Abstract
Classical eyeblink conditioning is an experimental model widely used for the study of the neuronal mechanisms underlying the acquisition of new motor and cognitive skills. There are two principal interpretations of the role of the cerebellum in the learning of eyelid conditioned responses (CRs). One considers that the cerebellum is the place where this learning is acquired and stored, while the second suggests that the cerebellum is mostly involved in the proper performance of acquired CRs, implying that there must be other brain areas involved in the learning process. We checked the timing of cerebellar interpositus nucleus (IPN) neurons’ firing rate with eyelid CRs in both wild-type (WT) and Lurcher (a model of cerebellar cortex degeneration) mice. We used delay and trace conditioning paradigms. WT mice presented a better execution for delay vs. trace conditioning and also for these two paradigms than did Lurcher mice. IPN neurons were activated during CRs following the activation of the orbicularis oculi muscle. Firing patterns of IPN neurons were altered in Lurcher mice. In conclusion, the cerebellum seems to be mostly related with the performance of conditioned responses, rather than with their acquisition.
Highlights
Classical eyeblink conditioning is a well-known and accessible experimental model for the study of associative learning in mammals
Type A neurons were characterized by their activation by air-puff or tone presentations, with activation latencies of ≈10 ms for air-puff presentations, whereas type B neurons were characterized by their inactivation by the same stimuli (Fig. 1c,d)
The neural mechanisms underlying eyeblink conditioning–mostly the delay paradigm–have been delineated more completely than for any other type of mammalian learning, there are a number of critical issues that require further investigation[41]
Summary
Classical eyeblink conditioning is a well-known and accessible experimental model for the study of associative learning in mammals. Other studies propose that plastic changes underlying eyeblink conditioning are distributed across several cerebellar and extracerebellar regions, resulting in a network performance[9] Such hypothesis could be in accordance with those works that assign an important role in this type of associative learning to the motor[10] and the prefrontal[11,12,13] cortices, the hippocampus[14], or the amygdala[15]. Those experimental approaches used various techniques, ranging from the lesion of cerebellar structures to electrophysiological recordings of cerebellar cortical and nuclear neurons, as well as the use of mutant or genetically manipulated mice[16,17,18,19,20,21,22]. To study the putative relationships between the firing rate of IPN neurons and CRs, we have implemented automatic analysis software, capable of detecting fine timing correlations between them
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