title: Damage of GABAergic neurons in the medial septum impairs spatial working memory and extinction of active avoidance: effects on proactive interference.
abstract: The medial septum and diagonal band (MSDB) are important in spatial learning and memory. On the basis of the excitotoxic damage of GABAergic MSDB neurons, we have recently suggested a role for these neurons in controlling proactive interference. Our study sought to test this hypothesis in different behavioral procedures using a new GABAergic immunotoxin. GABA-transporter-saporin (GAT1-SAP) was administered into the MSDB of male Sprague-Dawley rats. Following surgery, rats were trained in a reference memory water maze procedure for 5 days, followed by a working memory (delayed match to position) water maze procedure. Other rats were trained in a lever-press avoidance procedure after intraseptal GAT1-SAP or sham surgery. Intraseptal GAT1-SAP extensively damaged GABAergic neurons while sparing most cholinergic MSDB neurons. Rats treated with GAT1-SAP were not impaired in acquiring a spatial reference memory, learning the location of the escape platform as rapidly as sham rats. In contrast, GAT1-SAP rats were slower than sham rats to learn the platform location in a delayed match to position procedure, in which the platform location was changed every day. Moreover, GAT1-SAP rats returned to previous platform locations more often than sham rats. In the active avoidance procedure, intraseptal GAT1-SAP impaired extinction but not acquisition of the avoidance response. Using a different neurotoxin and behavioral procedures than previous studies, the results of this study paint a similar picture that GABAergic MSDB neurons are important for controlling proactive interference.
authors.affiliation: NeuroBehavioral Laboratory, Department of Veterans Affairs, New Jersey Health Care System, East Orange, New Jersey 07018, USA. kevin.pang@va.gov
authors.forename: Kevin C H
authors.initials: KC
authors.lastname: Pang
authors.forename: Xilu
authors.initials: X
authors.lastname: Jiao
authors.forename: Swamini
authors.initials: S
authors.lastname: Sinha
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Beck
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Servatius
mesh_terms: D000818:Animals; D002795:Choline O-Acetyltransferase / Q000276:immunology; D020667:Diagonal Band of Broca / Q000166:cytology / Q000502:physiology*; D004195:Disease Models, Animal; D050485:GABA Plasma Membrane Transport Proteins / Q000008:administration & dosage; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D000922:Immunotoxins / Q000008:administration & dosage; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D011334:Proactive Inhibition; D051381:Rats; D017207:Rats, Sprague-Dawley; D054789:Ribosome Inactivating Proteins, Type 1 / Q000008:administration & dosage; D000076985:Saporins; D020665:Septum of Brain / Q000166:cytology / Q000502:physiology*; D013028:Space Perception / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D050485:GABA Plasma Membrane Transport Proteins; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; C493415:Slc6a1 protein, rat; D005680:gamma-Aminobutyric Acid; D002795:Choline O-Acetyltransferase; D000076985:Saporins