Deep Cerebellar Nuclei Play an Important Role in Two-Tone Discrimination on Delay Eyeblink Conditioning in C57BL/6 Mice

Toshiro Sakamoto,Shogo Endo,Thomas Boraud

doi:10.1371/journal.pone.0059880

Toshiro Sakamoto, Shogo Endo + Show 1 more

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https://doi.org/10.1371/journal.pone.0059880

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Abstract

Previous studies have shown that deep cerebellar nuclei (DCN)-lesioned mice develop conditioned responses (CR) on delay eyeblink conditioning when a salient tone conditioned stimulus (CS) is used, which suggests that the cerebellum potentially plays a role in more complicated cognitive functions. In the present study, we examined the role of DCN in tone frequency discrimination in the delay eyeblink-conditioning paradigm. In the first experiment, DCN-lesioned and sham-operated mice were subjected to standard simple eyeblink conditioning under low-frequency tone CS (LCS: 1 kHz, 80 dB) or high-frequency tone CS (HCS: 10 kHz, 70 dB) conditions. DCN-lesioned mice developed CR in both CS conditions as well as sham-operated mice. In the second experiment, DCN-lesioned and sham-operated mice were subjected to two-tone discrimination tasks, with LCS+ (or HCS+) paired with unconditioned stimulus (US), and HCS− (or LCS−) without US. CR% in sham-operated mice increased in LCS+ (or HCS+) trials, regardless of tone frequency of CS, but not in HCS− (or LCS−) trials. The results indicate that sham-operated mice can discriminate between LCS+ and HCS− (or HCS+ and LCS−). In contrast, DCN-lesioned mice showed high CR% in not only LCS+ (or HCS+) trials but also HCS− (or LCS−) trials. The results indicate that DCN lesions impair the discrimination between tone frequency in eyeblink conditioning. Our results suggest that the cerebellum plays a pivotal role in the discrimination of tone frequency.

Highlights

Eyeblink conditioning is one form of associative learning, which develops by the paired presentation of a neutral conditioned stimulus (CS), such as tones, and an unconditioned stimulus (US), such as electric shocks and air puffs
Performances of deep cerebellar nuclei (DCN) lesioned mice did not relate the lesion size and placement among mice in both Exp.1 and Exp.2. Both DCN-lesioned and sham-operated mice acquired the conditioned responses (CR) in delay eyeblink conditioning under salient CS conditions (10 kHz, 70dB) [15]. These results indicated that the cerebellum is not critical for simple eyeblink conditioning when the salient CS is used
The results indicate that DCN is not so critical for standard eyeblink conditioning

Summary

Introduction

Eyeblink conditioning is one form of associative learning, which develops by the paired presentation of a neutral conditioned stimulus (CS), such as tones, and an unconditioned stimulus (US), such as electric shocks and air puffs. Recent developments and the availability of a variety of genetically-modified mice have made it possible to examine the role of certain neuronal cells and target molecules in the cerebellum that are involved in eyeblink conditioning. We revealed that mouse DCN play important roles in delay eyeblink conditioning with the low intensity CS [16], but not with high intensity CS [15]. We revealed the essential role of the lateral amygdala for mouse eyeblink conditioning in response to high intensity CS [15]. Our findings suggest that the cerebellum is not involved in the acquisition of eyeblink conditioning when the high intensity CS is used in combination with the US of an electric shock

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