Sonic Hedgehog Signaling and Hippocampal Neuroplasticity

Abstract

Sonic hedgehog (Shh) is a secreted protein that controls the patterning of neural progenitor cells, and their neuronal and glial progeny, during development. Emerging findings suggest that Shh also plays important roles in the formation and plasticity of neuronal circuits in the hippocampus, a brain region of fundamental importance in learning and memory. Shh mediates activity-dependent and injury-induced hippocampal neurogenesis. Activation of Shh receptors in the dendrites of hippocampal neurons engages a trans-neuronal signaling pathway that accelerates axon outgrowth and enhances glutamate release from presynaptic terminals. Impaired Shh signaling may contribute to the pathogenesis of several developmental and adult-onset neurological disorders that affect the hippocampus, suggesting a potential for therapeutic interventions that target Shh pathways.

Heterozygous mutation of Sonic Hedgehog receptor (Ptch) drives cerebellar overgrowth and sex-specifically alters hippocampal and cortical layer structure, activity, and social behavior in female mice

“…In addition to cerebellar dysregulation and MB tumorigenesis, altered hippocampal structures have been reported in male Ptch1 +/- adult mice (Antonelli et al, 2018). A finding consistent with SHH signaling also having potential roles in neurogenesis of hippocampal progenitors hippocampal (Yao et al, 2016).…”

Smoothened receptor Signaling regulates the developmental shift of GABA polarity in rat somatosensory cortex

“…Cortical neuronal network construction during postnatal period requires the depolarizing to hyperpolarizing shift of GABA to occur at a precise timing during maturation (Ben-Ari and Holmes, 2005;Wang and Kriegstein, 2009;Wu and Sun, 2015). Because Shh signaling plays a nodal role in brain development (Álvarez-Buylla and Ihrie, 2014;Delmotte et al, 2020;Yao et al, 2016), we investigated whether the manipulation of Smo activity will affect the onset of GABA excitatory/inhibitory postnatal shift at the network level. We performed field recordings of Multi Unit Activity (MUA) in acute cortical slices from control (GFP), Smo-CA and Smo-DN rats and measured the effect of bath application of the GABAAR agonist isoguvacine (10 µM) on their spiking activity at P14, P20 and P30.…”

Sonic hedgehog, Wnt, and brain‐derived neurotrophic factor cell signaling pathway crosstalk: potential therapy for depression

“…This pathway came to light during the genetic screening of Drosophila. It was later discovered that this pathway is involved in regulating the patterning of the brain and other body parts during embryogenesis and metamorphosis (Currie & Ingham, 1996;Lewis & Eisen, 2001;Shahi, Rey, & Castresana, 2012;Yao, Petralia, & Mattson, 2016). The precursor of Shh is a 45-kDa prepeptide that, through its autocatalytic activity, is cleaved into a 20-kDa N-terminal protein (Shh-N) and a 25-kDa C-terminal (Bumcrot & McMahon, 1995).…”