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Role of clustered protocadherin-γ in PV-positive neurons for the formation of cortical neuronal circuit

河村, 菜々実 大阪大学 DOI:10.18910/88177

2022.03.24

概要

In the cortex, functional neural circuits are formed by specific neural connections between many types of inhibitory and excitatory neurons. However, the molecular mechanisms for the recognition of synaptic partners have remained unclear. I focused on clustered protocadherin (cPcdh) which is a diversified membrane adhesion molecule as a candidate for the recognition molecules between neurons. cPcdh consists of 58 isoforms which are divided into three gene cluster structures (α, β, and γ) in its genome and they have homophilic adhesion properties. In the CNS, cPcdhs are expressed in most neurons. Around 15 isoforms are stochastically expressed in different combinations in each cell, which gives each cell its individuality. It has been reported that the deletion of cPcdhγ in inhibitory neurons in the telencephalic region, abnormal long-lasting neural activity had been observed by whisker stimulation in the somatosensory cortex. These results suggest that cPcdhγ in inhibitory neurons could be involved in the formation of appropriate cortical neural circuits. A variety of inhibitory neurons exist in the cerebral cortex. Among them, parvalbumin-expressing (PV+) neuron occupies 50% of the inhibitory neural population and high frequently forms reciprocal connections with pyramidal neurons. It is thought to play important roles in information processing by modulation of visual response property of pyramidal cells and generation of the cortical gamma oscillation. In this study, I investigated the influence of cPcdhγ deletion in PV+ neurons on local neural circuits that form with PV+ neurons and pyramidal neurons in the primary visual cortex of mice by whole-cell patch clamp recording in conditional cPcdhγ deletion mice in PV+ neuron (PV-Cre; cPcdhγfl/fl: KO mice). The deletion of cPcdhγ in PV+ neurons did not affect the membrane properties of PV+ neurons and pyramidal neurons. To examine the connection between PV+ neurons and pyramidal neurons, simultaneous double whole-cell recordings were performed. The connection probability between PV+ neuron and pyramidal neurons and the strength of unitary inhibitory synaptic responses were similar between control and KO mice. I examined the connection relationship between PV+ and multiple neighboring pyramidal neurons in control mice by multiple whole-cell recordings. As a result, I found two types of PV+ neurons with different connectivity with pyramidal neurons: high reciprocal connectivity to neighboring pyramidal neurons (high-reciprocity) and low-reciprocity. Surprisingly, those classifications were lost in KO mice, indicating that cPcdhγ might determine the differential connectivity of each PV+ neuron within layer 2/3. To reveal the influence of cPcdhγ KO in interlaminar connectivity, I performed excitatory input map through layer 2/3 to layer 6 by whole- cell recording and laser-scan photostimulation using caged glutamate. I found that cPcdhγ-deleted PV+ neurons receive more inputs from layer 5 and layer 6 pyramidal cells compared to control mice. These results indicate that cPcdhγ is involved in not only intralaminar connections but also interlaminar connections in the visual cortex. To investigate the relationship between expression patterns of cPcdhγ isoforms in each neuron and neural connectivity, I combined whole-cell patch clamp with single cell RNA sequence. I found that reciprocally connected PV+ neurons and pyramidal neurons shared the same type of cPcdhγ isoforms significantly more compared to shuffled data. This study revealed that cPcdhγ PV+ neurons regulate the specificity of cortical intralaminar and interlaminar networks.

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参考文献

Adachi, H. The role of clustered protocadherin gamma in somatostatin-positive inhibitory neurons in the mouse barrel cortex during early stage of postnatal development. In preparation.

Ariga, R. Gamma-Protocadherins regulate cortical interneuron function. In preparation.

Atallah, B. V., Bruns, W., Carandini, M., & Scanziani, M. (2012). Parvalbumin-expressing interneurons linearly transform cortical responses to visual stimuli. Neuron, 73(1), 159-170.

Briggs, F. (2010). Organizing principles of cortical layer 6. Frontiers in neural circuits, 4, 3.

Burkhalter, A. H. (2008). Many specialists for suppressing cortical excitation. Frontiers in neuroscience, 2, 26.

Carriere, C. H., Wang, W. X., Sing, A. D., Fekete, A., Jones, B. E., Yee, Y., ... & Lefebvre, J. L. (2020). The γ-Protocadherins regulate the survival of GABAergic interneurons during developmental cell death. Journal of Neuroscience, 40(45), 8652-8668.

Celio, M. R. (1986). Parvalbumin in most γ-aminobutyric acid-containing neurons of the rat cerebral cortex. Science, 231(4741), 995-997.

DeFelipe, J. (1997). Types of neurons, synaptic connections and chemical characteristics of cells immunoreactive for calbindin-D28K, parvalbumin and calretinin in the neocortex. Journal of chemical neuroanatomy, 14(1), 1-19.

Defelipe, J., González‐Albo, M. C., Del Río, M. R., & Elston, G. N. (1999). Distribution and patterns of connectivity of interneurons containing calbindin, calretinin, and parvalbumin in visual areas of the occipital and temporal lobes of the macaque monkey. Journal of Comparative Neurology, 412(3), 515-526.

D’Souza, R. D., Bista, P., Meier, A. M., Ji, W., & Burkhalter, A. (2019). Spatial clustering of inhibition in mouse primary visual cortex. Neuron, 104(3), 588-600.

Esumi, S., Kakazu, N., Taguchi, Y., Hirayama, T., Sasaki, A., Hirabayashi, T., ... & Yagi, T. (2005). Monoallelic yet combinatorial expression of variable exons of the protocadherin-α gene cluster in single neurons. Nature genetics, 37(2), 171-176.

Gonchar, Y., & Burkhalter, A. (1997). Three distinct families of GABAergic neurons in rat visual cortex. Cerebral cortex (New York, NY: 1991), 7(4), 347-358.

Gouwens, N. W., Sorensen, S. A., Berg, J., Lee, C., Jarsky, T., Ting, J., ... & Koch, C. (2019). Classification of electrophysiological and morphological neuron types in the mouse visual cortex. Nature neuroscience, 22(7), 1182-1195.

Haas, I. G., Frank, M., Véron, N., & Kemler, R. (2005). Presenilin-dependent processing and nuclear function of γ-protocadherins. Journal of Biological Chemistry, 280(10), 9313-9319.

Hayashi, T., Ozaki, H., Sasagawa, Y., Umeda, M., Danno, H., & Nikaido, I. (2018). Single-cell full- length total RNA sequencing uncovers dynamics of recursive splicing and enhancer RNAs. Nature communications, 9(1), 1-16.

Hofer, S. B., Ko, H., Pichler, B., Vogelstein, J., Ros, H., Zeng, H., ... & Mrsic-Flogel, T. D. (2011). Differential connectivity and response dynamics of excitatory and inhibitory neurons in visual cortex. Nature neuroscience, 14(8), 1045-1052.

Ishikawa, A. W., Komatsu, Y., & Yoshimura, Y. (2014). Experience-dependent emergence of fine- scale networks in visual cortex. Journal of Neuroscience, 34(37), 12576-12586.

Kaneko, R., Kato, H., Kawamura, Y., Esumi, S., Hirayama, T., Hirabayashi, T., & Yagi, T. (2006). Allelic gene regulation of Pcdh-α and Pcdh-γ clusters involving both monoallelic and biallelic expression in single Purkinje cells. Journal of Biological Chemistry, 281(41), 30551-30560.

Kawaguchi, Y., & Kubota, Y. (1997). GABAergic cell subtypes and their synaptic connections in rat frontal cortex. Cerebral cortex (New York, NY: 1991), 7(6), 476-486.

Kisvárday, Z. F., & Eysel, U. T. (1993). Functional and structural topography of horizontal inhibitory connections in cat visual cortex. European Journal of Neuroscience, 5(12), 1558-1572.

Ko, H., Cossell, L., Baragli, C., Antolik, J., Clopath, C., Hofer, S. B., & Mrsic-Flogel, T. D. (2013). The emergence of functional microcircuits in visual cortex. Nature, 496(7443), 96-100.

Kohmura, N., Senzaki, K., Hamada, S., Kai, N., Yasuda, R., Watanabe, M., ... & Yagi, T. (1998). Diversity revealed by a novel family of cadherins expressed in neurons at a synaptic complex. Neuron, 20(6), 1137-1151.

Kubota, Y., Karube, F., Nomura, M., & Kawaguchi, Y. (2016). The diversity of cortical inhibitory synapses. Frontiers in neural circuits, 10, 27.

Leon, W. R. M., Spatazza, J., Rakela, B., Chatterjee, A., Pande, V., Maniatis, T., ... & Alvarez- Buylla, A. (2020). Clustered gamma-protocadherins regulate cortical interneuron programmed cell death. Elife, 9, e55374.

Markram, H., Toledo-Rodriguez, M., Wang, Y., Gupta, A., Silberberg, G., & Wu, C. (2004). Interneurons of the neocortical inhibitory system. Nature reviews neuroscience, 5(10), 793-807.

Masuda, H. Patch-RamDA-seq reveals the single-cell gene expression patterns of clustered protocadherins and their relationship with the neural connections and cell lineage. In preparation.

McColgan, P., Joubert, J., Tabrizi, S. J., & Rees, G. (2020). The human motor cortex microcircuit: insights for neurodegenerative disease. Nature Reviews Neuroscience, 21(8), 401-415.

Molumby, M. J., Anderson, R. M., Newbold, D. J., Koblesky, N. K., Garrett, A. M., Schreiner, D., ... & Weiner, J. A. (2017). γ-protocadherins interact with neuroligin-1 and negatively regulate dendritic spine morphogenesis. Cell reports, 18(11), 2702-2714.

Peng, Y., Barreda Tomas, F. J., Pfeiffer, P., Drangmeister, M., Schreiber, S., Vida, I., & Geiger, J. R. (2021). Spatially structured inhibition defined by polarized parvalbumin interneuron axons promotes head direction tuning. Science Advances, 7(25), eabg4693.

Reiss, K., Maretzky, T., Haas, I. G., Schulte, M., Ludwig, A., Frank, M., & Saftig, P. (2006). Regulated ADAM10-dependent ectodomain shedding of γ-protocadherin C3 modulates cell-cell adhesion. Journal of Biological Chemistry, 281(31), 21735-21744.

Runyan, C. A., & Sur, M. (2013). Response selectivity is correlated to dendritic structure in parvalbumin-expressing inhibitory neurons in visual cortex. Journal of Neuroscience, 33(28), 11724-11733.

Schreiner, D., & Weiner, J. A. (2010). Combinatorial homophilic interaction between γ- protocadherin multimers greatly expands the molecular diversity of cell adhesion. Proceedings of the National Academy of Sciences, 107(33), 14893-14898.

Shipp, S. (2007). Structure and function of the cerebral cortex. Current Biology, 17(12), R443- R449.

Southwell, D. G., Paredes, M. F., Galvao, R. P., Jones, D. L., Froemke, R. C., Sebe, J. Y., ... & Alvarez-Buylla, A. (2012). Intrinsically determined cell death of developing cortical interneurons. Nature, 491(7422), 109-113.

Steffen, D. M., Ferri, S. L., Marcucci, C. G., Blocklinger, K. L., Molumby, M. J., Abel, T., & Weiner, J. A. (2021). The γ-protocadherins interact physically and functionally with neuroligin-2 to negatively regulate inhibitory synapse density and are required for normal social interaction. Molecular neurobiology, 58(6), 2574-2589.

Südhof, T. C. (2008). Neuroligins and neurexins link synaptic function to cognitive disease. Nature, 455(7215), 903-911.

Tasic, B., Nabholz, C. E., Baldwin, K. K., Kim, Y., Rueckert, E. H., Ribich, S. A., ... & Maniatis, T. (2002). Promoter choice determines splice site selection in protocadherin α and γ pre-mRNA splicing. Molecular cell, 10(1), 21-33.

Tarusawa, E., Sanbo, M., Okayama, A., Miyashita, T., Kitsukawa, T., Hirayama, T., ... & Yoshimura,Y. (2016). Establishment of high reciprocal connectivity between clonal cortical neurons is regulated by the Dnmt3b DNA methyltransferase and clustered protocadherins. BMC biology, 14(1), 1-19.

Thu, C. A., Chen, W. V., Rubinstein, R., Chevee, M., Wolcott, H. N., Felsovalyi, K. O., ... & Maniatis, T. (2014). Single-cell identity generated by combinatorial homophilic interactions between α, β, and γ protocadherins. Cell, 158(5), 1045-1059.

Wang, X., Su, H., & Bradley, A. (2002). Molecular mechanisms governing Pcdh-γ gene expression: Evidence for a multiple promoter and cis-alternative splicing model. Genes & development, 16(15), 1890-1905.

Wonders, C. P., & Anderson, S. A. (2006). The origin and specification of cortical interneurons.Nature Reviews Neuroscience, 7(9), 687-696.

Wong, F. K., Bercsenyi, K., Sreenivasan, V., Portalés, A., Fernández-Otero, M., & Marín, O. (2018). Pyramidal cell regulation of interneuron survival sculpts cortical networks. Nature, 557(7707), 668- 673.

Wu, Q., & Maniatis, T. (1999). A striking organization of a large family of human neural cadherin- like cell adhesion genes. Cell, 97(6), 779-790.

Wu, Q., Zhang, T., Cheng, J. F., Kim, Y., Grimwood, J., Schmutz, J., ... & Maniatis, T. (2001). Comparative DNA sequence analysis of mouse and human protocadherin gene clusters. Genome research, 11(3), 389-404.

Yagi, T., & Takeichi, M. (2000). Cadherin superfamily genes: functions, genomic organization, and neurologic diversity. Genes & development, 14(10), 1169-1180.

Yizhar, O., Fenno, L. E., Prigge, M., Schneider, F., Davidson, T. J., O’shea, D. J., ... & Deisseroth,K. (2011). Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature, 477(7363), 171-178.

Yoshimura, Y., & Callaway, E. M. (2005). Fine-scale specificity of cortical networks depends on inhibitory cell type and connectivity. Nature neuroscience, 8(11), 1552-1559.

Yu, Y. C., Bultje, R. S., Wang, X., & Shi, S. H. (2009). Specific synapses develop preferentially among sister excitatory neurons in the neocortex. Nature, 458(7237), 501-504.

Yu, Y. C., He, S., Chen, S., Fu, Y., Brown, K. N., Yao, X. H., ... & Shi, S. H. (2012). Preferential electrical coupling regulates neocortical lineage-dependent microcircuit assembly. Nature, 486(7401), 113-117.

Znamenskiy, P., Kim, M. H., Muir, D. R., Iacaruso, M. F., Hofer, S. B., & Mrsic-Flogel, T. D. (2018). Functional selectivity and specific connectivity of inhibitory neurons in primary visual cortex. Biorxiv, 294835.

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