Regulation of Synapse Development byVgatDeletion from ErbB4-Positive Interneurons
| Autor: | Hongsheng Wang, Thiri W. Lin, Arnab Barik, Zhibing Tan, Lin Mei, Wen Cheng Xiong, Dong Min Yin, Egil Brudvik |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Receptor ErbB-4 genetic structures Cell Survival Vesicular Inhibitory Amino Acid Transport Proteins Neurotransmission Inhibitory postsynaptic potential Synapse Mice 03 medical and health sciences 0302 clinical medicine Interneurons Animals Research Articles Cerebral Cortex Mice Knockout Neuronal Plasticity biology Chemistry Pyramidal Cells musculoskeletal neural and ocular physiology General Neuroscience Perineuronal net Estrogen Antagonists Electroencephalography Axon initial segment Axons Extracellular Matrix Tamoxifen 030104 developmental biology nervous system Synapses biology.protein Excitatory postsynaptic potential Female Neural development Neuroscience 030217 neurology & neurosurgery Parvalbumin |
| Zdroj: | The Journal of Neuroscience. 38:2533-2550 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | GABA signaling has been implicated in neural development; however,in vivogenetic evidence is missing because mutant mice lacking GABA activity die prematurely. Here, we studied synapse development by ablating vesicular GABA transporter (Vgat) in ErbB4+interneurons. We show that inhibitory axo–somatic synapses onto pyramidal neurons vary from one cortical layer to another; however, inhibitory synapses on axon initial segments (AISs) were similar across layers. Conversely, parvalbumin-positive (PV+)/ErbB4+interneurons and PV-only interneurons receive a higher number of inhibitory synapses from PV+ErbB4+interneurons compared with ErbB4-only interneurons.Vgatdeletion from ErbB4+interneurons reduced axo–somatic or axo–axonic synapses from PV+ErbB4+interneurons onto excitatory neurons. This effect was associated with corresponding changes in neurotransmission. However, theVgatmutation seemed to have little effect on inhibitory synapses onto PV+and/or ErbB4+interneurons. Interestingly, perineuronal nets, extracellular matrix structures implicated in maturation, survival, protection, and plasticity of PV+interneurons, were increased in the cortex of ErbB4-Vgat−/−mice. No apparent difference was observed between males and females. These results demonstrate thatVgatof ErbB4+interneurons is essential for the development of inhibitory synapses onto excitatory neurons and suggest a role of GABA in circuit assembly.SIGNIFICANCE STATEMENTGABA has been implicated in neural development, butin vivogenetic evidence is missing because mutant mice lacking GABA die prematurely. Here, we ablatedVgatin ErbB4+interneurons in an inducible manner. We provide evidence that the formation of inhibitory and excitatory synapses onto excitatory neurons requiresVgatin interneurons. In particular, inhibitory axo–somatic and axo–axonic synapses are more vulnerable. Our results suggest a role of GABA in circuit assembly. |
| Databáze: | OpenAIRE |
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