Table 1.

mTOR role and signaling components in the different stages of the CNS.

Stage	Processes	Identified signaling pathway components	Reference
Early CNS development
	Check point for the progression of differentiation	Ngn2, Pax6	Fishwick et al., 2010
	NSCs size and switching cap-dependent translation on and off	S6K1/2, 4E-BPs	Hartman et al., 2013
	Neural progenitor development	GSK3, Sox2	Ka et al., 2014
	Soma size increase and axon extension	T3, BDNF, TrkB	Westerholz et al., 2013
	Impaired growth and interneuron migration and decreased survival	Tsc1	Fu et al., 2012
	Proliferation, survival, and neuronal differentiation	IGF1, TGFβ	Wahane et al. (2014)
	Neurite outgrowth	5HT7R, Erk, Cdk5, Cdc42 MeCbl Insulin, RAPTOR, RICTOR	Speranza et al., 2015 Okada et al., 2011 Urbanska et al., 2012
	Impaired neurite outgrowth and cell viability	Sirt1	Guo et al., 2011
	Oligodendrocyte development	Cannabinoid receptors Myelinating proteins: MBP, Tmem10, MOG, PLP	Gómez et al., 2011 Zou et al., 2014
Adult CNS
• Hippocampus	Neurogenesis	Ezh2	Zhang et al., 2014
	Dendritic spine formation	IR, Rac Disc1	Lee et al., 2011 Kim et al., 2009
	Late-stage plasticity	HuD, CaMKIIα	Sosanya et al., 2015
	Enhanced spatial cognitive function	TrkA, ERK	Zhou et al., 2014
	Learning and memory performance	S6K1, 4E-BP1	Qi et al., 2010; Su et al., 2015
	Memory consolidation	Estrogen and progesterone, TrkB, ERK calpain BDNF, GluR1	Fortress et al., 2013; Briz and Baudry, 2014; Orr et al., 2012; Slipczuk et al., 2009
	Long-term memory, protein synthesis	Circadian oscillations eIF4E, 4E-BP1, S6, ERK1/2 CB1R	Saraf et al., 2014 Puighermanal et al., 2009
	Learning and memory deficits	DISC1	Zhou et al., 2013
• Striatum	Motor learning consolidation	S6K1, 4E-BP	Bergeron et al., 2014
• Amygdala	Memory consolidation of fear memory	KLK8, FKBP51	Jobim et al., 2012a,b; Pedroso et al., 2013 Hadamitzky et al., 2014 Mac Callum et al., 2014
• Medial prefrontal cortex	Trace fear memory Antidepressant effects	S6K1	Sui et al., 2008 Dwyer et al., 2015
• Auditory cortex	Memory consolidation for the discrimination of auditory stimuli	Dopaminergic activity	Schicknick et al., 2008
CNS aging
	Increase lifespan	Decreased p-mTOR/mTOR	Triplett et al., 2015
	Decreased rate of degradation	Rag-Ragulator complex	Yu et al., 2014
	Decreased cognitive function	BDNF, Akt	Yang et al., 2014
	Learning and memory dysfunction	p62, S6K1	Dong et al., 2015a,b
	Alterations in histone methylation levels	H3K27me3, H3R2me2, H3K79me3 H3K4me2	Gong et al., 2015
	Enhanced autophagy, synaptic plasticity	CREB, decreased mTOR	Liu et al., 2015
	Better memory performance	LARS2, FASTKD40	Ramanan et al., 2015
	Adult neurogenesis	S6, EGF	Romine et al., 2015 Paliouras et al., 2012
	Circadian control of aging	BMAL1	Khapre et al., 2014