) in adult Wistar rats to evaluate memory formation under different conditions, and immunohistochemistry on hippocampal slices to evaluate the level and the time-course of mTOR and p70S6K activation. We also examined the effect of RAPA, inhibitor of mTORC1 formation, and of the acetylcholine (ACh) muscarinic receptor antagonist scopolamine (SCOP) or ACh nicotinic receptor antagonist mecamylamine (MECA) on short and long term memory formation and on the functionality of the mTOR pathway. Acquisition test was performed 30 min after i.c.v. injection of RAPA, a time sufficient for the drug to diffuse to CA1 pyramidal neurons, as demonstrated by MALDI-TOF-TOF imaging. Recall test was performed 1 h, 4 h or 24 h after acquisition. To confirm our results we performed in vitro experiments on live hippocampal slices: we evaluated whether stimulation of the cholinergic system with the cholinergic receptor agonist carbachol (CCh) activated the mTOR pathway and whether the administration of the above-mentioned antagonists together with CCh could revert this activation. We found that (1) mTOR and p70S6K activation in the hippocampus were involved in long term memory formation; (2) RAPA administration caused inhibition of mTOR activation at 1 h and 4 h and of p70S6K activation at 4 h, and long term memory impairment at 24 h after acquisition; (3) scopolamine treatment caused short but not long term memory impairment with an early increase of mTOR/p70S6K activation at 1 h followed by stabilization at longer times; (4) mecamylamine plus scopolamine treatment caused short term memory impairment at 1 h and 4 h and reduced the scopolamine-induced increase of mTOR/p70S6K activation at 1 h and 4 h; (5) mecamylamine plus scopolamine treatment did not impair long term memory formation; (6) in vitro treatment with carbachol activated mTOR and p70S6K and this effect was blocked by scopolamine and mecamylamine. Taken together our data reinforce the idea that distinct molecular mechanisms are at the basis of the two different forms of memory and are in accordance with data presented by other groups that there exist molecular mechanisms that underlie short term memory, others that underlie long term memories, but some mechanisms are involved in both. SN - 1095-9564 UR - https://www.unboundmedicine.com/medline/citation/24076274/Hippocampal_long_term_memory:_effect_of_the_cholinergic_system_on_local_protein_synthesis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1074-7427(13)00190-1 DB - PRIME DP - Unbound Medicine ER -