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

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.

Keywords: attention deficit-hyperactivity disorder; dendritic spines; hippocampus; long-term potentiation; neurodevelopmental disorders; prenatal nicotine exposure model.

Figure 1

Schematic representation of intracellular pathways involved in the spine enlargement and shrinkage associated with high frequency stimulation (HFS) and low frequency stimulation (LFS) occurring after LTP and LTD, respectively. AMPAR: AMPA receptor; NMDAR: NMDA receptor; CaMKII: calcium/calmodulin-dependent protein kinase II; CaN: calcineurin; p-cofilin: phosphorylated cofilin. For details see the main text.