Gating within limbic-cortical circuits and its alteration in a developmental disruption model of schizophrenia

• Published in: Clinical neuroscience research Vol. 3; no. 4; pp. 333 - 338
• Main Author: Grace, Anthony A.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-12-2003
• Subjects: Amygdala; Development; Gating; Hippocampus; Nucleus accumbens; Schizophrenia; Nucleus accumbens; Schizophrenia; Development; Amygdala; Gating; Hippocampus
• ISSN: 1566-2772
• DOI: 10.1016/j.cnr.2003.10.014

Schizophrenia is comprised of several symptom subtypes, including positive symptoms, negative symptoms, disorganization syndrome, and cognitive disturbances. Of these, evidence suggests that the positive symptoms are related to a dopaminergic hyperactivity within subcortical limbic regions, such as the nucleus accumbens. The accumbens itself receives overlapping inputs from several limbic areas, including the hippocampus subiculum and the amygdala, as well as afferents from the prefrontal cortex. Our studies show that the hippocampal input functions as a gate within the accumbens, modulating information flow along the prefrontal cortical-accumbens-pallidal-thalamic-prefrontal cortical loop. It is suggested that the hippocampal subiculum may exert a context-dependent gating within this loop, serving to keep an organism focused on a task. In contrast, the amygdala exerts a very brief, event-related gating that is likely related to affective states. It is this balance between hippocampal-driven focus on task and affect-mediated emotional drive that preserves normal function; a balance that is in part maintained by the dopamine system. This interaction was examined in a developmental disruption model of schizophrenia. In this model, a mitotoxin is administered to pregnant rats during gestational day 17. The adult offspring exhibit several neuroanatomical, behavioral, and pharmacological responses consistent with an animal model of schizophrenia. Moreover, in these animals, electrophysiological studies show that gating within the accumbens is driven primarily by the amygdala, rather than the hippocampus. If such a condition is present in schizophrenia, it would suggest that such patients would react to stimuli primarily based on affective valence, being easily distracted from tasks and goal-directed behaviors. Dopamine D2 antagonists would act to restore this balance by augmenting prefrontal cortical input while diminishing amygdala drive.