Divergent Representation and Processing of Task Cues in Sensory and Prefrontal Cortices of Preterm-Born Mice

Abstract

Preterm birth is a leading risk factor for atypicalities in cognitive and sensory processing, but it is unclear how prematurity impacts circuits that support these functions. To address this, we trained adult male and female mice born a day early (preterm mice) on a visual discrimination task and found that they fail to achieve high levels of performance due to increased responding to the non-rewarded cue (false alarms). While the representation of task cues measured with in vivo electrophysiology is intact in the primary visual cortex (V1) of trained preterm mice, the representation of the non-rewarded cue is significantly weaker in regular spiking, putative pyramidal neurons in the prefrontal cortex (PFC), a brain area that mediates response inhibition. Responses to both task cues are blunted in electrophysiologically and optogenetically identified fast-spiking Parvalbumin interneurons in preterm mice, indicating impaired processing of task cues in their PFC. Indeed, single trial neuronal responses evoked by the non-rewarded cue predict the behavioral outcome more accurately in term than in preterm mice. Similar cue representation and processing is present in the PFC of adolescent term-born mice, suggesting that preterm birth impedes prefrontal maturation. Surprisingly, environmental enrichment, a well-established paradigm that promotes sensory maturation, fails to improve the performance of preterm mice. Altogether, our study describes the long-term impact of preterm birth on prefrontal and visual circuits and suggests a limited capacity of early interventions for reducing the risk of cognitive deficits after preterm birth.