CPG15 regulates synapse stability in the developing and adult brain

Abstract

Use-dependent selection of optimal connections is a key feature of neural circuit development and, in the mature brain, underlies functional adaptation, such as is required for learning and memory. Activity patterns guide circuit refinement through selective stabilization or elimination of specific neuronal branches and synapses. The molecular signals that mediate activity-dependent synapse and arbor stabilization and maintenance remain elusive. We report that knockout of the activity-regulated gene cpg15 in mice delays developmental maturation of axonal and dendritic arbors visualized by anterograde tracing and diolistic labeling, respectively. Electrophysiology shows that synaptic maturation is also delayed, and electron microscopy confirms that many dendritic spines initially lack functional synaptic contacts. While circuits eventually develop, in vivo imaging reveals that spine maintenance is compromised in the adult, leading to a gradual attrition in spine numbers. Loss of cpg15 also results in poor learning. cpg15 knockout mice require more trails to learn, but once they learn, memories are retained. Our findings suggest that CPG15 acts to stabilize active synapses on dendritic spines, resulting in selective spine and arbor stabilization and synaptic maturation, and that synapse stabilization mediated by CPG15 is critical for efficient learning.

Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress

“…This may be particularly true for hippocampaldependent plasticity, given the enrichment of neuritin in this region. Our findings are consistent with recent data that neuritin regulates synapse stabilization, resulting in efficient learning (38). Together, the results suggest overlap of the cellular, neuroplasticity-related mechanisms underlying the antidepressant and memory-enhancing actions of neuritin.…”

MicroRNA-574 is involved in cognitive impairment in 5-month-old APP/PS1 mice through regulation of neuritin

“…Neuritin is a neurotrophic factor with the function of synaptic plasticity, and could affect on modulating neurite outgrowth and promoting neuritogenesis (Fujino et al, 2003). It was reported that Nrn1 plays an important role in regeneration and repair after nervous system impairment happened, like regulating synaptic plasticity (Fujino et al, 2011), promoting synaptic maturation and neuronal migration (Cantallops et al, 2000). Therefore, we focused on the miR-574 to test our hypothesis.…”

Expression and purification of recombinant human neuritin from Pichia pastoris and a partial analysis of its neurobiological activity in vitro

“…Neuritin exists in two forms: as a membrane protein that is anchored to the cell membrane via the GPI domain and as a soluble protein, which is generated via cleavage of the signal peptide. Previous studies have shown that neuritin participates in neuron synaptic transmission (Nedivi et al 2001), regulates synaptic plasticity (Fujino et al 2011;Leslie and Nedivi 2011;Loebrich and Nedivi 2009), inhibits cell degeneration and apoptosis (Putz et al 2005), stimulates neuronal migration (Antypa et al 2011;Zito et al 2014), and promotes the development and maturation of visual cortical neurons (Chen et al 2010;Corriveau et al 1999; Lee and Nedivi Yunhua Zhang and Shujun Zhang contributed equally to this work. .…”