Control of neuronal excitation-inhibition balance by BMP-SMAD1 signalling

Control of neuronal excitation-inhibition balance by BMP-SMAD1 signalling

17 April 2024 | Zeynep Okur1,4, Nadia Schlauri1,4, Vassilis Bitsikas1, Myrto Panopoulou1, Raul Ortiz1, Michaela Schwaiger2,3, Kajari Karmakar1,5, Dietmar Schreiner1 & Peter Scheiffele1,5
The study investigates the control of neuronal excitation-inhibition balance in the adult mouse neocortex through the BMP-SMAD1 signaling pathway. Increased neuronal network activity triggers the upregulation of BMP2 in pyramidal neurons, which activates SMAD1 in parvalbumin-expressing (PV) interneurons. SMAD1 regulates an array of glutamatergic synapse proteins and components of perineuronal nets (PNNs), affecting the innervation and excitability of PV interneurons. Disruption of BMP2-SMAD1 signaling in PV interneurons leads to reduced glutamatergic innervation, underdeveloped PNNs, and decreased excitability, ultimately disrupting the cortical excitation-inhibition balance. This impairment results in spontaneous epileptic seizures in mice. The findings suggest that developmental morphogen signaling is repurposed to stabilize cortical networks in the adult mammalian brain.The study investigates the control of neuronal excitation-inhibition balance in the adult mouse neocortex through the BMP-SMAD1 signaling pathway. Increased neuronal network activity triggers the upregulation of BMP2 in pyramidal neurons, which activates SMAD1 in parvalbumin-expressing (PV) interneurons. SMAD1 regulates an array of glutamatergic synapse proteins and components of perineuronal nets (PNNs), affecting the innervation and excitability of PV interneurons. Disruption of BMP2-SMAD1 signaling in PV interneurons leads to reduced glutamatergic innervation, underdeveloped PNNs, and decreased excitability, ultimately disrupting the cortical excitation-inhibition balance. This impairment results in spontaneous epileptic seizures in mice. The findings suggest that developmental morphogen signaling is repurposed to stabilize cortical networks in the adult mammalian brain.
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