KAINATE-TYPE OF GLUTAMATE RECEPTORS REGULATE WIRING OF INTRINSIC GLUTAMATERGIC CONNECTIVITY IN THE AMYGDALA

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Perturbed information processing in the amygdala has been implicated in developmental neuropsychiatric disorders. However, little is known on the mechanisms that guide formation and refinement of intrinsic connections between amygdaloid nuclei in neonatal brain. We examined the developmental pattern of glutamatergic connection from basolateral to central amygdala (BLA-CeA) in rodents. The electrophysiology and post-hoc confocal microscopy revealed that it develops rapidly during the first ten postnatal days, before external inputs underlying amygdala dependent behaviors emerge. Kainate-type glutamate receptors are suggested to be involved in pathological mechanisms of autism spectrum disorder, Down's syndrome, bipolar disorder and schizophrenia. FISH and qPCR demonstrated high expression levels of kainate-type of ionotropic glutamate receptors in BLA during the restricted period of intensive synaptic development. Electrophysiological experiments demonstrated that tonically active KARs regulate glutamate release in neonatal amygdala via a non-canonical G-protein dependent mechanism. Genetic manipulation of the endogenous KAR activity by conditional knock-out in newborn BLA and knock-down or overexpression in the LA in vivo perturbed development of glutamatergic input to CeA. The KAR activity affects BLA-CeA connectivity by specifically regulating synaptic maturation and morphology of GABAergic neurons in CeA. Altogether data demonstrate KARs to be involved in physiological mechanism regulating developmental wiring and maturation of the intrinsic glutamatergic circuitry in the amygdala.