Abstract
The flow of information between neurons in many neural circuits is controlled by a highly specialized site of cell-cell contact known as a synapse. A number of molecules have been identified that are involved in central nervous system synapse development, but knowledge is limited regarding whether these cues direct organization of specific synapse types or on particular regions of individual neurons. Glutamate is the primary excitatory neurotransmitter in the brain, and the majority of glutamatergic synapses occur on mushroom-shaped protrusions called dendritic spines. Changes in the morphology of these structures are associated with long-lasting modulation of synaptic strength thought to underlie learning and memory, and can be abnormal in neuropsychiatric disease. Here, we use rat cortical slice cultures to examine how a previously-described synaptogenic molecule, the EphB2 receptor tyrosine kinase, regulates dendritic protrusion morphology in specific regions of the dendritic arbor in cortical pyramidal neurons. We find that alterations in EphB2 signaling can bidirectionally control protrusion length, and knockdown of EphB2 expression levels reduces the number of dendritic spines and filopodia. Expression of wild-type or dominant negative EphB2 reveals that EphB2 preferentially regulates dendritic protrusion structure in basal dendrites. Our findings suggest that EphB2 may act to specify synapse formation in a particular subcellular region of cortical pyramidal neurons.
Highlights
Mature cortical neurons are decorated with thousands of dendritic spines
To examine how alterations in EphB2 signaling in individual neurons impacts dendritic protrusion formation in cortex, we transfected neurons in organotypic brain slice cultures of rat cortex with constructs expressing wild-type or dominant negative EphB2 along with green fluorescent protein (EGFP)
Manipulation of EphB2 expression and signaling induces a shift in dendritic protrusion structure between spines and filopodia [15,17], and in some preparations can result in alterations of overall dendritic protrusion density [25]
Summary
Mature cortical neurons are decorated with thousands of dendritic spines. These structures are the site of the majority of excitatory synapses and are thought to be critical for the generation and expression of synaptic plasticity [1,2]. Cortical pyramidal neurons have stereotyped morphology, with long apical dendrites that project to the cortical surface and short branched basal dendrites that remain largely within the same cortical layer as the cell soma [5,6]. Synaptic inputs onto cortical neurons appear to be spatially segregated in a subcellular manner, with projections from particular cortical layers or areas of brain synapsing on either the apical or basal portion of the dendritic arbor [7,8]. These regions of the dendritic tree have distinct functional significance with regard to integration of inputs, excitability, and plasticity [6]. Cortical pyramidal neurons have specialized morphology and channel distribution, it is not known whether different mechanisms guide the formation of synaptic structures in specific parts of the dendritic arbor
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