Research in our lab is focused on the study of behavioral consequences of injury or disruption of typical developmental processes in the young brain. To address this topic, we employ various rodent models of developmental brain injury/disruption, and then follow subjects as they develop by studying their behavioral and cognitive abilities.
For example, we can study the behavioral effects of focal disruption to the rat cortex during the critical period of neuromigration. Disruptions during this key period lead to focal brain anomalies similar to those seen in various developmental disabilities in humans. Such anomalies can be induced by freezing lesions to the rat cortical plate on postnatal day 1 (leading to ectopias and microgyria, as seen in human dyslexic brains). Other models derive from disruptions of early brain development through embryonic manipulation (RNAi; RNA interference or knock-down) of genes known to be associated with developmental disabilities. Importantly, many of these genes are also critical to neuronal migration and/or other aspects of early neurodevelopment. More recent development have made available mouse lines in which genes have been engineered for systemic or neurally regionalized deletion (using Lox-Cre methods), or for temporally conditional knock-out (allowing exploration of timing in genetic regulation). We can use these models to investigate the long term behavioral correlates of these disruptions, to determine what systems are affected -- as well as how such impairments might be averted or ameliorated.
Another model we use investigates early hypoxic-ischemic injury -- similar to that seen in premature and very low birthweight infants, or in term babies suffering hypoxic injuries due to birth complications. Again, we examine the later behavioral correlates of these early injuries in rodents, as well as the relationship between neuropathologic and behavioral outcomes. Moreover, this model is particularly amenable to the study of interventions such as treatment with neuroprotectants (erythropoietin, caffeine) or cooling (whole-head or body hypothermia).
Using such models, we can also examine the influence of modulating variables -- such as the effects of age and sex (male vs female) on behavioral response to early brain injury.
Behavioral measures include assessments of rapid auditory processing; this testing can begin in rodents as young as 30 days of age. Auditory processing assessments are used based on strong evidence that early processing of rapidly changing auditory information is correlated with, and predictive of, language development in humans. Additional behavioral tests include assessments of spatial navigation (e.g., Morris Water Maze), working memory (e.g., radial arm maze), non-spatial learning and memory (e.g., T-maze, operant conditioning and learning), motor earning (e.g., rotarod), exploration and locomotion (open-field), anxiety (Plus-maze), aggression (test-tube task), and social behaviors (e.g., 3-chamber social task, vocalizations).
