Expression and functional implications of secretin in cerebellar cortex

Abstract

Secretin was widely accepted as one gastrointestinal peptide hormone, but in recent decades, its expression in the brain has been gradually revealed. We showed prominent expression of secretin peptide in cerebellar Purkinje neurons. Site-specific knockout of secretin gene identified its indispensable role in maintaining normal motor coordination and motor learning functions of mice. Such behavioral paradigms can be explained from electrophysiological and development aspects. In physiological study, secretin could facilitate inhibitory transmission between interneurons and Purkinje cells. For a developmental explanation, the knockout of secretin gene led to altered migration of cerebellar granular precursor cells, plus higher apoptosis level at early postnatal stage. Moreover, Purkinje cell formation and dendritic arborization showed deficits with endogenous secretin deprivation. These anatomic features were consistent with retard occurrence of sensorimotor reflex in secretin knockout mice. Overall speaking, our previous studies established the role of secretin in regulating cerebellar motor functions via maintaining normal synaptic transmission and lamination of cerebellar cortical neurons.