Table 2.
Roles of neuropeptides in cerebellar physiology and pathophysiology.
| Cerebellar Development | Neuronal Excitability, Synaptic Transmission, and Synaptic Plasticity |
Molecular, Circuital and Behavioral Phenotype |
|
|---|---|---|---|
| BDNF | Survival, migration, maturation, and arborization of GrCs ↑ [21,22,23,24,25,26] Survival of PCs ↑ [36] CF synapse elimination ↑ [27] Inhibitory synapse development ↑ [25,27] |
GrC and PC excitability ↑ [28] GABAergic transmission in PCs ↑↓ [29,30,31] Ionic plasticity ↑ [32] Paired-pulse facilitation ↑ [33] |
Neuroprotective effect ↑ [22,37] Neuroimmune modulation ↑ [38,39] Ataxic gait ↓ [23,36] |
| CRF | PC development ↑ [64,65] Presynaptic development in the cerebellar cortex ↑ [62,63] |
Glutamatergic neuron excitability in the interposed nucleus ↑ [43] PC excitability ↑ [47] LTD of PF–PC transmission ↑ [48] LTD of CF–PC transmission ↑ [49] LTP of CF–PC transmission ↑ [50] LTD between interneuron and PC ↓ [51] LTP of MF–GrC transmission ↑ [52] |
Motor control under challenging conditions ↑ [44] Motor performance ↑ [43] Motor learning ↓ [52,57] Ataxic symptoms ↓ [43] |
| Angiotensin II | IO–cerebellar pathway development ↑ [73] Neurite outgrowth and cell migration ↑ [74] |
PC excitability ↓ [75] GABAergic transmission in PCs ↑ [75] |
Aging- and senescence- related gene expression ↑ [70] Il-10 mRNA expression ↓ [76] Cyclooxygenase 2 expression ↑ [77] Proinflammatory effect ↑ [77] Astrocyte mitosis ↑ [77] Systemic oxytocin levels ↑ [80] |
| NPY | Cerebellar volume ↑ [89] GrC survival ↑ [89] |
BDNF levels ↑ [89] Anti-inflammatory effect ↑ [89] Mutant ataxin-3 aggregates ↓ [89] Motor coordination ↑ [89,90] |
|
| Orexin | CN excitability ↑ [98,102] Vestibular nuclear complex excitability ↑ [99] PC excitability ↑ [100] |
Cerebellar theta oscillations ↑ [101] The timing of TEC ↑ [101] Motor performance during a motor challenge ↑ [99] Arterial blood flow redistribution ↑ [100] Anxiolytic effect ↑ [102] |
|
| TRH | Migration and differentiation of GrCs ↑ [109] Dendritogenesis and neuritogenesis of PCs ↑ [109,110] Synaptogenesis ↑ [109] |
Neuronal excitability in the cerebellar cortex ↓ [112] Neuronal excitability in the interposed nucleus ↑ [108] LTD of PF–PC transmission ↑ [113,114] |
Bdnf mRNA levels ↑ [117] Glucose uptake ↑ [117] Motor coordination ↑ [114] Motor learning ↑ [113,114] Ataxic symptoms ↓ [115,116,117,118,119,120] |
| Oxytocin | Synaptic adhesion molecule ↑ [140] Cerebellum-putamen connectivity ↓ [131] Cerebellum-posterior cingulate cortex connectivity ↑ [132] |
||
| Secretin | Survival and arborization of PCs ↑ [143] Survival and maturation of GrC ↑ [143] Anti-apoptotic effects [147] |
GABAergic transmission in PCs ↑ [145,148,149] | The acquisition phase of DEC ↑ [150,151] Motor coordination ↑ [146] Motor learning ↑ [146] Autistic-like behaviors ↓ [152,153] |
Note: “↑” indicates positively regulated by the corresponding neuropeptides, “↓” indicates negatively regulated, and “↑↓” indicates regulated bidirectionally through different downstream molecules. Abbreviations: DEC, delay eyeblink conditioning; TEC, trace eyeblink conditioning.