Abstract

The cerebellum in transgenic mice expressing pseudorabies virus immediate-early protein IE180 (TgIE96) was substantially diminished in size, and its histoarchitecture was severely disorganized, resulting in severe ataxia. TgIE96 mice can therefore be used as an experimental model to study the involvement of cerebellar circuits in different learning tasks. The performance of three-month-old TgIE96 mice was studied in various behavioral tests, including associative learning (classical eyeblink conditioning), object recognition, spatial orientation (water maze), startle response and prepulse inhibition, and passive avoidance, and compared with that of wild-type mice. Wild-type and TgIE96 mice presented similar reflexively evoked eyeblinks, and acquired classical conditioned eyelid responses with similar learning curves for both trace and delay conditioning paradigms. The two groups of mice also had similar performances during the object recognition test. However, they showed significant differences for the other three tests included in this study. Although both groups of animals were capable of swimming, TgIE96 mice failed to learn the water maze task during the allowed time. The startle response to a severe tone was similar in both control and TgIE96 mice, but the latter were unable to produce a significant prepulse inhibition. TgIE96 mice also presented evident deficits for the proper accomplishment of a passive avoidance test. These results suggest that the cerebellum is not indispensable for the performance of classical eyeblink conditioning and for object recognition tasks, but seems to be necessary for the proper performance of water maze, prepulse inhibition, and passive avoidance tests.

Highlights

  • Pseudorabies virus is classified into the genus Varicellovirus of the subfamily Alphaherpesvirinae [1]

  • Systematic differences in reflexively evoked eyelid responses would not preclude the possibility of examining whether blink responses may be acquired in an associative task, putative differences in the acquisition process between both groups of animals could be ascribed to the learning process and not to any performance deficit

  • General remarks According to the present results, TgIE96 mice have marked deficits in spatial learning as shown by their poor performance in the water maze test

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Summary

Introduction

Pseudorabies virus is classified into the genus Varicellovirus of the subfamily Alphaherpesvirinae [1]. This virus invades and spreads along the trigeminal pathway of neonatal pigs, i.e., the nasal mucosa, trigeminal ganglion, trigeminal nuclei, and their projection areas, such as the cerebellum and thalamus [2,3]. It causes severe neurological disorders in infected piglets, including nervous signs such as unbalanced stepping, trembling, staggering, and convulsions, and latent infection in surviving pigs. Pseudorabies virus is a highly neurotropic virus that causes neurological symptoms

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