Attention Deficit-Hyperactivity Disorder (ADHD): From Abnormal Behavior to Impairment in Synaptic Plasticity

SIMPLE SUMMARY: Attention deficit-hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high incidence in children and adolescents characterized by hyperactivity, impulsivity, and inattention. Neuroanatomical anomalies such as the volume reduction in the neocortex and hippocampus and the abnormal dendritic spine pruning during postnatal development are shared by several neuropsychiatric diseases such as schizophrenia, autism spectrum disorder and ADHD. This review presents recent evidence focused on the molecular mechanisms involved in dendritic spine remodeling in the context of synaptic plasticity and learning. The impairment in synaptic plasticity, working memory and spine phenotype in a murine model of ADHD are also discussed. ABSTRACT: Attention deficit-hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high incidence in children and adolescents characterized by motor hyperactivity, impulsivity, and inattention. Magnetic resonance imaging (MRI) has revealed that neuroanatomical abnormalities such as the volume reduction in the neocortex and hippocampus are shared by several neuropsychiatric diseases such as schizophrenia, autism spectrum disorder and ADHD. Furthermore, the abnormal development and postnatal pruning of dendritic spines of neocortical neurons in schizophrenia, autism spectrum disorder and intellectual disability are well documented. Dendritic spines are dynamic structures exhibiting Hebbian and homeostatic plasticity that triggers intracellular cascades involving glutamate receptors, calcium influx and remodeling of the F-actin network. The long-term potentiation (LTP)-induced insertion of postsynaptic glutamate receptors is associated with the enlargement of spine heads and long-term depression (LTD) with spine shrinkage. Using a murine model of ADHD, a delay in dendritic spines’ maturation in CA1 hippocampal neurons correlated with impaired working memory and hippocampal LTP has recently reported. The aim of this review is to summarize recent evidence that has emerged from studies focused on the neuroanatomical and genetic features found in ADHD patients as well as reports from animal models describing the molecular structure and remodeling of dendritic spines.