Autism spectrum disorders (ASDs) are pervasive neurodevelopmental disorders that include syndromes with familial conditions. Among these, the Phelan-McDermid syndrome is associated with the co-deletion of SHANK3 and IB2 genes at the chromosome 22q terminus. Although much attention has been devoted to characterize SHANK3 mutations, very little is known about the role of IB2 in ASDs. The IB2 protein is expressed at synapses and takes part to the NMDA receptor (NMDAR) interactome in the postsynaptic densities. Experimental disruption of the IB2 gene in transgenic mice determined an enhanced NMDAR-mediated transmission at the mossy fiber-granule cell (MF-GrCs) synapse in the cerebellum. Moreover, IB2 knocked-out (IB2 KO) mice showed motor and cognitive deficits, making them a reliable ASD model [1]. Herein, we further investigated the synaptic and circuit modifications in IB2 KO mice. In particular, we addressed the potential alterations in the excitatory/inhibitory (E/I) balance and long-term potentiation (LTP) induction in the cerebellar granular layer of IB2 KO mice.
Cerebellar hyper-plasticity in the IB2 KO mouse model of autism
SODA, TERESA;MAPELLI, LISA;LOCATELLI, FRANCESCA;BOTTA, LAURA;PRESTORI, FRANCESCA;D'ANGELO, EGIDIO UGO
2017-01-01
Abstract
Autism spectrum disorders (ASDs) are pervasive neurodevelopmental disorders that include syndromes with familial conditions. Among these, the Phelan-McDermid syndrome is associated with the co-deletion of SHANK3 and IB2 genes at the chromosome 22q terminus. Although much attention has been devoted to characterize SHANK3 mutations, very little is known about the role of IB2 in ASDs. The IB2 protein is expressed at synapses and takes part to the NMDA receptor (NMDAR) interactome in the postsynaptic densities. Experimental disruption of the IB2 gene in transgenic mice determined an enhanced NMDAR-mediated transmission at the mossy fiber-granule cell (MF-GrCs) synapse in the cerebellum. Moreover, IB2 knocked-out (IB2 KO) mice showed motor and cognitive deficits, making them a reliable ASD model [1]. Herein, we further investigated the synaptic and circuit modifications in IB2 KO mice. In particular, we addressed the potential alterations in the excitatory/inhibitory (E/I) balance and long-term potentiation (LTP) induction in the cerebellar granular layer of IB2 KO mice.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
