Basolateral amygdala lesions disrupt latent inhibitionin rats
Introduction
Latent inhibition (LI) refers to the slowed acquisition of conditioned responding produced by repeated non-reinforced preexposure of a conditioned stimulus (CS) prior to conditioning [25]. It has been hypothesised that this LI effect represents a deficit in the acquisition of CS-unconditioned stimulus (US) associations, variously attributed to a decrease of associability of the CS [33], the conditioning of inattention [26], or reduced processing of the CS as a result of priming by the preexposure context [36]. It has also been proposed that LI may not result from impaired acquisition, but may instead be due to interference processes, such that competition from learning that occurred during preexposure prevents behavioural expression of learning derived from the conditioning stage of the experiment [9].
Irrespective of these different theoretical interpretations, it has been repeatedly suggested that LI may provide a useful animal model of cognitive impairments observed in acute schizophrenia. As a consequence, there has been a good deal of interest in the neural substrates of the LI effect [38], and it has been suggested that the neural circuitry of LI depends, at least in part, on the integrity of temporal lobe structures [10], and the interaction of these structures with subcortical regions such as the nucleus accumbens. Indeed, it has been convincingly demonstrated that, within the hippocampal formation, the entorhinal cortex plays a key role in the control of LI. Whereas selective lesions of the hippocampus or subiculum were without effect (3, 15 but see [11]), selective lesions of the entorhinal cortex disrupted LI 3, 4, 39, 40.
The role of another significant temporal lobe structure, the amygdala, has not been fully investigated. This structure is of particular interest because it has both direct and indirect projections to the nucleus accumbens and prefrontal cortex, regions strongly associated with neuropathological changes underlying schizophrenia. To date, submaximal electrolytic lesions of the basolateral nucleus of the amygdala (BLA) and excitotoxic lesions of the central nucleus have been shown to have no effect on LI in aversive and appetitive procedures respectively 13, 37.
However, there are reasons to examine more closely the results of the previous study investigating the role of the BLA in LI. First, there is abundant evidence that damage to the BLA can disrupt basic fear conditioning 5, 24, possibly compromising interpretation of effects on LI. Second, the submaximal nature of the lesions (lesion groups were separated on the basis of the restricted anterior vs. posterior level of damage to the BLA) leaves open the possibility that more complete lesions might influence the LI effect. For these reasons, we decided to examine further the possible role of the BLA in LI.
In contrast to aversive Pavlovian fear-conditioning procedures, there is good evidence that lesions of the BLA have no substantial effect on appetitive Pavlovian conditioning 2, 12. Hence, LI was assessed using an appetitive conditioning procedure involving the acquisition of magazine approach behaviour in response to an auditory CS paired with a food US. Preexposing the CS alone prior to the conditioning phase results in a reduced conditioned response, that is a LI effect. The level of preexposure was chosen to induce robust LI, as reported elsewhere previously 19, 20. We assessed the effects of quinolinic acid induced-lesion of the entire extent of the BLA in this preparation.
Section snippets
Subjects
Nineteen male, Lister-hooded rats (275–300 g) obtained from Charles River (UK) were used. Rats were accustomed to the laboratory vivarium for 1 week. They were housed two per cage and after recovery from surgery were maintained on a 22.5-h schedule of food deprivation. During deprivation, food was made available between 1630 and 1800 h daily. The vivarium in which the rats were housed was maintained at 21°C with the light on from 0800 to 2000 h. All experiments were carried out during the light
Histological verification
Figure 1 shows schematic representations of the smallest (black) and largest (grey) lesions of the BLA. In all lesioned rats, the lesion was found to be acceptable, and included the entire BLA. Typical lesions extended from −1.8 mm to −3.3 mm posterior to bregma. At the more rostral levels (from −2.8 to −3.3 mm posterior to bregma), the central nucleus, as well as some of the piriform cortex, was damaged unilaterally in 5 of 11 rats. No damage was observed in sham-operated rats.
Behavioural effects
One animal in
Discussion
The main result of the present study is that excitotoxic lesion of the BLA produced a significant disruption of the LI effect in a within-subjects appetitive Pavlovian conditioning procedure.
The data from the SHAM group indicate that our preexposure conditions induced robust LI, confirming previous results from our lab 19, 20. In BLA-lesioned animals, the acquisition of conditioned responding to the non-preexposed stimulus was similar to that obtained in the SHAM group, suggesting that BLA
Acknowledgements
This study was supported by a project grant from the Wellcome trust to S.K., and a UK MRC research studentship to P.J.B.
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