Abstract
Schizophrenia is a chronic condition marked by impairments in memory, behavior, and motivation, often leading to challenges in decision-making. The development of schizophrenia is influenced by a combination of genetic susceptibility and environmental factors, including maternal immune activation (MIA). Maternal exposure to immunogens, or infections during pregnancy, better known as MIA, serves as a model for schizophrenia in animal studies.
These animal models, particularly for complex psychiatric conditions such as schizophrenia, offer crucial insights into the neurobiological underpinnings of the disorder. Such animal models recreate some of the alterations in brain function and behavior that are observed in schizophrenia, such as compromised memory. The hippocampus (HPC) plays a vital role in both encoding and retrieving memories while the entorhinal cortex (EC) is essential for the temporal association of memory and learning. Communication between the HPC and prefrontal cortex (PFC) is considered essential for behavioral selection from several alternatives.
In typical HPC studies, free-foraging behavior is often treated as a single, continuous unit. However, animals naturally alternate between two distinct movement regimes: slow, highly tortuous paths used to explore and exploit local resources, and faster, straighter paths used to transition between regions. This distinction becomes particularly relevant in models of schizophrenia.
Tortuosity, or the degree of twisting in a path, is used here as a behavioral proxy for how animals navigate and process space. In neuroscience, tortuosity can also reflect structural irregularities in
neural circuits — for example, more convoluted neuronal pathways may indicate disrupted or inefficient connectivity, which is a hallmark of schizophrenia.
In this study, we examined tortuosity in the exploratory behavior of rats exposed to MIA — a well-established model of schizophrenia risk. The aim was to determine whether MIA rats differ from controls in the structure of their movement paths, and whether these behavioral patterns correspond to changes in neural activity in the HPC and PFC. Increased or altered tortuosity in MIA animals may reflect disorganization in underlying brain circuits, providing insight into the cognitive and spatial processing deficits commonly seen in schizophrenia.
We examined spatial coding in the MIA model by looking at paths taken by animals with electrodes in the HPC and PFC and dividing each session into “search” and “transition” behavioral epochs. We found that just prior to transition between states there is communication between these regions that is absent from non-transition times. This suggests that these behavioral states are distinct, and that communication between HPC and PFC is associated with the switch in strategy.
Critically, an animal model of schizophrenia (the MIA model) causes a disruption in the communication between these regions at the transition points, which aligns with the concept that schizophrenia reflects a “binding” or integration of information deficit. Schizophrenia induces distortions in cognition and perception. We have uncovered new evidence that demonstrates that when animals change their behavioral regimes, there is a strong connection between the PFC and HPC, this is missing in MIA animals.
Finally, we also observed that schizophrenia induces changes in timing or the perception of time. This supports broader evidence that temporal processing abnormalities are a feature of the disorder and may relate to disrupted neural communication during cognitive transitions.