title: Selective cholinergic depletion in medial septum leads to impaired long term potentiation and glutamatergic synaptic currents in the hippocampus.
abstract: Cholinergic depletion in the medial septum (MS) is associated with impaired hippocampal-dependent learning and memory. Here we investigated whether long term potentiation (LTP) and synaptic currents, mediated by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the CA1 hippocampal region, are affected following cholinergic lesions of the MS. Stereotaxic intra-medioseptal infusions of a selective immunotoxin, 192-saporin, against cholinergic neurons or sterile saline were made in adult rats. Four days after infusions, hippocampal slices were made and LTP, whole cell, and single channel (AMPA or NMDA receptor) currents were recorded. Results demonstrated impairment in the induction and expression of LTP in lesioned rats. Lesioned rats also showed decreases in synaptic currents from CA1 pyramidal cells and synaptosomal single channels of AMPA and NMDA receptors. Our results suggest that MS cholinergic afferents modulate LTP and glutamatergic currents in the CA1 region of the hippocampus, providing a potential synaptic mechanism for the learning and memory deficits observed in the rodent model of selective MS cholinergic lesioning.
authors.affiliation: Department of Pharmacal Sciences, Auburn University, Auburn, Alabama, United States of America.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kanju
authors.forename: Kodeeswaran
authors.initials: K
authors.lastname: Parameshwaran
authors.forename: Catrina
authors.initials: C
authors.lastname: Sims-Robinson
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Uthayathas
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Josephson
authors.forename: Nagalingam
authors.initials: N
authors.lastname: Rajakumar
authors.forename: Muralikrishnan
authors.initials: M
authors.lastname: Dhanasekaran
authors.forename: Vishnu
authors.initials: V
authors.lastname: Suppiramaniam
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D018678:Cholinergic Agents / Q000494:pharmacology; D059329:Cholinergic Neurons / Q000187:drug effects / Q000378:metabolism*; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D007124:Immunoenzyme Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D054789:Ribosome Inactivating Proteins, Type 1 / Q000494:pharmacology*; D000076985:Saporins; D020665:Septum of Brain / Q000187:drug effects / Q000293:injuries / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism*
chemical_list: C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D016194:Receptors, N-Methyl-D-Aspartate; D054789:Ribosome Inactivating Proteins, Type 1; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000076985:Saporins