Gaps between normative advancement and clinical response: the inclusion of the deaf community in Chilean public health.

Cognitive flexibility is often impaired in psychiatric disorders, yet how norepinephrine engages prefrontal network dynamics remains unclear. We investigate how global GluN2A deficiency affects LC–mPFC dynamics while accounting for potential systemic and developmental contributions. These findings show that global GluN2A deficiency disrupts noradrenergic induction of synchronized oscillatory activity and highlight 2-adrenergic pathways as a candidate therapeutic entry point for improving prefrontal network function. Importantly, our results suggest that functional deficits in global knock-out models must be interpreted within the context of compensatory structural changes in circuit architecture, such as hyperinnervation. Cognitive flexibility—the capacity to adjust behavior when contingencies change—depends on the integrity of prefrontal circuits and is disrupted in many neuropsychiatric disorders (). The medial prefrontal cortex (mPFC) receives dense noradrenergic input from the locus ceruleus (LC), which modulates excitability and helps coordinate cortical activity across behavioral states (; ). Phasic norepinephrine (NE) release can promote gamma-frequency synchronization and support task switching, mediated in part by α2-adrenergic receptors that stabilize recurrent activity through suppression of cAMP-dependent K conductances (; ). Although adrenergic mechanisms supporting attention and working memory are well defined (), how NE engages prefrontal network rhythms to support behavioral flexibility—and how this control fails in disease-relevant states—remains unclear. Dysregulated noradrenergic signaling within mPFC circuits has been implicated in cognitive inflexibility and neuropsychiatric vulnerability, motivating efforts to define how LC-derived NE recruits coordinated prefrontal dynamics. Mutations in GRIN2A, encoding the GluN2A subunit of NMDA receptors, are linked to cognitive rigidity and psychiatric vulnerability (). GluN2A-containing receptors govern synaptic maturation, temporal integration, and gamma-band synchrony during cognitively demanding states (; ). Noradrenergic and glutamatergic signaling converge on prefrontal pyramidal neurons to regulate network precision (), yet it is unknown whether GluN2A is required for NE to recruit synchronized activity patterns in mPFC. More broadly, LC and mPFC form a reciprocal circuit in which ascending neuromodulatory drive and descending cortical feedback jointly shape adaptive control, raising the possibility that GluN2A dysfunction destabilizes this loop.