Shuttle Box Assay as an Associative Learning Tool for Cognitive Assessment in Learning and Memory Studies using Adult Zebrafish

Hentig, James; Cloghessy, Kaylee; Hyde, David R.

doi:10.3791/62745

Cited by 4 publications

(11 citation statements)

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“…A shuttle box assay described by Truong et al [39] was modified to assess associative learning and memory [40]. The testing apparatus was a modified electrophoresis gel box with a width of 19 cm, length of 30 cm, height of 7.5 cm, and 45-degree ramps on each side leading to an elevated center platform that measured 19 cm × 15 cm, and the water level was set at 5 cm.…”

Section: Shuttle Box Assay Testing Apparatusmentioning

confidence: 99%

“…Learning was assessed in the shuttle box assay as previously described [40]. Briefly, undamaged control and blunt-force damaged fish (miTBI, moTBI, sTBI, n = 4, N = 3, 12 fish total) were individually placed into the shuttle box and examined at either 1, 2, 3, 4, 5, 6, 7, 14, or 28 dpi, with no fish being tested twice.…”

Section: Learningmentioning

confidence: 99%

“…Recall was assessed in the shuttle box assay as previously described [40]. Briefly, undamaged fish were individually placed into the shuttle box testing apparatus and tested as described under Learning.…”

Section: Immediate and Delayed Recallmentioning

confidence: 99%

“…Therefore, we tested associative learning and memory, higher-level cognitive tasks that are modulated in teleosts in part by the medialand lateral-dorsal pallium of the telencephalon [65,66], a region adjacent to our impact zone. To assess associative learning, we used a modified shuttle box assay [39], with a visual stimulus and an electrical shock as an adverse stimulus prompting learning by negative reinforcement [40]. Because the shuttle box assay relies on fish recognizing a visual stimulus, we first assessed survival of retinal neurons in sTBI fish.…”

Section: Timementioning

confidence: 99%

“…While humans with miTBI display little physiological pathologies, difficulties with short-term memory are a common feature [67]. We assessed whether our model recapitulated both immediate-and delayed recall of a learned behavior in undamaged and TBI treated fish using the shuttle box assay [40]. For immediate recall, the fish learned a behavior and then 4 h later were either undamaged or subjected to a TBI and then retested for the behavior learned 4 h before the TBI.…”

Section: Timementioning

confidence: 99%

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Zebrafish Blunt-Force TBI Induces Heterogenous Injury Pathologies That Mimic Human TBI and Responds with Sonic Hedgehog-Dependent Cell Proliferation across the Neuroaxis

et al. 2021

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Blunt-force traumatic brain injury (TBI) affects an increasing number of people worldwide as the range of injury severity and heterogeneity of injury pathologies have been recognized. Most current damage models utilize non-regenerative organisms, less common TBI mechanisms (penetrating, chemical, blast), and are limited in scalability of injury severity. We describe a scalable blunt-force TBI model that exhibits a wide range of human clinical pathologies and allows for the study of both injury pathology/progression and mechanisms of regenerative recovery. We modified the Marmarou weight drop model for adult zebrafish, which delivers a scalable injury spanning mild, moderate, and severe phenotypes. Following injury, zebrafish display a wide range of severity-dependent, injury-induced pathologies, including seizures, blood–brain barrier disruption, neuroinflammation, edema, vascular injury, decreased recovery rate, neuronal cell death, sensorimotor difficulties, and cognitive deficits. Injury-induced pathologies rapidly dissipate 4–7 days post-injury as robust cell proliferation is observed across the neuroaxis. In the cerebellum, proliferating nestin:GFP-positive cells originated from the cerebellar crest by 60 h post-injury, which then infiltrated into the granule cell layer and differentiated into neurons. Shh pathway genes increased in expression shortly following injury. Injection of the Shh agonist purmorphamine in undamaged fish induced a significant proliferative response, while the proliferative response was inhibited in injured fish treated with cyclopamine, a Shh antagonist. Collectively, these data demonstrate that a scalable blunt-force TBI to adult zebrafish results in many pathologies similar to human TBI, followed by recovery, and neuronal regeneration in a Shh-dependent manner.

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Section: Shuttle Box Assay Testing Apparatusmentioning

confidence: 99%

Section: Learningmentioning

confidence: 99%

Section: Immediate and Delayed Recallmentioning

confidence: 99%