KCC2 Regulates Dendritic Spine Formation in a Brain-Region Specific and BDNF Dependent Manner

• Published in: Cerebral cortex (New York, N.Y. 1991) Vol. 28; no. 11; pp. 4049 - 4062
• Main Authors: Awad, Patricia Nora, Amegandjin, Clara Akofa, Szczurkowska, Joanna, Carriço, Josianne Nuñes, Fernandes do Nascimento, Antônia Samia, Baho, Elie, Chattopadhyaya, Bidisha, Cancedda, Laura, Carmant, Lionel, Di Cristo, Graziella
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01-11-2018
• Subjects: Animals; Brain-Derived Neurotrophic Factor - metabolism; Brain-Derived Neurotrophic Factor - physiology; CA1 Region, Hippocampal - cytology; CA1 Region, Hippocampal - growth & development; Dendritic Spines - physiology; Gene Expression Regulation, Developmental; K Cl- Cotransporters; Original; Pyramidal Cells - physiology; Rats, Sprague-Dawley; Somatosensory Cortex - growth & development; Symporters - metabolism; Symporters - physiology; development; brain-derived neurotrophic factor; KCC2; dendritic spines; synapse formation
• ISSN: 1047-3211; 1460-2199
• DOI: 10.1093/cercor/bhy198

Abstract
KCC2 is the major chloride extruder in neurons. The spatiotemporal regulation of KCC2 expression orchestrates the developmental shift towards inhibitory GABAergic drive and the formation of glutamatergic synapses. Whether KCC2’s role in synapse formation is similar in different brain regions is unknown. First, we found that KCC2 subcellular localization, but not overall KCC2 expression levels, differed between cortex and hippocampus during the first postnatal week. We performed site-specific in utero electroporation of KCC2 cDNA to target either hippocampal CA1 or somatosensory cortical pyramidal neurons. We found that a premature expression of KCC2 significantly decreased spine density in CA1 neurons, while it had the opposite effect in cortical neurons. These effects were cell autonomous, because single-cell biolistic overexpression of KCC2 in hippocampal and cortical organotypic cultures also induced a reduction and an increase of dendritic spine density, respectively. In addition, we found that the effects of its premature expression on spine density were dependent on BDNF levels. Finally, we showed that the effects of KCC2 on dendritic spine were dependent on its chloride transporter function in the hippocampus, contrary to what was observed in cortex. Altogether, these results demonstrate that KCC2 regulation of dendritic spine development, and its underlying mechanisms, are brain-region specific.