Presentation
Acute And Chronic Learning Impairment Following Seizures In Larval Zebrafish
Experimental Biology 2022
(2022)
Abstract
Early-life seizures (ELS) can disrupt brain development, often leading to cognitive impairments in humans and rodents. Here, we investigated whether seizures in larval zebrafish (Danio rerio) lead to acute and long-term learning deficits. Based on ELS studies in rodents, we hypothesized that seizures in larval zebrafish would impair their performance in declarative memory tasks. To test this, we induced seizures in larval zebrafish using pentylenetetrazole (PTZ), which causes behavioral and electrical seizures in zebrafish. We modified the existing PTZ seizure model, exposing zebrafish to PTZ daily from 5-7 days post-fertilization (dpf). We then compared later-life learning through short-term memory tasks that lacked external punishment or motivation and focused on conscious recognition and interest in novel stimuli. To test learning and memory acutely after seizures, we used the visual lateralization novel object recognition (VLNOR) test, based on the novel object recognition test frequently used in rodents. Zebrafish show asymmetries in the use of left (LES) and right eye systems (RES), and will initially use LES to observe novel objects and RES to view familiar objects. We found that, when tested for recall of a previously novel object one hour after initially viewing it, 12-14 dpf unhandled controls (UC group) reached a statistically significant majority of RES approaches by the end of the 8-minute recall test (p=0.048). The PTZ group did not, and trended towards a significant decrease from 50% in the first 2 minute bin of the recall test (p=0.054). Taken together, these data indicate that the PTZ fish were not able to recall a previously viewed object, and when the object was reintroduced 1 hour later, responded as if the object were novel. We next used a y-maze task to assess memory 3 months after seizures. In this task, fish had to recall the novel arm of the maze 90 minutes after being removed from the maze. The PTZ group spent significantly less time in the novel arm of the y-maze during the recall test compared to their UC clutchmates (mean % time in novel arm +/- SE = 44.0+/-3.2 for UC, 29.7+/-2.1 for PTZ; p=0.002 by t-test). Furthermore, our preliminary molecular studies show distinct expression profiles of synaptic plasticity genes between PTZ and UC groups by qPCR. Taken together, these results imply that inducing seizures in larval zebrafish leads to both acute and chronic learning and memory impairments. These findings expand the behavioral characterization of the larval zebrafish seizure model, strengthening the power of this model for researching the cognitive consequences of ELS.
Disciplines
Publication Date
April, 2022
Location
Philadelphia, PA
DOI
https://doi.org/10.1096/fasebj.2022.36.S1.R3885
Citation Information
Alfonsina Ramon, Nicole Belamorich, Faisha Salami, Hasimran Singh, et al.. "Acute And Chronic Learning Impairment Following Seizures In Larval Zebrafish" Experimental Biology 2022 (2022) Available at: http://works.bepress.com/jocelyn-lippman-bell/11/