Lesions of the basal forebrain impair reversal learning but not shifting of attentional set in rats

doi:10.1016/j.bbr.2007.08.035

Behavioural Brain Research

Volume 187, Issue 1, 11 February 2008, Pages 100-108

https://doi.org/10.1016/j.bbr.2007.08.035 Get rights and content

Abstract

The cholinergic neurons of the basal forebrain, which project to cortex, the thalamic reticular nucleus and the amygdala, are implicated in many aspects of attentional function, while the intrinsic neurons of the basal forebrain are implicated in learning and memory. This study compared the effects of lesions of the basal forebrain made with either the immunotoxin 192-IgG-saporin (which selectively destroys cholinergic neurons), or the non-selective excitotoxin, ibotenic acid (which destroys both cholinergic and non-cholinergic neurons) on a task which measure the acquisition and shifting of attentional set as well as the ability to learn reversals of specific stimulus-reward pairings. Rats learned to obtain food reward by digging in small bowls containing distinctive digging media that were differentially scented with distinct odours. They performed a series of two-choice discriminations, with the bait associated with either the odour or the digging medium. Rats with 192-IgG-saporin lesions of the basal forebrain were not impaired relative to control rats at any stage of the task. Rats with ibotenic acid lesions of the basal forebrain were impaired the first time stimulus-reward contingencies were reversed. They were not impaired in acquisition of new discriminations, even when an attentional-shift was required. These data are consistent with data from marmosets and so highlight the functional similarity of monkey and rodent basal forebrain. They also confirm the likely involvement of non-cholinergic neurons of the basal forebrain in reversal learning.

Introduction

There is a substantial body of evidence to suggest the basal forebrain, and specifically the cholinergic projection from the basal forebrain, is involved in attention in a variety of contexts [12], [23], [28]. However, not all aspects of attention are impaired following basal forebrain lesions. For example, marmosets with N-methyl-d-aspartate lesions of the basal forebrain were able to attend selectively to relevant dimensions of complex, multi-dimensional stimuli associated with reward and to switch their attention when a different aspect of the stimulus became associated with reward. The lesion did, however, result in a deficit in reversal learning [27].

The contribution of the basal forebrain cholinergic and non-cholinergic neurons in attention and in learning and memory was examined by Page et al. [24] who compared directly lesions of the basal forebrain made with different excitotoxins resulting in different degrees of cholinergic depletions. The authors concluded that impairments in learning and memory were not due to loss of the cortical cholinergic projections from the basal forebrain, but rather due to damage within the basal forebrain itself. By contrast, attentional deficits were due to the compromised cholinergic projections.

The role of the basal forebrain cholinergic system in reversal learning and attentional set-shifting is still debatable, however. Cabrera et al. [5] have recently shown that 192-IgG-saporin lesions of basal forebrain impaired reversal learning in rats. However, in marmosets, selective lesions of the cholinergic basal forebrain with ME20.4 IgG-saporin did not impair reversal learning except when lesioned animals were further challenged with the muscarinic antagonist, scopolamine [13]. Although scopolamine-induced deficits in both reversal learning and attentional set-shifting have been reported in rats [7], the authors suggest the locus of this effect may be outside the prefrontal cortex. It is possible to dissociate the behavioural consequences of basal forebrain cholinergic versus non-cholinergic damage by comparing lesions made with 192-IgG-saporin with ibotenic acid-induced lesions (non-selective, but results in less cholinergic damage than other excitotoxins [11]). When directly compared, the performance deficits of 192-IgG-saporin lesioned rats were interpreted as impaired vigilance, whereas ibotenic acid lesions impaired switching between response patterns [4].

The task used to test the formation and shifting of attentional set in monkeys has been adapted for rats [2], [21]. In this study, therefore, we compared the effects of selective cholinergic (192-IgG-saporin) lesions and non-selective excitotoxic (ibotenic acid) lesions of the basal forebrain on the ability to form and shift attentional set and the ability to acquire and reverse stimulus-response associations in rats.

Section snippets

Material and methods

Forty-nine male Lister hooded rats (half from Charles River, UK and half from Harlan Olac, UK), naïve to behavioural testing, were used. The rats were pair-housed until surgery and maintained in a colony on a 12 h light/dark schedule (lights on at 7 am), with a diet of 15–20 g of standard laboratory chow each day with water freely available in the home cage. The weight range at the time of surgery was 330–470 g. At sacrifice, the weight range was 350–520 g. All procedures were carried out in

Histology

Rats administered 192-IgG-saporin was found to have a loss of VAChT-positive (i.e., cholinergic) neurons of the nucleus basalis magnocellularis/substantia innominata (mean 77 ± 2%; range 60–83% (n = 12)) compared to controls (Fig. 1, Fig. 2). In some subjects, this neuronal loss extended into the horizontal limb of the diagonal band of Broca and the magnocellular preoptic nucleus, most clearly seen closest to the site of infusion (stereotaxic co-ordinates, AP −0.6 through to −2.1 where the

Discussion

Ibotenic acid lesions of the basal forebrain, which resulted in a non-selective loss of basal forebrain neurons (including a 47% decrease in cholinergic neurons of the nucleus basalis magnocellularis) impaired discrimination reversal learning and interfered with the formation of an attentional set. However, selective lesions of the basal forebrain cholinergic neurons with 192-IgG-saporin, did not result in impairments of discrimination learning, reversal learning or the formation or shifting of

Acknowledgements

We gratefully acknowledge Dr. J. McGaughy for advice and assistance performing the 192-IgG-saporin lesions. We also acknowledge Mrs. M. Latimer for histological support.

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Research reportLesions of the basal forebrain impair reversal learning but not shifting of attentional set in rats

Abstract

Introduction

Section snippets

Material and methods

Histology

Discussion

Acknowledgements

Neuropsychologia

Neuroscience

Neuroscience

Brain Res

Brain Cogn

Neuroscience

Behav Brain Res

Neuroscience

Neuroscience

Neurobiol Learn Mem

Behav Brain Res

Int J Dev Neurosci

Neuroscience

Medial frontal cortex mediates perceptual attentional set shifting in the rat

J Neurosci

192 IgG-saporin: I. Specific lethality for cholinergic neurons in the basal forebrain of the rat

J Neuropathol Exp Neurol

Research report
Lesions of the basal forebrain impair reversal learning but not shifting of attentional set in rats