The long-term impact of neonatal hypoxic-ischemic brain injury on neural dynamics in deep-layer retrosplenial cortex and hippocampus in mice

Perinatal hypoxic-ischemia (HI) often results in hypoxic-ischemic encephalopathy (HIE), a major cause of neonatal mortality and long-term neurodevelopmental deficits. While motor and cognitive impairments are common, the underlying neuronal mechanisms remain poorly understood. Using a mouse model of neonatal HI, we examined long-term effects on neuronal activity in the retrosplenial cortex (RSC) and hippocampus through simultaneous electrophysiological recordings in freely moving adults. HI mice showed a significant reduction in neurons recorded per tetrode, and remaining pyramidal neurons in the ipsilateral hemisphere exhibited abnormal bursting, synchrony, and pathological spike-field coupling to theta-alpha oscillations. These neural abnormalities coincided with impaired motor learning performance across training sessions. Our findings reveal persistent disruptions in firing patterns and RSC-hippocampus communication, providing insight into long-term motor learning deficits at the single-neuron level, following neonatal HI brain injury.