Sequential order spatial memory in male rats: Characteristics and impact of medial prefrontal cortex and hippocampus disruption.

Remembering an experience entails linking what happened, where the event transpired, and when it occurred. Most rodent hippocampal studies involve tests of spatial memory, but fewer investigate temporal and sequential order memory. Here we provide a demonstration of rats learning an aversive sequential order task using a radial arm water maze. Male rats learned a fixed sequence of up to seven spatial locations, with each decision session separated by a temporal delay. Rats relied on visuospatial cues and the number of times they had entered the maze for a given day in order to successfully perform the task. Behavioral patterns during asymptotic performance showed similarities to the serial-position effect, especially with regards to faster first choice latency. Rats at asymptotic performance were implanted with bilateral cannula in medial prefrontal cortex, dorsal, and ventral hippocampus. After re-training, we injected muscimol to temporarily disrupt targeted brain regions. While control rats made prospective errors, rats with mPFC muscimol exhibited more retrospective errors. Rats with hippocampal muscimol no longer exhibited a prospective bias and were at chance levels in their error choices. Taken together, our results suggest disruption of mPFC, but not the hippocampus, produced an error choice bias during an aversive sequential order spatial processing task.

Developmental Manipulation-Induced Changes in Cognitive Functioning.

Schizophrenia is a complex neurodevelopmental disorder with as-yet no identified cause. The use of animals has been critical to teasing apart the potential individual and intersecting roles of genetic and environmental risk factors in the development of schizophrenia. One way to recreate in animals the cognitive impairments seen in people with schizophrenia is to disrupt the prenatal or neonatal environment of laboratory rodent offspring. This approach can result in congruent perturbations in brain physiology, learning, memory, attention, and sensorimotor domains. Experimental designs utilizing such animal models have led to a greatly improved understanding of the biological mechanisms that could underlie the etiology and symptomology of schizophrenia, although there is still more to be discovered. The implementation of the Research and Domain Criterion (RDoC) has been critical in taking a more comprehensive approach to determining neural mechanisms underlying abnormal behavior in people with schizophrenia through its transdiagnostic approach toward targeting mechanisms rather than focusing on symptoms. Here, we describe several neurodevelopmental animal models of schizophrenia using an RDoC perspective approach. The implementation of animal models, combined with an RDoC framework, will bolster schizophrenia research leading to more targeted and likely effective therapeutic interventions resulting in better patient outcomes.

The effects of neonatal procedural pain and maternal isolation on hippocampal cell proliferation and reelin concentration in neonatal and adult male and female rats.

Preterm births accounted for over 10% of all U.S. live births in 2019 and the rate is rising. Neonatal stressors, especially procedural pain, experienced by preterm infants in the neonatal intensive care unit (NICU) have been associated with neurodevelopmental impairments. Parental care can alleviate stress during stressful or painful procedures; however, infants in the NICU often receive reduced parental care compared with their peers. Animal studies suggest that decreased maternal care similarly impairs neurodevelopment but also influences the effects of neonatal pain. It is important to mimic both stressors in animal models of neonatal stress exposure. In this study, researchers investigated the individual and combined impact of neonatal pain and maternal isolation on reelin protein levels and cellular proliferation in the hippocampal dentate gyrus of 8 days old and adult rats. Exposure to either stressor individually, but not both, increased reelin levels in the dentate gyrus of adult females without significantly altering reelin levels in adult males. However, cell proliferation levels at either age were unaffected by the early-life stressors. These results suggest that each early-life stressor has a unique effect on markers of brain development and more research is needed to further investigate their distinct influences.