How Are Synapses Born? A Functional and Molecular View of the Role of the Wnt Signaling Pathway

Abstract

Synaptic transmission is a dynamic process that requires precise regulation. Early in life, we must be able to forge appropriate connections (add and remove) to control our behavior. Neurons must recognize appropriate targets, and external soluble factors that activate specific signaling cascades provide the regulation needed to achieve this goal. Wnt signaling has been implicated in several forms of synaptic plasticity, including functional and structural changes associated with brain development. The analysis of synapses from an electrophysiological perspective allows us to characterize the functional role of cellular signaling pathways involved in brain development. The application of quantal theory to principles of developmental plasticity offers the possibility of dissecting the function of structural changes associated with the birth of new synapses as well as the maturation of immature silent synapses. Here, we focus on electrophysiological and molecular evidence that the Wnt signaling pathway regulates glutamatergic synaptic transmission, specifically N-methyl-d-aspartate receptors (NMDARs), to control the birth of new synapses. We also focus on the role of Wnts in the conversion of silent synapses into functional synapses.

Exosomes promote axon outgrowth by engaging the Wnt-Planar Cell Polarity pathway

“…Wnts, including Wnt5a, Wnt7a and Wnt7b can promote axon elongation, neurogenesis and axon guidance, respectively, via the PCP pathway (Salinas, 2012; Bonansco et al ., 2022). As exosomes are known to carry Wnts (Routledge & Scholpp, 2019; Gross, 2021; Mittermeier & Virshup, 2022), we next explored whether the presence of Wnt ligands in isolated exosomes could contribute to the observed outgrowth of neurites.…”

“…Wnts are lipid-modified secreted glycoproteins that act as morphogens to regulate processes during embryonic development including cell proliferation and fate, polarity and migration (Willert & Nusse, 2012; Nusse & Clevers, 2017; Steinhart & Angers, 2018; Mittermeier & Virshup, 2022; Rim et al , 2022). In neurons, Wnts are known to modulate dendritogenesis, axon guidance and remodelling, synaptogenesis, synaptic plasticity and differentiation (Salinas, 2012; Bonansco et al , 2022). In mammals, there are 19 Wnts that bind to different classes of cell surface receptors and trigger diverse cellular responses (Rim et al ., 2022).…”

The mechanistic effects of acupuncture in rodent neurodegenerative disease models: a literature review

“…In neurodegenerative disorders, two vital processes related to the glutamatergic system have been reported, one is the excessive accumulation of glutamic acid (Glu) causing neuronal swelling and membrane integrity destruction, hence leading to movement disorders ( Hirschberg et al, 2022 ) and cognitive impairment ( Conway, 2020 ); another is the imbalance between synaptic and extrasynaptic glutamatergic receptors ( Babaei, 2021 ), including the N-methyl-D-aspartate (NMDA) receptors that induce excitatory postsynaptic potential (EPSP), and the aminomethylphosphonic acid (AMPA) receptors that facilitate the formation of late long-term potentiation (L-LTP) ( Bonansco et al, 2023 ; Figure 1 ).…”

Exploring the properties and potential of the neural extracellular matrix for next‐generation regenerative therapies

“…For example, collagens or FN undergo fragmentation due to the increased protease activity in the extracellular milieu, and the accumulation of advanced glycation end products leads to aberrant protein cross-linking in the ECM network, both of which affect cell sensitivity to environmental stimuli (Kular et al, 2014;Mutalik & Gupton, 2021;Rebelo et al, 2022;Scott & Panin, 2014). Additionally, changes in protein folding (Bonansco et al, 2023;Bondy & Lee, 1993;Cerpa et al, 2008;Chopra et al, 2019;Christopherson et al, 2005;Dono, 2003;Emsley & Hagg, 2003;Glasgow et al, 2021;Godbout & Johnson, 2004;Gregorio et al, 2018;Günther et al, 2005;Gutekunst et al, 2010;Hubert et al, 2009;Kowia nski et al, 2018;Lovero et al, 2015;Melrose et al, 2021;Monavarfeshani et al, 2017;Nguyen et al, 2020;Pintér et al, 2020;Pochon et al, 1997;Roszkowska et al, 2016;Seppänen et al, 2006;Shimazu et al, 2006;Song & Dityatev, 2018;Su et al, 2017;Xu et al, 2010;Yoo et al, 2017) and (b) aging (Chandra et al, 2022;Clarke et al, 2018;Ewald, 2020b;Godbout & Johnson, 2004;Kular et al, 2014;Nguyen et al, 2020;Nguyen et al, 2021;…”

“…Matrisome changes during CNS development, aging, injury, and disease. The graphs show some examples of changes in the expression of different ECM components observed during (a) development/maturation (Bonansco et al, 2023; Bondy & Lee, 1993; Carulli & Verhaagen, 2021; Cerpa et al, 2008; Chopra et al, 2019; Christopherson et al, 2005; Dono, 2003; Emsley & Hagg, 2003; Glasgow et al, 2021; Godbout & Johnson, 2004; Gregorio et al, 2018; Günther et al, 2005; Gutekunst et al, 2010; Hubert et al, 2009; Kowiański et al, 2018; Lovero et al, 2015; Melrose et al, 2021; Monavarfeshani et al, 2017; Nguyen et al, 2020; Pintér et al, 2020; Pochon et al, 1997; Roszkowska et al, 2016; Seppänen et al, 2006; Shimazu et al, 2006; Song & Dityatev, 2018; Su et al, 2017; Xu et al, 2010; Yoo et al, 2017) and (b) aging (Chandra et al, 2022; Clarke et al, 2018; Ewald, 2020b; Godbout & Johnson, 2004; Kular et al, 2014; Nguyen et al, 2020; Nguyen et al, 2021; Piekarz et al, 2020; Porcher et al, 2021; Reichwald et al, 2009; Shobin et al, 2017; Silva‐Vargas et al, 2016; Végh et al, 2014; Wang et al, 2020; Yin et al, 2016) of the CNS, as well as (c) in spinal cord injury (SCI), and (d) neurodegenerative disorders (NDD) such as AD (Berzin et al, 2000; Cheng et al, 2009; Downs et al, 2022; Hondius et al, 2016; Kalaria & Pax, 1995; Lendvai et al, 2013; Lorenzl et al, 2003; Lorenzl et al, 2004; Muenchhoff et al, 2014…”