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

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.