Maturation Of Thalamocortical Synapses In The Somatosensory Cortex Depends On Neocortical AKAP5 Expression

Sensory cortex topographic maps consist of organized arrays of thalamocortical afferents（TCAs）that project into distinct areas of the cortex.Formation of topographic maps in sensory cortices is a prerequisite for functional maturation of the neocortex.Studies have shown that the formation of topographic maps and the maturation of thalamocortical synapses in the somatosensory cortex depend on the cyclic adenosine 5′-monophosphate-（c AMP）-protein kinase A（PKA）signaling pathway.AKAP5 is a scaffold protein（also called AKAP79 in humans or AKAP150 in rodents;AKAP79/150）that serves as a signaling hub that links c AMP and PKA signaling.Objective: our study here aims to 1.Study the formation of topographic maps in the somatosensory cortex in the absence of the AKAP5 gene 2.Investigate maturation of thalamocortical synapses in somatosensory cortex of AKAP5 gene knockout mice during postnatal development 3.Examine morphological development of cortical layer 4 neurons in mice lacking AKAP5 gene Method: 1.Generation of AKAP5 gene neocortex-specific knock out mice,and Western Blot and droplet digital PCR techniques were used to examine their protein and m RNA expressions 2.Study the development of cortical topographic maps of AKAP5 gene-specific deletion mice and normal mice with cytochrome oxidase staining experiments 3.The cortex of mice at 7 and 15 days after birth was dissected,and the development of cortical topographic maps of AKAP5 gene-specific deletion mice and normal mice was observed by Nissl staining experiments.4.Neocortex was isolated and stored in artificial cerebrospinal fluid after 95% O₂ and 5% CO₂ equilibration,then using in vitro electrophysiology techniques to detect the number of silent synapses in the cortex of AKAP5-specific deletion mice and normal mice to estimate cortical synapse development 5.Using fluorescence imaging and neuronal cell reconstruction to compare the morphological differences between cortical neurons in AKAP5-specific deletion mice and normal mice Results: Comprehensive analysis of the above results,we found that Cx AKAP5 KO mice displayed impaired cortical barrel maps.Electrophysiological recordings showed that the AMPA/NMDA ratio was reduced,and silent synapses were increased in thalamocortical synapses of Cx AKAP5 KO mice during postnatal development.Morphological analysis of layer IV cortical neurons demonstrated that dendritic refinement of these neurons was abnormal.These results indicate that AKAP5 is necessary for both topographic map formation and maturation of thalamocortical synapses as well as morphological development of cortical neurons in the somatosensory cortex.