The switching model of latent inhibition: an update of neural substrates

doi:10.1016/S0166-4328(97)02314-0

Behavioural Brain Research

Volume 88, Issue 1, October 1997, Pages 11-25

https://doi.org/10.1016/S0166-4328(97)02314-0 Get rights and content

Abstract

Organisms exposed to a stimulus which has no significant consequences, show subsequently latent inhibition (LI), namely, retarded conditioning to this stimulus. LI is considered to index the capacity to ignore irrelevant stimuli and its disruption has recently received increasing interest as an animal model of cognitive deficits in schizophrenia. Initial studies indicated that LI is disrupted by systemic or intra-accumbens injections of amphetamine and hippocampal lesions, and potentiated by systemic administration of neuroleptics. On the basis of these findings, the switching model of LI proposed that LI depends on the subicular input to the nucleus accumbens (NAC). Subsequent studies supported and refined this proposition. Lesion studies show that LI is indeed disrupted by severing the subicular input to the NAC, and further implicate the entorhinal/ventral subicular portion of this pathway projecting to the shell subterritory of the NAC. There is a functional dissociation between the shell and core subterritories of the NAC, with lesions of the former but not of the latter disrupting LI. This suggests that the shell is necessary for the expression and the core for the disruption of LI. The involvement of the NAC has been also demonstrated by findings that LI is disrupted by intra-accumbens injection of amphetamine and potentiated by DA depletion or blockade in this structure. Disruption and potentiation of LI by systemic administration of amphetamine and neuroleptics, respectively, have been firmly established, and in addition, have been shown to be sensitive to parametric manipulations of the LI procedure. LI is unaffected by lesions and DA manipulations of medial prefrontal cortex and lesions of basolateral amygdala. The implications of these findings for LI as an animal model of schizophrenia are discussed.

Section snippets

Latent Inhibition (LI)

If a stimulus (e.g. tone or light) is repeatedly pre-exposed without consequences, it subsequently develops a weaker association with a reinforcer (e.g. foot shock) than does a nonpreexposed stimulus. This retarded conditioning to the preexposed as compared to the nonpreexposed stimulus, is latent inhibition (LI). LI is considered to index the capacity of organisms to ignore stimuli that predict no significant consequences, and can be demonstrated in a variety of classical and instrumental

The neural substrates of LI: initial data

A survey of the data on neural substrates of LI in 1990 [110] revealed the following. The noradrenergic system clearly played no role in this phenomenon. The same conclusion was made in regard to the cholinergic system, albeit on the basis of scarce data. Drug studies indicated a critical role for the dopaminergic system, since LI was shown to be disrupted by the DA releaser amphetamine and facilitated by the DA blocker haloperidol 17, 89, 100, 101, 103, 105, 105a, 106. Importantly, both of

The switching model

On the basis of the above data, the switching model of the neural substrates of LI was proposed [110]. At the time of the formulation of the switching model, most theoretical accounts of LI focused primarily on processes occurring during the nonreinforced stimulus preexposure, and the central debate surrounding the LI phenomenon concerned the precise nature of such processes 64, 6680a84, 85106a. The switching model accepted the general position that some kind of predictive relationship between

The neural substrates of LI: update

During the last 5 years, the understanding of the neural substrates of LI has been extended considerably.

Summary: the switching model refined

The data collected since the 1990 survey on the neural substrates of LI are consistent with the scheme outlined by the switching model. Lesion and intra-accumbens injections studies support the proposition that the NAC is a critical component of the neural circuitry underlying LI, and allow a more precise characterization of this circuitry. Drug studies, while consistent with the predictions of the switching model, raise interesting issues regarding the mechanisms of dopaminergic involvement in

Acknowledgements

Research in Tel-Aviv was supported by grants from the Israel Ministry of Science and the Commission of the European Community, and from the Israel Academy of Sciences Basic Research Fund; research in Zurich was supported by grants from the Swiss National Science Foundation. We thank our anonymous reviewers for constructive comments.

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