Sinha SP, Roland JJ, Servatius RJ, Pang KCH (2011) The role of medial septal/diagonal band GABAergic neurons in proactive interference: Effects of selective immunotoxic lesions in latent inhibition. Neuroscience 2011 Abstracts 199.22. Society for Neuroscience, Washington, DC.
Summary: The medial septum/diagonal band (MSDB) is a critical structure for learning and memory, yet the functional contributions of its individual neuronal populations (including cholinergic, GABAergic, glutamatergic and peptidergic cells) are still being characterized. Recent studies have implicated a contributing role for the GABAergic MSDB neuronal population, as selective immunotoxic GABAergic lesions of the MSDB (with GAT1-saporin) produce behavioral impairments in spatial and instrumental tasks. Compared to intact controls, rats with GABAergic MSDB lesions are impaired in learning new spatial locations in a delayed match to position procedure and also exhibit a slower rate of extinguishing a previously acquired avoidance response – behaviors that are consistent with an exacerbation of proactive interference. To further establish the role of these neurons in proactive interference, this study examined the effects of selective GABAergic MSDB lesions in latent inhibition (LI) of the classically conditioned eyeblink response. LI in delay eyeblink conditioning is a phenomenon in which pre-exposure to the conditioned stimulus (CS) interferes with the subjects’ ability to subsequently associate the CS with an unconditioned stimulus (US), resulting in slower acquisition of the conditioned response (CR). We hypothesized that if damage of GABAergic MSDB neurons increases proactive interference, then rats with selective lesions of these neurons would show facilitated LI. Male Sprague-Dawley rats (n=18) were administered either phosphate-buffered saline or GAT1-saporin via intracranial injection into the MSDB. After 7-10 days of recovery, electrodes were implanted into the upper eyelids of the rats for delivery of US and EMG recording. Conditioning began after another 5-7 days of recovery, with Day 1 consisting of 30 minutes of acclimation to the conditioning context. Day 2 began with either 30 presentations of the CS (82dB, 500ms white noise, 25 – 35s ITI) or context pre-exposure of equal duration, followed immediately by 100 paired CS-US trials (82 dB, 500ms white noise co-terminating with a 10V, 10ms square-wave stimulus). In preliminary results, intraseptal GAT1-saporin did not alter CR acquisition in context pre-exposed rats. Rats with GABAergic MSDB lesions continued to exhibit latent inhibition. These preliminary results do not support the idea that damage of GABAergic MSDB neurons increase proactive interference of the classically conditioned eyeblink response. Future studies will examine whether manipulations of the number of CS pre-exposures would facilitate LI in rats with GABAergic MSDB lesions.
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