Inhibition of acetylcholine-induced activation of extracellular regulated protein kinase prevents the encoding of an inhibitory avoidance response in the rat

• Published in: Neuroscience Vol. 136; no. 1; pp. 15 - 32
• Main Authors: Giovannini, M.G., Pazzagli, M., Malmberg-Aiello, P., Della Corte, L., Rakovska, A.D., Cerbai, F., Casamenti, F., Pepeu, G.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2005; Elsevier
• Subjects: Acetylcholine - metabolism; acetylcholine release; Animals; Avoidance Learning - drug effects; Avoidance Learning - physiology; Behavioral psychophysiology; Biological and medical sciences; Enzyme Activation - physiology; Enzyme Inhibitors - pharmacology; Extracellular Signal-Regulated MAP Kinases - metabolism; Fundamental and applied biological sciences. Psychology; glutamate; Glutamic Acid - metabolism; Hippocampus - metabolism; Male; MAPK; medial prefrontal cortex; Mental Recall - physiology; Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors; Muscarinic Antagonists - pharmacology; Neurotransmission and behavior; Prefrontal Cortex - metabolism; Prosencephalon - metabolism; Prosencephalon - physiology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; Rats, Wistar; Scopolamine Hydrobromide - pharmacology; short term memory; ventral hippocampus; Vertebrates: nervous system and sense organs; BB; OPA; ACd; medial prefrontal cortex; DG; DMSO; ACh; acetylcholine release; PBS-TX-NGS; AUC; CA1; FITC; CA3; ANOVA; short term memory; PD98059; glutamate; HPLC; U0126; PBS; IL; ventral hippocampus; DAB; PrL; MAPK; EDTA; PBS-T; S.E.M; EGTA; MEK; mPFC; VH; NeuN; BLA; aCSF; PBS-TX; ERK; Short term; Extracellular signal-regulated protein kinase; Rat; Memory; Central nervous system; Encephalon; Release; Enzyme; Rodentia; Mitogen-activated protein kinase; Prefrontal cortex; Glutamate; Vertebrata; Mammalia; Animal; Excitatory aminoacid; Neurotransmitter; Acetylcholine; Avoidance; Hippocampus
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2005.07.046

It has been demonstrated that the forebrain cholinergic system and the extracellular regulated kinase signal transduction pathway are involved in the mechanisms of learning, encoding, and storage of information. We investigated the involvement of the cholinergic and glutamatergic systems projecting to the medial prefrontal cortex and ventral hippocampus and of the extracellular regulated kinase signal transduction pathway in the acquisition and recall of the step-down inhibitory avoidance response in the rat, a relatively simple behavioral test acquired in a one-trial session. To this aim we studied by microdialysis the release of acetylcholine and glutamate, and by immunohistochemistry the activation of extracellular regulated kinase during acquisition, encoding and recall of the behavior. Cholinergic, but not glutamatergic, neurons projecting to the medial prefrontal cortex and ventral hippocampus were activated during acquisition of the task, as shown by increase in cortical and hippocampal acetylcholine release. Released acetylcholine in turn activated extracellular regulated kinase in neurons located in the target structures, since the muscarinic receptor antagonist scopolamine blocked extracellular regulated kinase activation. Both increased acetylcholine release and extracellular regulated kinase activation were necessary for memory formation, as administration of scopolamine and of extracellular regulated kinase inhibitors was followed by blockade of extracellular regulated kinase activation and amnesia. Our data indicate that a critical function of the learning-associated increase in acetylcholine release is to promote the activation of the extracellular regulated kinase signal transduction pathway and help understanding the role of these systems in the encoding of an inhibitory avoidance memory.