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

Abstract Background Although cortical neurons are generated during embryogenesis, they mature postnatally, acquiring their characteristic electrophysiological properties and expressing specific molecular markers that define their cellular identity. In this regard, it has been proposed that some genes associated with neurodevelopmental disorders may regulate key functions during postnatal development, including the receptor tyrosine phosphatase Ptprd. We have previously demonstrated that loss of Ptprd promotes increased embryonic glutamatergic neurogenesis that persists into adulthood, affecting synaptic activity in the cerebral cortex and consequently, inducing autistic-like behaviors in 3-month-old Ptprd −/− animals. However, whether loss of Ptprd alters cortical neuronal populations and synaptic function during postnatal cortical development remains unknown. Results Here, we asked whether loss of Ptprd alters the number and function of excitatory and inhibitory neurons in the somatosensory cortex of Ptprd −/− animals during postnatal development. As expected, at postnatal day 21, Ptprd −/− mice showed an increased density of glutamatergic neurons positive for the markers Tbr1 and Satb2. However, opposite to what has been described in 3-month-old Ptprd −/− animals, the density of parvalbumin- and somatostatin-positive inhibitory neurons was reduced. However, biochemical analyses revealed increased expression of the inhibitory markers Gad67 and Vgat, together with elevated cortical GABA levels and increased density of Gad67-positive neurons in the somatosensory cortex. In addition, electrophysiological recordings revealed alterations in synaptic transmission in Ptprd −/− mice compared to wild-type littermates. Conclusions Together, these findings suggest that loss of Ptprd alters molecular and functional neuronal features associated with postnatal cortical circuit formation.