Abstract
We investigated the role of the septo-hippocampal cholinergic projection in anxiety, spatial novelty preference, and differential reward for low rates of responding (DRL) performance. Cholinergic neurons of the rat medial septum (MS) and the vertical limb of the diagonal band of Broca (VDB) were lesioned using the selective immunotoxin, 192 IgG-saporin. Rats were then tested on several behavioral tests previously shown to be sensitive to either (a) hippocampal lesions or (b) nonselective MS/VDB lesions which target both cholinergic and γ-aminobutyric acid (GABA)-ergic projections, or both. Saporin lesions substantially reduced hippocampal cholinergic innervation, resulting in an absence of acetyl cholinesterase staining and markedly reduced choline acetyltransferase activity (mean reduction: 80 ± 5%; range: 50–97%). However, the saporin-lesioned rats did not differ from control rats in any of the behavioral tests. Thus we found no evidence from these lesion studies that the septo-hippocampal cholinergic projection plays an essential role in anxiety, spatial novelty preference, or DRL.
Highlights
MethodsThis study used 36 naïve male Lister-Hooded rats (Harlan Olac, Bicester, U.K.), weighing between 310 and 385 g at the start of the experiment
We found no evidence for similar effects in the present study, either during the test of spontaneous locomotor activity which examined exploratory activity in a novel cage environment (Experiment 1), or during the spatial novelty preference test which provides a stimulus-specific assay of spatial short-term memory (STM) for recently experienced locations (Experiment 4)
In our pilot studies we found that injecting a 0.2 ug/l concentration of the toxin caused damage to cholinergic cells and to GABA-ergic cells in the MS/VDB
Summary
This study used 36 naïve male Lister-Hooded rats (Harlan Olac, Bicester, U.K.), weighing between 310 and 385 g at the start of the experiment. They were housed in a temperature- and humiditycontrolled room under a 12-hr light– dark cycle (lights on 0700 – 1900). Testing took place during the light cycle. Rats were housed three per cage with ad libitum food and water unless otherwise specified. The experiments were conducted in accordance with the United Kingdom Animals Scientific Procedures Act (1986) under project license PPL 30/1989.
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