The infliction of war and military aggression upon children must be considered a violation of their basic human rights and can have a persistent impact on their physical and mental health and well-being, with long-term consequences for their development. Given the recent events in Ukraine with millions on the flight, this scoping policy editorial aims to help guide mental health support for young victims of war through an overview of the direct and indirect burden of war on child mental health. We highlight multilevel, need-oriented, and trauma-informed approaches to regaining and sustaining outer and inner security after exposure to the trauma of war. The impact of war on children is tremendous and pervasive, with multiple implications, including immediate stress-responses, increased risk for specific mental disorders, distress from forced separation from parents, and fear for personal and family’s safety. Thus, the experiences that children have to endure during and as consequence of war are in harsh contrast to their developmental needs and their right to grow up in a physically and emotionally safe and predictable environment. Mental health and psychosocial interventions for war-affected children should be multileveled, specifically targeted towards the child’s needs, trauma-informed, and strength- and resilience-oriented. Immediate supportive interventions should focus on providing basic physical and emotional resources and care to children to help them regain both external safety and inner security. Screening and assessment of the child’s mental health burden and resources are indicated to inform targeted interventions. A growing body of research demonstrates the efficacy and effectiveness of evidence-based interventions, from lower-threshold and short-term group-based interventions to individualized evidence-based psychotherapy. Obviously, supporting children also entails enabling and supporting parents in the care for their children, as well as providing post-migration infrastructures and social environments that foster mental health. Health systems in Europe should undertake a concerted effort to meet the increased mental health needs of refugee children directly exposed and traumatized by the recent war in Ukraine as well as to those indirectly affected by these events. The current crisis necessitates political action and collective engagement, together with guidelines by mental health professionals on how to reduce harm in children either directly or indirectly exposed to war and its consequences.

The striatum is the largest nucleus of the basal ganglia, and is crucially involved in motor control. Striatal projection cells are medium-size spiny neurons (MSNs) and form functional GABAergic synapses with other MSNs through their axon collaterals. A subpopulation of MSNs also release substance P (SP), but its role in MSN-MSN communication is unknown. We studied this issue in rat brain slices, in the presence of antagonists for GABA, acetylcholine, dopamine, and opioid receptors; under these conditions, whole-cell paired recordings from MSNs (located Ͻ100 m apart) revealed that, in 31/137 (23%) pairs, a burst of five spikes in a MSN caused significant facilitation (14.2 Ϯ 8.9%) of evoked glutamatergic responses in the other MSN. Reciprocal facilitation of glutamatergic responses was present in 4 of these pairs. These facilitatory effects were maximal when spikes preceded glutamatergic responses by 100 ms, and were completely blocked by the NK1 receptor antagonist L-732,138. Furthermore, in 31/57 (54%) MSNs, a burst of 5 antidromic stimuli delivered to MSN axons in the globus pallidus significantly potentiated glutamatergic responses evoked 250 or 500 ms later by stimulation of the corpus callosum. These effects were larger at 250 than 500 ms intervals, were completely blocked by L-732,138, and facilitated spike generation. These data demonstrate that MSNs facilitate glutamatergic inputs to neighboring MSNs through spike-released SP acting on NK1 receptors. The current view that MSNs form inhibitory networks characterized by competitive dynamics will have to be updated to incorporate the fact that groups of MSNs interact in an excitatory manner.

N-methyl-D-aspartate receptors (NMDAR) are pivotal for synaptic plasticity and memory formation. Conventional NMDAR consist of heterotetrameric structures composed of GluN1 and GluN2 subunits. A third subunit, GluN3, can also assemble with NMDAR subunits giving a remarkable modification of their heteromeric structure, forming a “nonconventional” NMDAR. As a consequence, the stoichiometry and kinetic properties of the receptors are dramatically changed. Among the GluN3 family, the GluN3A subunit has been the focus of a large amount of studies during recent years. These studies reveal that GluN3A is transiently expressed during development and could play a role in the fine tuning of neuronal networks as well as associated diseases. Moreover, GluN3A distribution outside the postsynaptic densities, including perisynaptic astrocytes, places it at a strategic position to play an important role in the interactions between neurons and glial cells. This review highlights GluN3A properties and addresses its role in neurophysiology and associated pathologies.

Synaptic rearrangements during critical periods of postnatal brain development rely on the correct formation, strengthening, and elimination of synapses and associated dendritic spines to form functional networks. The correct balance of these processes is thought to be regulated by synapse-specific changes in the subunit composition of NMDA-type glutamate receptors (NMDARs). Among these, the nonconventional NMDAR subunit GluN3A has been suggested to play a role as a molecular brake in synaptic maturation. We tested here this hypothesis using confocal time-lapse imaging in rat hippocampal organotypic slices and assessed the role of GluN3A-containing NMDARs on spine dynamics. We found that overexpressing GluN3A reduced spine density over time, increased spine elimination, and decreased spine stability. The effect of GluN3A overexpression could be further enhanced by using an endocytosis-deficient GluN3A mutant and reproduced by silencing the adaptor protein PACSIN1, which prevents the endocytosis of endogenous GluN3A. Conversely, silencing of GluN3A reduced spine elimination and favored spine stability. Moreover, reexpression of GluN3A in more mature tissue reinstated an increased spine pruning and a low spine stability. Mechanistically, the decreased stability in GluN3A overexpressing neurons could be linked to a failure of plasticity-inducing protocols to selectively stabilize spines and was dependent on the ability of GluN3A to bind the postsynaptic scaffold GIT1. Together, these data provide strong evidence that GluN3A prevents the activitydependent stabilization of synapses thereby promoting spine pruning, and suggest that GluN3A expression operates as a molecular signal for controlling the extent and timing of synapse maturation.