Precise temporal control of sensorimotor coordination and adaptation is a fundamental basis of animal behavior. How different brain regions are involved in regulating the flexible temporal adaptation remains elusive. Here, we investigated the neuronal dynamics of the cerebellar interposed nucleus (IpN) and the medial prefrontal cortex (mPFC) neurons during temporal adaptation between delay eyeblink conditioning (DEC) and trace eyeblink conditioning (TEC). When mice were trained for either DEC or TEC and subsequently subjected to a new paradigm, their conditioned responses (CRs) adapted virtually instantaneously. Changes in the activity of the IpN neurons related to CR timing were prominent during DEC-to-TEC adaptation, but less so during TEC-to-DEC adaptation. In contrast, mPFC neurons could rapidly alter their modulation patterns during both adaptation paradigms. Accordingly, silencing the mPFC completely blocked the adaptation of CR timing. These results illustrate how cerebral and cerebellar mechanisms may play different roles during adaptive control of associative motor timing.
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