Gene Loss Reshapes the Developing Mouse Cortex

Deleting the gene Ptprd disrupts the balance of excitatory and inhibitory neurons and alters synaptic function in the developing mouse somatosensory cortex, according to a research article published in Biological Research on 27 October 2026. The work is available as an early-access, peer-reviewed accepted manuscript that carries a permanent DOI and remains subject to further edits before the final version of record.

Ptprd encodes the receptor tyrosine phosphatase delta, a gene previously implicated in neurodevelopmental disorders by the same team. Their earlier experiments showed that loss of Ptprd increases embryonic glutamatergic neurogenesis, an excess that persists into adulthood and is associated with altered cortical synaptic activity and autistic-like behaviors in three-month-old Ptprd knockout animals. What remained unknown was whether the gene also shapes cortical neuronal populations and synaptic function during postnatal development, the period in which neurons generated during embryogenesis mature, acquire their characteristic electrophysiological properties, and express the molecular markers that define their identity.

To address this, the researchers compared the somatosensory cortex of Ptprd knockout mice with that of wild-type littermates at postnatal day 21. As expected from the earlier findings, the knockouts showed an increased density of glutamatergic neurons marked by the proteins Tbr1 and Satb2. The inhibitory side of the circuit told a more complicated story. The density of parvalbumin-positive and somatostatin-positive interneurons, two major classes of cortical inhibitory neurons, was reduced at this age, the opposite of the pattern previously described in three-month-old knockout animals.

Yet biochemical analyses of the same region pointed in a different direction. Expression of the inhibitory markers Gad67 and Vgat was increased, cortical levels of the neurotransmitter GABA were elevated, and the density of Gad67-positive neurons was higher in the knockout somatosensory cortex. Taken together with the reduced parvalbumin and somatostatin cell counts, these results suggest that loss of Ptprd changes the molecular composition of the inhibitory population during postnatal development rather than simply removing inhibitory neurons overall.

Function followed structure. Electrophysiological recordings from the knockout mice revealed alterations in synaptic transmission compared with their wild-type littermates, indicating that the molecular changes in neuronal populations are accompanied by measurable changes in how cortical circuits communicate at this developmental stage.

The authors conclude that loss of Ptprd alters molecular and functional neuronal features associated with postnatal cortical circuit formation. Because the findings come from a mouse model examined at a single postnatal age, and because the early-access version has not yet completed final editorial processing, the results should be read as evidence about this specific developmental window rather than as a complete account of how Ptprd shapes the cortex across the lifespan. The contrast with the three-month-old animals highlights that the effects of the gene loss are not static: the inhibitory deficits observed at day 21 differ from the pattern reported in adulthood, underscoring that cortical circuit changes in these mice evolve over development.

Subject of Research: How loss of the Ptprd gene alters neuronal populations and synaptic function in the developing mouse somatosensory cortex.

Article Title: Disruption of neuronal markers and synaptic function in the postnatal somatosensory cortex of Ptprd knockout mice

Article References: Cortés, B. I., Brito-Fernández, L., Delgado, R., Navarrete, M. P., Vargas-Zúñiga, M., Murgas, P., Riquelme, E. M., Renard, G. M., Cornejo, F., Nunez-Parra, A., & Cancino, G. I. (2026). Disruption of neuronal markers and synaptic function in the postnatal somatosensory cortex of Ptprd knockout mice. Biological Research. https://doi.org/10.1186/s40659-026-00731-9

Image Credits: AI Generated

DOI: 10.1186/s40659-026-00731-9

Keywords: Ptprd, somatosensory cortex, postnatal development, GABAergic interneurons, glutamatergic neurons, synaptic transmission, electrophysiology, neurodevelopmental disorders, knockout mice, cortical circuits, Disruption, neuronal