Behavioral Core Experience
Dr. Kokiko-Cochran has extensive experience in rodent behavioral testing (and is a big fan of quotes!). As a post-doc she managed a Rodent Behavioral Core for four years at the Lerner Research Institute, part of the Cleveland Clinic. In this position, Dr. Kokiko-Cochran offered consultation services in experimental design and assisted with data collection, analysis, and interpretation.
Dr. Kokiko-Cochran took over as the Director of the Rodent Behavioral Core at Ohio State in June 2019. This is a Core Service supported by a P30 grant. She continues to assist investigators in generating quality behavioral data. Dr. Kokiko-Cochran aims to create an optimal testing environment where data analysis is stratified to evaluate within and between trial effects. For example, incorporating additional learning indices and search strategy analysis may aide in interpretation of spatial memory impairments over time. Some of Dr. Kokiko-Cochran's previous work supports this strategy.
Dr. Kokiko-Cochran took over as the Director of the Rodent Behavioral Core at Ohio State in June 2019. This is a Core Service supported by a P30 grant. She continues to assist investigators in generating quality behavioral data. Dr. Kokiko-Cochran aims to create an optimal testing environment where data analysis is stratified to evaluate within and between trial effects. For example, incorporating additional learning indices and search strategy analysis may aide in interpretation of spatial memory impairments over time. Some of Dr. Kokiko-Cochran's previous work supports this strategy.
Assessment of Cognitive Function in the Water Maze Task: Maximizing Data Collection and Analysis
in Animal Models of Brain Injury
Whiting & Kokiko-Cochran, 2016
Methods in Molecular Biology, 1462:553-71
Fig. 2 Illustration of difference search strategies adopted by TBI injured (panel A) and sham control animals (panel B) by trial 4, day 2 of water maze acquisition training. Despite the dramatically different search paths through the maze, the latency to the platform for these two animals was nearly identical (TBI panel A = 85 seconds; sham control panel B = 88 seconds), illustrating the importance of using additional dependent variables such as proximity and thigmotaxia.
Acquisition Index
The acquisition index is simply a measure of within-day learning, averaged across all days of training, so that in a multiple day water maze protocol the acquisition index would be:
...where tF and tL are the first and last trials of the day (d), respectively, and k is the number of days of training in the water maze. This index will often reveal differences in within-day learning between sham and injured animals, as sham animals tend to show much greater within-day improvements relative to injured animals.
Savings Index
Another important question when analyzing behavioral data from any multiple-day learning and memory task is whether animals can transfer what is learned in 1 day of training to subsequent training sessions. A savings index is thus an indirect measure of memory consolidation, storage, and retrieval processes, although it alone cannot distinguish among the three. In a multiple-day water maze task, the savings index would be:
...where the difference is computed between the last trial of a given day and the first trial of the subsequent day, averaged across all days.
Altered Neuroinflammation and Behavior after Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease
Kokiko-Cochran et al., 2016
Journal of Neurotrauma, 33(7), 625-640
The current study examined the acute and chronic macrophage response to TBI in the presence or absence of accumulating Aβ. Subsequent correlations were identified between macrophage alterations and long-term neurodegeneration and behavioral impairment. The R1.40 mouse model of cerebral amyloidosis contains a full genomic copy of the human APP gene with a familial AD mutation and develops age-related appearance of Aβ pathology at 12 months of age as well as earlier biochemical, neuropathological, and behavioral features of human AD. Surprisingly, the inflammatory reaction to TBI was markedly reduced at acute time points in R1.40 mice, which then displayed enhanced brain cavitation along with a unique pattern of cognitive impairment 4 months later.
The water maze is an integrative task that necessitates coordinate deployment of encoding, consolidation, storage, and retrieval, all of which are distinct memory processes. To better assess these behavioral components, we used the learning indices described above. The acquisition index, which measures within-day learning, in non-Tg TBI mice was less than one suggesting that the time to reach the goal platform was similar between trial 1 and trial 4 within any given memory testing day. Surprisingly, the acquisition index in R1.40 TBI mice averaged around 13 and was significantly higher than brain-injured non-Tg mice (t = 3.373, p < 0.01, Fig. 7E). This finding demonstrates that R1.40 TBI mice show tremendous improvement in performance between trial 1 and trial 4 within any given memory testing day.
Next, we used the savings index, which quantifies how much learned information is transferred or “saved” across days and provides an indirect measure of memory consolidation. The savings index in non-Tg TBI mice averaged around two, indicating that there was only slight improvement from one day to the next in the latency to reach the goal platform. Interestingly, the savings index in R1.40 TBI mice averaged around negative six, suggesting that performance significantly worsened from one day to the next (t = 2.147, p < 0.05, Fig. 7F). Together, these data demonstrate that non-Tg and R1.40 TBI mice maintain unique profiles of within and between day learning in the water maze task even though average latency to reach the platform was similar. R1.40 mice display a deficit in transferring information from one day to the next but are able to overcome this deficit by quickly improving their performance within each day, providing further evidence of a time-dependent impairment in cognitive performance.
Next, we used the savings index, which quantifies how much learned information is transferred or “saved” across days and provides an indirect measure of memory consolidation. The savings index in non-Tg TBI mice averaged around two, indicating that there was only slight improvement from one day to the next in the latency to reach the goal platform. Interestingly, the savings index in R1.40 TBI mice averaged around negative six, suggesting that performance significantly worsened from one day to the next (t = 2.147, p < 0.05, Fig. 7F). Together, these data demonstrate that non-Tg and R1.40 TBI mice maintain unique profiles of within and between day learning in the water maze task even though average latency to reach the platform was similar. R1.40 mice display a deficit in transferring information from one day to the next but are able to overcome this deficit by quickly improving their performance within each day, providing further evidence of a time-dependent impairment in cognitive performance.
Fig. 7. Traumatic brain injury (TBI) induces time dependent changes in motor and cognitive function. (A) Mean latency to fall from the rotating rod was shorter in TBI mice at all post-injury time points compared to shams regardless of genotype. No between genotype differences in rotarod performance were detected in sham and TBI mice (n = 12–14/group). (B) No significant differences between groups in average spontaneous alternation in the y maze. R1.40 TBI mice showed a significant reduction in percent spontaneous alternation between arms from 7 days post-injury (DPI) to 90 DPI. (C) Average total arm entries were similar between TBI groups; however, sham mice demonstrated a significant reduction in arm entries over time (n = 12–14/group). (D) A significant interaction effect between injury and genotype was detected in latency to reach the hidden platform at 120 DPI (n = 12–14/group). (E) Average acquisition index shows that latency to reach the platform significantly decreases within a testing day in R1.40 compared with non-Tg mice. (F) Average savings index shows that latency to reach the platform significantly increases between testing days in R1.40 compared with Non-Tg mice. Error bars indicate standard error of the mean. Main effect of injury: *, p < 0.05; ***, p < 0.001; Interaction effect: ++, p < 0.01; +++, p < 0.001.
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