Losing balance: Kainate receptors and psychiatric disorders comorbidities

Cognition and behavior are tightly linked to synaptic function. A growing body of evidence suggests that aberrant neurotransmission, caused by changes in synaptic protein expression levels, may be a major cause underlying different brain disorders. These changes in expression result in abnormal synaptic organization or function, leading to impaired neurotransmission and unbalanced circuit operations. Here, we review the data supporting the involvement of mutations in genes coding for kainate receptor (KAR) subunits in the pathogenesis of psychiatric disorders and Down syndrome (DS). We show that most of these mutations do not affect the biophysical properties or the receptors, but rather alter subunit expression levels. On the basis of reports studying KAR genes mutations in mouse models of autism spectrum disorders and DS, we illustrate how deviations from the physiological regulatory role that these receptors play in neurotransmitter release and plasticity give rise to synaptic alterations that lead to behavioral and cognitive deficits underlying these disorders.