Abstract
Here, we investigate stimulus generalization in a cerebellar learning paradigm, called eyeblink conditioning. Mice were conditioned to close their eyes in response to a 10-kHz tone by repeatedly pairing this tone with an air puff to the eye 250 ms after tone onset. After 10 consecutive days of training, when mice showed reliable conditioned eyelid responses to the 10-kHz tone, we started to expose them to tones with other frequencies, ranging from 2 to 20 kHz. We found that mice had a strong generalization gradient, whereby the probability and amplitude of conditioned eyelid responses gradually decreases depending on the dissimilarity with the 10-kHz tone. Tones with frequencies closest to 10 kHz evoked the most and largest conditioned eyelid responses and each step away from the 10-kHz tone resulted in fewer and smaller conditioned responses (CRs). In addition, we found that tones with lower frequencies resulted in CRs that peaked earlier after tone onset compared with those to tones with higher frequencies. Together, our data show prominent generalization patterns in cerebellar learning. Since the known function of cerebellum is rapidly expanding from pure motor control to domains that include cognition, reward-learning, fear-learning, social function, and even addiction, our data imply generalization controlled by cerebellum in all these domains.
Highlights
Given the advance of transgenics and optogenetics (Boyden, 2015; Deisseroth, 2011; Navabpour et al, 2020), mice have become increasingly a popular animal model to study mechanisms underlying cerebellar learning (Alba, 1994; Albergaria et al, 2018; Gao et al., 2016; Heiney et al, 2014; Kloth et al, 2015; Zhang et al, 2019)
We calculated the conditioned responses (CRs) amplitude over the CR only trials and found a similar main effect of session (Figure 4E; Table 1; F(9,931)=8.14, p
We found that mice show a strong generalization of conditioned responses (CRs) in Pavlovian eyeblink conditioning using a tone as conditional stimulus
Summary
Given the advance of transgenics and optogenetics (Boyden, 2015; Deisseroth, 2011; Navabpour et al, 2020), mice have become increasingly a popular animal model to study mechanisms underlying cerebellar learning (Alba, 1994; Albergaria et al, 2018; Gao et al., 2016; Heiney et al, 2014; Kloth et al, 2015; Zhang et al, 2019). This holds for Pavlovian eyeblink conditioning, a behavioral test that allows for wide variations in parameter space, including those of onset, duration and intensity of both conditional and unconditional stimuli (Alba, 1994; Chettih et al, 2011). Stimulus generalization has probably been most extensively studied in the context of Pavlovian fear conditioning (Bang et al, 2008; Dymond et al, 2015; Hovland, 1937; Lissek et al, 2008; Meulders & Vlaeyen, 2013), showing that emotional and fight-or-flight responses can be triggered by stimuli other than the one used during acquisition training
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