Propranolol Modulates Cerebellar Circuit Activity and Reduces Tremor

Tremor is the most common movement disorder. Several drugs reduce tremor severity, but no cures are available. Propranolol, a beta-adrenergic receptor blocker, is the leading treatment for tremor. However, the in vivo circuit mechanisms by which propranolol decreases tremor remain unclear. Here, we test whether propranolol modulates activity in the cerebellum, a key node in the tremor network. We investigated the effects of propranolol in healthy control mice and Car8(wdl/wdl) mice, which exhibit pathophysiological tremor and ataxia due to cerebellar dysfunction. Propranolol reduced physiological tremor in control mice and reduced pathophysiological tremor in Car8(wdl/wdl) mice to control levels. Open field and footprinting assays showed that propranolol did not correct ataxia in Car8(wdl/wdl) mice. In vivo recordings in awake mice revealed that propranolol modulates the spiking activity of control and Car8(wdl/wdl) Purkinje cells. Recordings in cerebellar nuclei neurons, the targets of Purkinje cells, also revealed altered activity in propranolol-treated control and Car8(wdl/wdl) mice. Next, we tested whether propranolol reduces tremor through beta(1) and beta(2) adrenergic receptors. Propranolol did not change tremor amplitude or cerebellar nuclei activity in beta(1) and beta(2) null mice or Car8(wdl/wdl) mice lacking beta(1) and beta(2) receptor function. These data show that propranolol can modulate cerebellar circuit activity through beta-adrenergic receptors and may contribute to tremor therapeutics.

Automated summary

This study examined the effects of propranolol on tremor and cerebellar circuit activity in mice. The results showed that propranolol can reduce both physiological and pathophysiological tremor by modulating the activity of Purkinje cells and cerebellar nuclei neurons. However, it did not have any effect on ataxia in mice with cerebellar dysfunction. These findings suggest that propranolol may be a potential therapeutic option for tremor, but further research is needed to fully understand its mechanisms of action.