The Role Of Calretinin In The Development Of Sensory Cortex

The cerebral cortex is served as the top center of the nervous system and involved in regulating various activities, and the accurate perception of information is the prerequisite to for its role. The abnormity of the structures and functions of sensory cortex have been found in a plenty of developmental defect diseases such as Autism, attention deficit syndrome, Rett syndrome, etc, but the mechanism is not yet clear. Rodents live a cave life and have evolved a set of nerve systems——beard-sensory cortex pathway by which the rodents could use its tactile sense to perceive the environment information in the dark surroundings. The somatosensory cortex is consisted of typical six layers which is engaged in information receiving, information resources integrating and the beard movement coordinating and determines the function of the beard-sensory cortex pathway. All these made the rodents sensory cortex an ideal model for the study of cortical development and plasticity.The cerebral cortex receives thalamus signals mainly by the lemniscal and paralemniscal pathways and its function is accomplished by the barrel circuit and the septa circuit. The paralemniscal pathway is served as the main signal input of the barrel circuit and the septa circuit, its main target? —the L5a pyramidal neuron of sensory cortex which is involved in the formation of barrel circuit and the septa circuit simultaneously, is the key portion of the information integration and output of the sensory cortex. Hence, the normal development and maturation of the paralemniscal pathway and L5a neurons is critical to the perception and acclimatization of mice. Therefore, it is important to investigate the regulation mechanism of the development of the paralemniscal pathway and L5a neurons and understand its role in the fundamental function of the cerebral cortex.The essential period of the somatosensory cortex activity-dependent development is from PO to P15, during the period, the neurons activity that depend on the Ca+ signal pathway plays an important role. Our previous study found that:Ca+ binding protein calretinin (CR) was specifically expressed in the paralemniscal pathway relay nucleus and target section. The expression in L5a pyramidal neurons of the barrel cortex was very rare, and the expression level of CR gradually increased until it peaked at P8, then the expression level of CR gradually decreased at P15 and barely detectable at P30. CR+L5a neurons form a unique serrated pattern similar to the distributions of their presynaptic POm axon terminals; the dendrites extended to septa and display a complementary distribution pattern with barrels. Infraorbital nerve transection disrupts this unique alignment. The serrated alignment of L5a neurons is disrupted in CR mutants, indicating that CR is important for the formation of the distinct serrated arrangement of L5a pyramidal neurons. So we analysis the CR CKO mouse to detect role of CR in both the development of L5a pyramidal neurons and the function of somatosensory cortex.We first analyzed the effect of CR deleted on the development of L5a pyramidal neurons of sensory cortex. Compared with the control mouse, we, found the dendrites of L5a pyramidal neurons were shorten, and the branches complexity of the dendrites was decreased. Secondly, we observed the change of the barrel and septa in CR mutant sensory cortex, in coronal section, the configuration of barrels in L4 was disorder, some were depauperate. More neurons were abnormal accumulated in the barrel wall. In tangential section, the structure of vGLUT2+ barrels was shrink, and the septa was expansive. All those indicating that CR could regulate the development of L5a pyramidal neurons and somatosensory cortex barrel and septa formation and definement.Then, we detect the expression of molecules that may be interacted with CR. Compared with wild type mice, in the sensory cortex of CR-/- mice, the amount of the proteins Cav2.1 and Cav1.3 which are distributed in the presynaptic and postsynaptic voltage-gated calcium-ion channel were reduced; Calcium dependent AC1/cAMP signaling pathway related factor PKA and Wnt signaling pathway related factor ?-catenin were decreased as well.These results suggested that CR may affect the development of activity dependent L5a neurons and sensory cortex by regulating the expression of calcium-ion channel proteins and the activity of calcium dependent signaling pathways. ?-catenin decrease suggested that Wnt signal pathway may be involved in the postnatal development of sensory cortex. These result help us to understand the role of CR in the development of L5a neurons and sensory cortex. But the definite mechanism is under exploration in the future.