LTD, RP, and Motor Learning

Abstract

Long-term depression (LTD) at excitatory synapses between parallel fibers and a Purkinje cell has been regarded as a critical cellular mechanism for motor learning. However, it was demonstrated that normal motor learning occurs under LTD suppression, suggesting that cerebellar plasticity mechanisms other than LTD also contribute to motor learning. One candidate for such plasticity is rebound potentiation (RP), which is long-term potentiation at inhibitory synapses between a stellate cell and a Purkinje cell. Both LTD and RP are induced by the increase in postsynaptic Ca(2+) concentration, and work to suppress the activity of a Purkinje cell. Thus, LTD and RP might work synergistically, and one might compensate defects of the other. RP induction is dependent on the interaction between GABAA receptor and GABAA receptor binding protein (GABARAP). Transgenic mice expressing a peptide which inhibits binding of GABARAP and GABAA receptor only in Purkinje cells show defects in both RP and adaptation of vestibulo-ocular reflex (VOR), a motor learning paradigm. However, another example of motor learning, adaptation of optokinetic response (OKR), is normal in the transgenic mice. Both VOR and OKR are reflex eye movements suppressing the slip of visual image on the retina during head movement. Previously, we reported that delphilin knockout mice show facilitated LTD induction and enhanced OKR adaptation, but we recently found that VOR adaptation was not enhanced in the knockout mice. These results together suggest that animals might use LTD and RP differently depending on motor learning tasks.

Differential regulations of vestibulo-ocular reflex and optokinetic response by β- and α2-adrenergic receptors in the cerebellar flocculus

“…Different contributions of LTD and RP to VOR and OKR adaptation have also been reported. In delphilin knockout mice, LTD is more easily induced than in wild-type mice and OKR adaptation is facilitated 10 , whereas VOR adaptation is not 11 . In RP-deficient transgenic mice, VOR adaptation is suppressed but OKR adaptation is not 8 .…”

“…Although the roles and regulatory neuronal pathways are similar between VOR and OKR, differential regulations of VOR and OKR by cerebellar synaptic plasticity mechanisms have been reported 8, 10, 11 . In addition, Faulstich et al .…”

Spinal microcircuits comprising dI3 interneurons are necessary for motor functional recovery following spinal cord transection

“…In other words, the re-acquisition of locomotion can be considered to be a low level form of motor learning, in which repeated activity leads to sustained changes in the central nervous system such that spinal circuits below the site of a lesion can produce locomotor activity in the absence of descending motor commands. In this light, it is therefore instructive to consider that circuits that mediate short-term adaptation are those that lead to long-term learning through various mechanisms (Hirano et al, 2016). We have previously shown that dI3 INs mediate short-term adaptation in regulating paw grasp in response to changing sensory stimulation (Bui et al, 2013).…”

Flexible and adaptive processes in speech perception

“…For example, in other domains, supervised learning is thought to result from long-term depression of parallel fiber-purkinje cell synapses (and long-term potentiation of parallel fiber and interneuron synapses) in the cerebellum (De Zeeuw et al, 1998;Ito, 2002;Jorntell, 2016;Hirano, Yamazaki & Nakamura, 2016), implicating γ-aminobutyric acid (GABA-ergic) dependent plasticity (e. g., Lee et al, 2015). Phosphorylation mechanisms that are dependent on sustained protein kinase activation may regulate AMPA receptor internalization and long-term depression in the cerebellum, as suggested recent neurobiological computational (Gallimore et al, 2016).…”