title: Presynaptic muscarinic receptors reduce synaptic depression and facilitate its recovery at hippocampal GABAergic synapses.
abstract: Hippocampal gamma oscillation, involved in cognitive processes, can be induced by muscarinic acetylcholine receptors activation and depends in large part on the activation of γ-aminobutyric acidergic (GABAergic) interneurons. The precise role of the modulatory action of muscarinic receptors on GABAergic transmission still remains unclear due to the great heterogeneity of observed effects. We have examined the presynaptic and postsynaptic mechanisms involved. Methacholine induces a down-regulation of evoked inhibitory postsynaptic currents (eIPSCs) not associated with the change of postsynaptic receptors. The significant decrease in the paired-pulse depression strongly suggested a presynaptic mechanism of action. We have used cumulative amplitude profile analysis to show that the impairment of eIPSCs is not related to a decreased size of the readily releasable pool, but rather depends on the reduced release probability by a down-modulation of voltage-gated calcium channels. The decreased neurotransmitter release probability only partially accounts for the dramatic reduction in the rate of synaptic depression evoked by short- and long-lasting tetanic stimuli. This effect is accompanied by a significant enhancement in the rate of recovery from synaptic depression that demonstrates the reinforcement of the synaptic recycling processes. These results show that muscarinic modulation of hippocampal GABAergic synapses confers a greater resistance to sustain periods of intense synaptic activity in the gamma frequency range.
authors: Departament of Pharmacology and Therapeutics, Instituto Teófilo Hernando.
authors: J C
authors: JC
authors: González
authors: Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genova, Italy and Department of Experimental Medicine, University of Genova, 16100 Genova, Italy.
authors: G
authors: G
authors: Lignani
authors: Departament of Pharmacology and Therapeutics, Instituto Teófilo Hernando.
authors: M
authors: M
authors: Maroto
authors: Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genova, Italy and Department of Experimental Medicine, University of Genova, 16100 Genova, Italy.
authors: P
authors: P
authors: Baldelli
authors: Departament of Pharmacology and Therapeutics, Instituto Teófilo Hernando, Instituto de Investigación Sanitaria Hospital de la Princesa, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid 28029, Spain.
authors: J M
authors: JM
authors: Hernández-Guijo
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D059330:GABAergic Neurons / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D011247:Pregnancy; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013569:Synapses / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D026941:Sodium Channel Blockers; D016210:Methacholine Chloride; D013779:Tetrodotoxin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine
keywords: hippocampal neurons; methacholine; muscarinic receptors; γ-aminobutyric acidergic synapses