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© The Author 2017. Background: The ventral subiculum is known to be activated by the presentation of novel stressors. It has been hypothesized that neuronal ensembles at the ventral aspect of the hippocampal formation are involved in context-dependent processing and can guide the learning of appropriate action selections in response to threatening contexts. Artificial activation of the ventral subiculum can excite medium spiny neurons of the nucleus accumbens and can increase the excitability of mesolimbic dopamine neurons via a polysynaptic pathway through the basal ganglia. However, it remains unknown whether this circuit can be activated by aversive experience, and if so, whether ventral subiculum engages nucleus accumbens monosynaptically. Methods: To address this, the retrograde tracer fluorogold was used in rats to label neurons projecting to the caudomedial nucleus accumbens. One to 2 weeks later, the same rats were exposed to psychogenic stress (i.e., acute restraint in a novel test room) or served as nonhandled controls, followed by dual immunocytochemical localization of retrogradely transported tracer and nuclear Fos. Results: Compared with controls, rats exposed to psychogenic stress displayed more fluorogold-positive ventral subiculum neurons that were double-labeled for Fos. Conclusion: This study establishes that the direct pathway from ventral subiculum to the caudomedial nucleus accumbens is activated by stressful experience.

Clinical observations, postmortem work, and neuroimaging have fostered hypotheses on the etiology, pathology, psychology, and progression of schizophrenia. However, animal models are indispensable tools for testing and expanding these hypotheses rigorously. Here we review the methylazoxymethanol (MAM)-17 neurodevelopmental animal model of schizophrenia in which gross brain abnormalities observed in schizophrenia can be reliably mimicked by exposure to MAM in the rat on gestational day 17. In establishing the validity of this model, we summarize the rationale for approaching schizophrenia as a neurodevelopmental disorder, for using the MAM compound, and the schizophrenia-like abnormalities that the model reproduces. Work in this model has already led to the generation of unifying hypotheses on network dysfunction in schizophrenia, especially the relationship between anomalous hippocampal activity and dopamine dysregulation. Looking forward, the MAM-17 is an important animal model in which the critical neurodevelopmental events underlying the adolescent onset of this disorder may be elucidated and novel treatments may be tested and compared with currently available antipsychotics.

Previous studies, predominantly in experimental animals, have suggested the presence of a differentiation of function across the hippocampal formation. In rodents, ventral regions are thought to be involved in emotional behavior while dorsal regions mediate cognitive or spatial processes. Using a combination of modeling the co-occurrence of significant activations across thousands of neuroimaging experiments and subsequent data-driven clustering of these data we were able to provide evidence of distinct subregions within a region corresponding to the human subiculum, a critical hub within the hippocampal formation. This connectivity-based model consists of a bilateral anterior region, as well as separate posterior and intermediate regions on each hemisphere. Functional connectivity assessed both by meta-analytic and resting fMRI approaches revealed that more anterior regions were more strongly connected to the default mode network, and more posterior regions were more strongly connected to 'task positive' regions. In addition, our analysis revealed that the anterior subregion was functionally connected to the ventral striatum, midbrain and amygdala, a circuit that is central to models of stress and motivated behavior. Analysis of a behavioral taxonomy provided evidence for a role for each subregion in mnemonic processing, as well as implication of the anterior subregion in emotional and visual processing and the right posterior subregion in reward processing. These findings lend support to models which posit anterior-posterior differentiation of function within the human hippocampal formation and complement other early steps toward a comparative (cross-species) model of the region.