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Brain Sci. 2014, 4(2), 240-272; doi:10.3390/brainsci4020240

Spatial Working Memory Deficits in Male Rats Following Neonatal Hypoxic Ischemic Brain Injury Can Be Attenuated by Task Modifications

Behavioral Neuroscience Division, Department of Psychology, University of Connecticut, 406 Babbidge Road, Unit 1020, Storrs, CT 06269, USA
Division of Neonatology, Department of Pediatrics, University of Minnesota, 516 Delaware Street S.E. Minneapolis, MN 55454, USA
Department of Pediatrics, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA
Author to whom correspondence should be addressed.
Received: 22 December 2013 / Revised: 22 January 2014 / Accepted: 18 March 2014 / Published: 2 April 2014
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Hypoxia-ischemia (HI; reduction in blood/oxygen supply) is common in infants with serious birth complications, such as prolonged labor and cord prolapse, as well as in infants born prematurely (<37 weeks gestational age; GA). Most often, HI can lead to brain injury in the form of cortical and subcortical damage, as well as later cognitive/behavioral deficits. A common domain of impairment is working memory, which can be associated with heightened incidence of developmental disorders. To further characterize these clinical issues, the current investigation describes data from a rodent model of HI induced on postnatal (P)7, an age comparable to a term (GA 36–38) human. Specifically, we sought to assess working memory using an eight-arm radial water maze paradigm. Study 1 used a modified version of the paradigm, which requires a step-wise change in spatial memory via progressively more difficult tasks, as well as multiple daily trials for extra learning opportunity. Results were surprising and revealed a small HI deficit only for the final and most difficult condition, when a delay before test trial was introduced. Study 2 again used the modified radial arm maze, but presented the most difficult condition from the start, and only one daily test trial. Here, results were expected and revealed a robust and consistent HI deficit across all weeks. Combined results indicate that male HI rats can learn a difficult spatial working memory task if it is presented in a graded multi-trial format, but performance is poor and does not appear to remediate if the task is presented with high initial memory demand. Male HI rats in both studies displayed impulsive characteristics throughout testing evidenced as reduced choice latencies despite more errors. This aspect of behavioral results is consistent with impulsiveness as a core symptom of ADHD—a diagnosis common in children with HI insult. Overall findings suggest that task specific behavioral modifications are crucial to accommodating memory deficits in children suffering from cognitive impairments following neonatal HI. View Full-Text
Keywords: hypoxia ischemia; working memory; rodent model; eight-arm radial water maze; impulsivity hypoxia ischemia; working memory; rodent model; eight-arm radial water maze; impulsivity

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MDPI and ACS Style

Smith, A.L.; Hill, C.A.; Alexander, M.; Szalkowski, C.E.; Chrobak, J.J.; Rosenkrantz, T.S.; Fitch, R.H. Spatial Working Memory Deficits in Male Rats Following Neonatal Hypoxic Ischemic Brain Injury Can Be Attenuated by Task Modifications. Brain Sci. 2014, 4, 240-272.

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