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 memory. 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 2 weeks 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.

Longitudinal measures of cognition in the Ts65Dn mouse: Refining windows and defining modalities for therapeutic intervention in Down syndrome

“…Thigmotaxis was defined by continuous swimming along the periphery of the tank as previously described (Wagner et al, 2013). This behavior indicates a lack of focus on the task and is considered a confounding factor in the MWM test (Vorhees and Williams, 2006).…”

Developing a Clinically Relevant Model of Cognitive Training After Experimental Traumatic Brain Injury

“…1 However, similar relevant pre-clinical treatment paradigms do not exist. Based on previous work from this lab with implicit training pre-CCI, 9 we developed a cognitive training model for experimental TBI relevant to clinical cognitive rehabilitation paradigms. The goal for this initial study was to build an effective implicit cognitive training model as an exemplar from which to develop combination therapies, and to test specific learning, memory, and training constructs in relationship to histological and molecular analyses.…”

“…9 Time allocation (TA) in the pool periphery (peripheral-zone; 29% of total pool area) was recorded to quantify thigmotaxis. No portion of the escape platform was located in the peripheral-zone (Figure 1).…”

“…9 Swim strategies were characterized as spatial, nonspatial, or thigmotaxic. These broad categories were subdivided into seven more specific search strategies, 9 and representative strategies are provided (Figure 2). The percentage of runs for each trial type and primary strategy (Spatial/Non-Spatial/Thigmotaxis) was calculated and analyzed.…”

“…However, explicit feedback can impair the use of implicitly learned skills. 7,8 Our recent work used implicit pre-training in the Morris water maze (MWM) to dissect the cognitive components of behavioral deficits observed with place learning after experimental TBI 9 ; implicit learning/memory were relatively intact after experimental TBI, while explicit learning/memory were impaired. The data also suggested that implicit training after injury may be a viable method for improving new learning/memory after experimental TBI.…”