Neural substrates of latent inhibition: the switching model

Latent inhibition (LI) refers to decrement in conditioning to a stimulus as a result of its prior nonreinforced preexposure. It is a robust phenomenon that has been demonstrated in a variety of classical and instrumental conditioning procedures and in many mammalian species, including humans. The development of LI is considered to reflect decreased associability of, or attention to, stimuli that predict no significant outcome. The fact that LI is considered to be a reflection of attentional processes has become of increasing importance to neuroscientists who see LI as a convenient tool for measuring the effects of drug treatments and lesions on attention. The present article surveys the data on brain systems, which have been studied in regard to their involvement in LI. These are reviewed and discussed separately in sections on noradrenergic, cholinergic, dopaminergic, serotonergic, and septo-hippocampal manipulations. On the basis of these data, it is concluded that the neural substrates of LI include the mesolimbic dopaminergic system, the mesolimbic serotonergic system, and the hippocampus. It is proposed that the preexposed stimulus loses its capacity to affect behavior in conditioning, even though it predicts reinforcement, because the hippocampus inhibits the switching mechanism of the nucleus accumbens via the subiculum-accumbens pathway. This action of the hippocampus is modulated by the mesolimbic serotonergic system via its interactions with the hippocampal or mesolimbic dopaminergic systems, or both.