Consequences at adulthood of transient inactivation of the parahippocampal and prefrontal regions during early development: new insights from a disconnection animal model for schizophrenia

Abstract

The psychic disintegration characteristic of schizophrenia is thought to result from a defective connectivity, of neurodevelopmental origin, between several integrative brain regions. The parahippocampal region and the prefrontal cortex are described as the main regions affected in schizophrenia. Interestingly, latent inhibition (LI) has been found to be reduced in patients with schizophrenia, and the existence of a dopaminergic dysfunction is also generally well accepted in this disorder. In the present review, we have integrated behavioral and neurochemical data obtained in a LI protocol involving adult rats subjected to neonatal functional inactivation of the entorhinal cortex, the ventral subiculum or the prefrontal cortex. The data discussed suggest a subtle and transient functional blockade during early development of the aforementioned brain regions is sufficient to induce schizophrenia-related behavioral and dopaminergic abnormalities in adulthood. In summary, these results support the view that our conceptual and methodological approach, based on functional disconnections, is valid for modeling some aspects of the pathophysiology of schizophrenia from a neurodevelopmental perspective.

Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults

“…2). Notably, several studies report on the developmental impact on parahippocampal regions (Grateron et al 2003; Meyer and Louilot 2014). Interestingly, it has been suggested that a subtle and transient functional blockade during early developmental periods is sufficient to induce schizophrenia-like behavioral and dopaminergic abnormalities in adulthood (Meyer and Louilot 2014; Peterschmitt et al 2007).…”

A Neuroanatomical Signature for Schizophrenia Across Different Ethnic Groups

“…This analysis focused on 22 regions of interest that are implicated in contemporary animal 19 and human 11 , 20–24 models of schizophrenia; see table 2 for complete list. The identification of these regions was carried out using the Automated Anatomical Labeling atlas as implemented in PickAtlas software ( ).…”

“…As we preprocessed and analysed each dataset independently, using ethnic-specific templates, our investigation can be thought of as a series of replication studies across 4 independent datasets. We hypothesised that the 4 groups would show consistent neuroanatomical reductions in specific prefrontal, parietal, and limbic regions that are implicated in existing animal 19 and human 11 , 20–24 models of schizophrenia. This would provide evidence for a neuroanatomical signature of schizophrenia expressed above and beyond ethnic differences in incidence and clinical expression.…”

Tcf4 transgenic female mice display delayed adaptation in an auditory latent inhibition paradigm

“…The phenomenon is observed across species and involves selective attention [8]. LI belongs to the most common behavioral paradigms used in SZ studies [10]. LI, similarly to reversal learning, requires a shift between stimulus-outcome associations, and previous learning of one association hampers the shift to the new one [8].…”

“…Yet, opposing opinions exist as some SZaffected individuals display normal LI [10,[17][18][19]. Nevertheless, there is an increasing interest in studying LI as an endophenotype in the context of SZ, and LI deficits have been proposed as a suitable tool to model deficient attention in at least some forms of the disease [8,16,[20][21][22].…”