2024 Theses Doctoral

In vivo Studies of Postnatal Physiologic and Pathologic Neural Network Activity Development

Ma, Liang

Mature neural network functions and their activity correlates are not innate properties of the neonatal brain. Neural network oscillations mediating cognitive processes such as long-term memory require postnatal developmental emergence. Early cortical activity patterns are discontinuous and often externally driven, whereas later in development mature, complex, continuous and internally generated patterns emerge.

However, the postnatal time course of this transition of cortical dynamics is poorly characterized. Specific cognitive processes such as memory consolidation and reconsolidation are differentially regulated by precise temporal coupling of hippocampal and cortical oscillations, including sleep spindles, hippocampal sharp wave-ripples, and cortical ripples. Yet the developmental emergence of cortical ripples and its coupling patterns remain unknown, in part due to challenges in recording from distributed brain regions in small immature animals. Furthermore, neurodevelopmental disorders often disrupt activity maturation, but large-scale investigations of pathological network development are lacking.

We first conducted in vivo electrophysiology in mice during early development, and identified an evolutionarily conserved developmental trajectory of large-scale cortical dynamics. Next, we developed and validated high-density conformable neural probes (NeuroShanks) for targeting deep brain regions in developing animals. We then used NeuroShanks to investigate ripple-band oscillations in the developing hippocampal-cortical network, and proposed a conceptual model of network maturation. Finally, we extended our methods to uncover early dysregulation and pathological maturation in a pediatric mouse model of genetic epilepsy.