Scientific Understanding of Consciousness
Consciousness as an Emergent Property of Thalamocortical Activity

Dendritic Field Orientation Toward Active Axons in Developing Cortex

 

Science 29 November 2013:  Vol. 342  no. 6162  pp. 1114-1118 

BTBD3 Controls Dendrite Orientation Toward Active Axons in Mammalian Neocortex

Asuka Matsui,  May Tran, Aya C. Yoshida,  Satomi S. Kikuchi,  Mami U,  Masaharu Ogawa,  Tomomi Shimogori

RIKEN Brain Science Institute, Laboratory for Molecular Mechanisms of Thalamus Development, 2-1 Hirosawa Wako, Saitama 351-0198, Japan.

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Experience-dependent structural changes in the developing brain are fundamental for proper neural circuit formation. Here, we show that during the development of the sensory cortex, dendritic field orientation is controlled by the BTB/POZ domain–containing 3 (BTBD3). In developing mouse somatosensory cortex, endogenous Btbd3 translocated to the cell nucleus in response to neuronal activity and oriented primary dendrites toward active axons in the barrel hollow. Btbd3 also directed dendrites toward active axon terminals when ectopically expressed in mouse visual cortex or normally expressed in ferret visual cortex. BTBD3 regulation of dendrite orientation is conserved across species and cortical areas and shows how high-acuity sensory function may be achieved by the tuning of subcellular polarity to sources of high sensory activity.

Proper neural circuit development is important for the newborn animal to receive, process, and respond to information from the external sensory environment. This process critically depends on the patterning of individual neurons to shape the postsynaptic dendritic field for assembly with presynaptic axons. Dendritic remodeling is a conserved process in which postsynaptic dendrites are pruned in response to presynaptic activity during metamorphosis in Drosophila, and during the development of hippocampal CA1, cerebellar Purkinje cells, and retinal ganglion cells in mouse.

Neuronal activity from thalamocortical axons is required for morphological changes in dendrites of spiny stellate cells in the somatosensory cortex. Therefore, we examined Btbd3 expression in the NMDAR1 (N-methyl-d-aspartate receptor) cortex-specific conditional mutant mouse, where spiny stellate neurons have disoriented dendritic fields.

Based on these results, we conclude that neuronal activity triggers the translocation of BTBD3 from the cytosol to the nucleus, where it may control transcriptional programs to trim excess dendrites in developing mouse somatosensory cortex.

These results further support a role for BTBD3 in dendrite orientation toward afferents with high neuronal activity.

Dendritic refinement is known to operate by cytoskeletal modification and membrane-initiated activity-dependent pathways through molecules including neurexin-neuroligin, Wnt, and EphB-ephrinB. Here, we define a role for Btbd3 as a nuclear regulator of activity-dependent dendritic refinement. In mouse, Btbd3 is also expressed in the mouse olfactory bulb, piriform cortex, and hippocampus, where dendritic field formation of mitral cells, piriform pyramidal cells, and CA1 neurons are altered or delayed when presynaptic input is altered. This observation suggests that BTBD3 or a related family member may control dendrite remodeling in different areas of the brain. We propose that the acquisition of BTBD3 expression in a specific cortical area could provide the ability to streamline the flow of sensory information in neuronal circuits by remodeling dendritic fields to optimally respond to sensory activity. In consequence, high-acuity sensory function may have been enabled by the evolution of BTBD3 and related BTB/POZ family members in cortical development. This idea is supported by the selective expression of BTBD3 in the visual and auditory cortex of the common marmoset, a species that relies heavily on high-acuity vocal and visual communication for survival, and in the mouse, where it is expressed in high-acuity tactile and olfactory areas but not in low-acuity visual cortex. Thus, BTBD3 expression and function may help to index the evolution of precise columnar organization in many cortical regions of the mammalian brain.

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