title: Non-spatial pre-training in the water maze as a clinically relevant model for evaluating learning and memory in experimental TBI.
abstract: Explicit and implicit learning and memory networks exist where each network can facilitate or inhibit cognition. Clinical evidence suggests that implicit networks are relatively preserved after traumatic brain injury (TBI). Non-spatial pre-training (NSPT) in the Morris Water Maze (MWM) provides the necessary behavioral components to complete the task, while limiting the formation of spatial maps. Our study utilized NSPT in the MWM to assess implicit and explicit learning and memory system deficits in the controlled cortical impact (CCI) model of TBI. 76 adult male Sprague-Dawley rats were divided: CCI vs. sham surgery, NSPT vs. No-NSPT, and cued vs. non-cued groups. NSPT occurred for 4d prior to surgery (dynamic hidden platform location, extra-maze cues covered, static pool entry point). Acquisition (d14-18), Probe/Visible Platform (d19), and Reversal (d20-21) trials were conducted with or without extra-maze cues. Novel time allocation and search strategy selection metrics were utilized. Results indicated implicit and explicit learning/memory networks are distinguishable in the MWM. In the cued condition, NSPT reduced thigmotaxis, improved place learning, and largely eliminated the apparent injury-induced deficits typically observed between untrained CCI and sham rats. However, among NSPT groups, incorporation of cues into search strategy selection for CCI rats was relatively impaired compared to shams. Non-cued condition performance showed sham/NSPT and CCI/NSPT rats perform similarly, suggesting implicit memory networks are largely intact 2weeks after CCI. Place learning differences between CCI/NSPT and sham/NSPT rats more accurately reflect spatial deficits in our CCI model compared to untrained controls. These data suggest NSPT as a clinically relevant construct for evaluating potential neurorestorative and neuroprotective therapies. These findings also support development of non-spatial cognitive training paradigms for evaluating rehabilitation relevant combination therapies.
authors.affiliation: University of Pittsburgh Department of Physical Medicine and Rehabilitation, 3471 Fifth Ave, Suite 201, Pittsburgh, PA 15213, United States; University of Pittsburgh Safar Center for Resuscitation Research, 3434 Fifth Ave, Pittsburgh, PA 15260, United States. Electronic address: wagnerak@upmc.edu.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Wagner
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Brayer
authors.forename: Max
authors.initials: M
authors.lastname: Hurwitz
authors.forename: Christian
authors.initials: C
authors.lastname: Niyonkuru
authors.forename: Huichao
authors.initials: H
authors.lastname: Zou
authors.forename: Michelle
authors.initials: M
authors.lastname: Failla
authors.forename: Patricia
authors.initials: P
authors.lastname: Arenth
authors.forename: Mioara D
authors.initials: MD
authors.lastname: Manole
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Skidmore
authors.forename: Edda
authors.initials: E
authors.lastname: Thiels
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000523:psychology* / Q000534:rehabilitation; D002540:Cerebral Cortex / Q000293:injuries; D004195:Disease Models, Animal; D007858:Learning / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000523:psychology* / Q000534:rehabilitation; D009043:Motor Activity / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: Controlled cortical impact; Implicit memory; Spatial memory; Thigmotaxis; Traumatic brain injury; Water maze