BMP-SMAD1 signaling regulates the balance of excitation and inhibition in the adult mouse neocortex. Neuronal networks in the mammalian neocortex maintain a balance of excitation and inhibition, essential for neuronal computation. Deviations from this balance are linked to neurodevelopmental disorders and epilepsy. The study identifies a signaling pathway in the adult mouse neocortex that is activated in response to increased neuronal network activity. BMP2, a growth factor, is upregulated in glutamatergic neurons and acts on parvalbumin-expressing (PV) interneurons through the transcription factor SMAD1, which controls glutamatergic synapse proteins and perineuronal nets. Disruption of BMP2-SMAD1 signaling in PV interneurons leads to reduced glutamatergic innervation, underdeveloped perineuronal nets, and decreased excitability, disrupting the excitation-inhibition balance and causing spontaneous seizures. BMP2-SMAD1 signaling is repurposed to stabilize cortical networks in the adult brain. Neuronal activity mobilizes BMP signaling, which is regulated by SMAD1 and affects synaptic proteins and perineuronal nets. BMP2-SMAD1 signaling regulates synaptic proteins and the innervation of PV interneurons, which are crucial for maintaining the excitation-inhibition balance. Loss of SMAD1 in PV interneurons reduces glutamatergic input and leads to a severe disruption of the cortical excitation-inhibition balance, resulting in hyperactivity and spontaneous seizures. The study highlights the role of BMP-SMAD1 signaling in maintaining the balance of excitation and inhibition in the adult neocortex.BMP-SMAD1 signaling regulates the balance of excitation and inhibition in the adult mouse neocortex. Neuronal networks in the mammalian neocortex maintain a balance of excitation and inhibition, essential for neuronal computation. Deviations from this balance are linked to neurodevelopmental disorders and epilepsy. The study identifies a signaling pathway in the adult mouse neocortex that is activated in response to increased neuronal network activity. BMP2, a growth factor, is upregulated in glutamatergic neurons and acts on parvalbumin-expressing (PV) interneurons through the transcription factor SMAD1, which controls glutamatergic synapse proteins and perineuronal nets. Disruption of BMP2-SMAD1 signaling in PV interneurons leads to reduced glutamatergic innervation, underdeveloped perineuronal nets, and decreased excitability, disrupting the excitation-inhibition balance and causing spontaneous seizures. BMP2-SMAD1 signaling is repurposed to stabilize cortical networks in the adult brain. Neuronal activity mobilizes BMP signaling, which is regulated by SMAD1 and affects synaptic proteins and perineuronal nets. BMP2-SMAD1 signaling regulates synaptic proteins and the innervation of PV interneurons, which are crucial for maintaining the excitation-inhibition balance. Loss of SMAD1 in PV interneurons reduces glutamatergic input and leads to a severe disruption of the cortical excitation-inhibition balance, resulting in hyperactivity and spontaneous seizures. The study highlights the role of BMP-SMAD1 signaling in maintaining the balance of excitation and inhibition in the adult neocortex.