Damage of GABAergic neurons in the medial septum impairs spatial working memory and extinction of active avoidance: Effects on proactive interference

摘要

The medial septum and diagonal band (MSDB) are important in spatial learning and memory. Based on excitotoxic damage of GABAergic MSDB neurons, we have recently suggested a role for these neurons in controlling proactive interference. The present study sought to test this hypothesis in different behavioral procedures using a new GABAergic immunotoxin. GAT1-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 produced extensive damage of GABAergic 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 the present study paint a similar picture that GABAergic MSDB neurons are important for controlling proactive interference.