大腦皮質在發育過程中會經歷複雜的層化現象。在發育早期，大腦皮質區域最先會形成一層由最初期生成的神經細胞所構成的構造，稱為preplate。隨後，快速增生的神經細胞則在preplate中間形成一層稱為cortical plate (CP) 的細胞結構，而將preplate分成外層的marginal zone (MZ) 與內層的subplate (SP) 區域。在發育的過程中，這些區域內的神經細胞彼此之間會產生對於生長發育相關的影響。隨著出生後大腦發育的成熟，最後外層的marginal zone與cortical plate會形成一個具有六層結構的大腦皮質構造，而subplate則隨之消失。在本論文中，利用kainate刺激之鈷染色法在出生前後時期 (perinatal stage) 標定大腦皮質區域表現calcium-permeable AMPA/kainate (Ca-A/K) 受器的細胞，並針對CP與SP區域觀察這類細胞的型態與分布變化。我們發現隨著這段時期的發育，位於CP內表現Ca-A/K受器的細胞會逐漸集中在較上層區域，而SP內表現此類受器的細胞則會在出生後逐漸消失減少。

[1] A. Aguiló, T.H. Schwartz, V.S. Kumar, Z.A. Peterlin, A. Tsiola, E. Soriano, R. Yuste. Involvement of cajal-retzius neurons in spontaneous correlated activity of embryonic and postnatal layer 1 from wild-type and reeler mice. J. Neurosci. 19 (1999) 10856- 10868.
[2] S. Allcorn, M. Catsicas, P. Mobbs. Developmental expression and self-regulation of Ca2+ entry via AMPA/KA receptors in the embryonic chick retina. Eur. J. Neurosci. 8 (1996) 2499-2510.
[3] K.L. Allendoerfer, C.J. Shatz. The subplate, a transient neocortical structure: its role in the development of connections between thalamus and cortex. Annu. Rev. Neurosci. 17 (1994) 185-218.
[4] S.A. Anderson, O. Marin, C. Horn, K. Jennings, J.L. Rubenstein. Distinct cortical migrations from the medial and lateral ganglionic eminences. Development 128 (2001) 353-363.
[5] C. Auladell, P. Perez-Sust, H. Supèr, E. Soriano. The early development of thalamocortical and corticothalamic projections in the mouse. Anat. Embryol. (Berl) 201 (2000) 169-179.
[6] P.V. Belichenko, D.M. Vogt Weisenhorn, J. Myklossy, M.R. Celio. Calretinin-positive Cajal-Retzius cells persist in the adult human neocortex. Neuroreport 6 (1995) 1869-1874.
[7] M. Berry, A.W. Rogers. The migration of neuroblasts in the developing cerebral cortex. J. Anat. 99 (1965) 691-709.
[8] J. Boulter, M. Hollmann, A. O'Shea-Greenfield, M. Hartley, E. Deneris, C. Maron, S. Heinemann. Molecular cloning and functional expression of glutamate receptor subunit genes. Science 249 (1990) 1033-1037.
[9] A.M. Ciabarra, J.M. Sullivan, L.G. Gahn, G. Pecht, S. Heinemann, K.A. Sevarino. Cloning and characterization of chi-1: a developmentally regulated member of a novel class of the ionotropic glutamate receptor family. J. Neurosci 15 (1995) 6498-6508.
[10] J.A. Del Río, B. Heimrich, H. Supèr, V. Borrell, M. Frotscher, E. Soriano. Differential survival of Cajal-Retzius cells in organotypic cultures of hippocampus and neocortex. J. Neurosci. 16 (1996) 6896-6907.
[11] P. Derer, M. Derer. Cajal-Retzius cell ontogenesis and death in mouse brain visualized with horseradish peroxidase and electron microscopy. Neuroscience 36 (1990) 839-856.
[12] M.J. Drian, M. Bardoul, N. König. Blockade of AMPA/kainate receptors can either decrease or increase the survival of cultured neocortical cells depending on the stage of maturation. Neurochem. Int. 38 (2001) 509-517.
[13] J. Estabel, N. König, J.M. Exbrayat. AMPA/kainate receptors permeable to divalent cations in amphibian central nervous system. Life Sci. 64 (1999) 607-616.
[14] A. Fairen, A. Cobas, M. Fonseca. Times of generation of glutamic acid decarboxylase immunoreactive neurons in mouse somatosensory cortex. J. Comp. Neurol. 251 (1986) 67-83.
[15] R. Gardette, A. Faivre-Bauman, C. Loudes, C. Kordon, J. Epelbaum. Modulation by somatostatin of glutamate sensitivity during development of mouse hypothalamic neurons in vitro. Brain Res. Dev. Brain Res. 86 (1995) 123-133.
[16] J.R. Geiger, T. Melcher, D.S. Koh, B. Sakmann, P.H. Seeburg, P. Jonas, H. Monyer. Relative abundance of subunit mRNAs determines gating and Ca2+ permeability of AMPA receptors in principal neurons and interneurons in rat CNS. Neuron 15 (1995) 193-204.
[17] A. Ghosh, C.J. Shatz. Involvement of subplate neurons in the formation of ocular dominance columns. Science 255 (1992) 1441-1443.
[18] A. Ghosh, C.J. Shatz. Segregation of geniculocortical afferents during the critical period: a role for subplate neurons. J. Neurosci. 14 (1994) 3862-3880.
[19] T. Götz, U. Kraushaar, J. Geiger, J. Lubke, T. Berger, P. Jonas. Functional properties of AMPA and NMDA receptors expressed in identified types of basal ganglia neurons. J. Neurosci. 17 (1997) 204-215.
[20] I.L. Hanganu, W. Kilb, H.J. Luhmann. Functional synaptic projections onto subplate neurons in neonatal rat somatosensory cortex. J. Neurosci. 22 (2002) 7165-7176.
[21] E. Herlenius, H. Lagercrantz. Development of neurotransmitter systems during critical periods. Exp. Neurol. 190 Suppl. 1 (2004) S8-21.
[22] M. Hollmann, M. Hartley, S. Heinemann. Ca2+ permeability of KA-AMPA--gated glutamate receptor channels depends on subunit composition. Science 252 (1991) 851-853.
[23] M. Hollmann, S. Heinemann. Cloned glutamate receptors. Annu. Rev. Neurosci. 17 (1994) 31-108.
[24] M. Hollmann, A. O'Shea-Greenfield, S.W. Rogers, S. Heinemann. Cloning by functional expression of a member of the glutamate receptor family. Nature 342 (1989) 643-648.
[25] M. Iino, S. Ozawa, K. Tsuzuki. Permeation of calcium through excitatory amino acid receptor channels in cultured rat hippocampal neurones. J. Physiol. 424 (1990) 151-165.
[26] K. Imamoto, N. Karasawa, G. Isomura, I. Nagatsu. Cajal-Retzius neurons identified by GABA immunohistochemistry in layer I of the rat cerebral cortex. Neurosci. Res. 20 (1994) 101-105.
[27] M. Johnson, R.H. Perry, M.A. Piggott, J.A. Court, D. Spurden, S. Lloyd, P.G. Ince, E.K. Perry. Glutamate receptor binding in the human hippocampus and adjacent cortex during development and aging. Neurobiol. Aging 17 (1996) 639-651.
[28] P. Jonas, C. Racca, B. Sakmann, P.H. Seeburg, H. Monyer, Differences in Ca2+ permeability of AMPA-type glutamate receptor channels in neocortical neurons caused by differential GluR-B subunit expression. Neuron 12 (1994) 1281-1289.
[29] K. Keinanen, W. Wisden, B. Sommer, P. Werner, A. Herb, T.A. Verdoorn, B. Sakmann, P.H. Seeburg. A family of AMPA-selective glutamate receptors. Science 249 (1990) 556-560.
[30] I. Kostović, P. Rakic. Cytology and time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J. Neurocytol. 9 (1980) 219-242.
[31] I. Kostović, P. Rakic. Developmental history of the transient subplate zone in the visual and somatosensory cortex of the macaque monkey and human brain. J. Comp. Neurol. 297 (1990) 441-470.
[32] A.R. Kriegstein, S.C. Noctor. Patterns of neuronal migration in the embryonic cortex. Trends Neurosci. 27 (2004) 392-399.
[33] S.S. Kumar, A. Bacci, V. Kharazia, J.R. Huguenard. A developmental switch of AMPA receptor subunits in neocortical pyramidal neurons. J. Neurosci. 22 (2002) 3005-3015.
[34] A.A. Lavdas, M. Grigoriou, V. Pachnis, J.G. Parnavelas. The medial ganglionic eminence gives rise to a population of early neurons in the developing cerebral cortex. J. Neurosci. 19 (1999) 7881-7888.
[35] S.H. Lee, M. Sheng. Development of neuron-neuron synapses. Curr. Opin. Neurobiol. 10 (2000) 125-131.
[36] H.J. Luhmann, I. Hanganu, W. Kilb. Cellular physiology of the neonatal rat cerebral cortex. Brain Res. Bull. 60 (2003) 345-353.
[37] C. Luscher, H. Xia, E.C. Beattie, R.C. Carroll, M. von Zastrow, R.C. Malenka, R.A. Nicoll. Role of AMPA receptor cycling in synaptic transmission and plasticity. Neuron 24 (1999) 649-658.
[38] M.B. Luskin, C.J. Shatz. Studies of the earliest generated cells of the cat's visual cortex: cogeneration of subplate and marginal zones. J. Neurosci. 5 (1985) 1062-1075.
[39] P. Malatesta, E. Hartfuss, M. Götz. Isolation of radial glial cells by fluorescent-activated cell sorting reveals a neuronal lineage. Development 127 (2000) 5253-5263.
[40] R.C. Malenka, R.A. Nicoll. NMDA-receptor-dependent synaptic plasticity: multiple forms and mechanisms. Trends Neurosci. 16 (1993) 521-527.
[41] J.O. Malva, A.P. Vieira, A.F. Ambrosio, C.R. Oliveira. Cobalt staining of hippocampal neurons mediated by non-desensitizing activation of AMPA but not kainate receptors. Neuroreport 14 (2003) 847-850.
[42] S.M. Maricich, E.C. Gilmore, K. Herrup. The role of tangential migration in the establishment of mammalian cortex. Neuron 31 (2001) 175-178.
[43] M. Marín-Padilla. Cajal-Retzius cells and the development of the neocortex. Trends Neurosci. 21 (1998) 64-71.
[44] M. Marin-Padílla. Dual origin of the mammalian neocortex and evolution of the cortical plate. Anat. Embryol. (Berl) 152 (1978) 109-126.
[45] R. Martín, A. Gutierrez, A. Penafiel, M. Marín-Padilla, A. de la Calle. Persistence of Cajal-Retzius cells in the adult human cerebral cortex. An immunohistochemical study. Histol. Histopathol. 14 (1999) 487-490.
[46] K. Matsuda, Y. Kamiya, S. Matsuda, M. Yuzaki. Cloning and characterization of a novel NMDA receptor subunit NR3B: a dominant subunit that reduces calcium permeability. Brain Res. Mol. Brain Res. 100 (2002) 43-52.
[47] M.P. Mattson, P. Dou, S.B. Kater. Outgrowth-regulating actions of glutamate in isolated hippocampal pyramidal neurons. J. Neurosci. 8 (1988) 2087-2100.
[48] M.P. Mattson, S.B. Kater. Calcium regulation of neurite elongation and growth cone motility. J. Neurosci. 7 (1987) 4034-4043.
[49] M.L. Mayer, G.L. Westbrook, P.B. Guthrie. Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature 309 (1984) 261-263.
[50] A.K. McAllister. Subplate neurons: a missing link among neurotrophins, activity, and ocular dominance plasticity?, Proc. Natl. Acad. Sci. USA 96 (1999) 13600-13602.
[51] C.J. McBain, R. Dingledine. Heterogeneity of synaptic glutamate receptors on CA3 stratum radiatum interneurones of rat hippocampus. J. Physiol. 462 (1993) 373-392.
[52] M.W. Miller. Cogeneration of retrogradely labeled corticocortical projection and GABA-immunoreactive local circuit neurons in cerebral cortex. Brain Res. 355 (1985) 187-192.
[53] M.C. Mione, J.F. Cavanagh, B. Harris, J.G. Parnavelas. Cell fate specification and symmetrical/asymmetrical divisions in the developing cerebral cortex. J. Neurosci. 17 (1997) 2018-2029.
[54] J.P. Misson, C.P. Austin, T. Takahashi, C.L. Cepko, V.S. Caviness, Jr.. The alignment of migrating neural cells in relation to the murine neopallial radial glial fiber system. Cereb. Cortex 1 (1991) 221-229.
[55] T. Miyata, A. Kawaguchi, H. Okano, M. Ogawa. Asymmetric inheritance of radial glial fibers by cortical neurons. Neuron 31 (2001) 727-741.
[56] Z. Molnár, C. Blakemore. How do thalamic axons find their way to the cortex?. Trends Neurosci. 18 (1995) 389-397.
[57] M. Morales, Y. Goda. Nomadic AMPA receptors and LTP. Neuron 23 (1999) 431-434.
[58] B. Nadarajah, P. Alifragis, R.O. Wong, J.G. Parnavelas. Neuronal migration in the developing cerebral cortex: observations based on real-time imaging. Cereb. Cortex 13 (2003) 607-611.
[59] B. Nadarajah, J.G. Parnavelas. Modes of neuronal migration in the developing cerebral cortex. Nat. Rev. Neurosci. 3 (2002) 423-432.
[60] I. Nagy, C.J. Woolf, A. Dray, L. Urban. Cobalt accumulation in neurons expressing ionotropic excitatory amino acid receptors in young rat spinal cord: morphology and distribution. J. Comp. Neurol. 344 (1994) 321-335.
[61] S.C. Noctor, A.C. Flint, T.A. Weissman, R.S. Dammerman, A.R. Kriegstein. Neurons derived from radial glial cells establish radial units in neocortex. Nature 409 (2001) 714-720.
[62] S.C. Noctor, A.C. Flint, T.A. Weissman, W.S. Wong, B.K. Clinton, A.R. Kriegstein. Dividing precursor cells of the embryonic cortical ventricular zone have morphological and molecular characteristics of radial glia. J. Neurosci. 22 (2002) 3161-3173.
[63] M. Ogawa, T. Miyata, K. Nakajima, K. Yagyu, M. Seike, K. Ikenaka, H. Yamamoto, K. Mikoshiba. The reeler gene-associated antigen on Cajal-Retzius neurons is a crucial molecule for laminar organization of cortical neurons. Neuron 14 (1995) 899-912.
[64] T. Okada, K. Schultz, W. Geurtz, H. Hatt, R. Weiler. AMPA-preferring receptors with high Ca2+ permeability mediate dendritic plasticity of retinal horizontal cells. Eur. J. Neurosci. 11 (1999) 1085-1095.
[65] D.D. O'Leary, B.L. Schlaggar, R. Tuttle. Specification of neocortical areas and thalamocortical connections. Annu. Rev. Neurosci. 17 (1994) 419-439.
[66] J.G. Parnavelas. The origin and migration of cortical neurones: new vistas. Trends Neurosci. 23 (2000) 126-131.
[67] A.V. Paternain, M. Morales, J. Lerma. Selective antagonism of AMPA receptors unmasks kainate receptor-mediated responses in hippocampal neurons. Neuron 14 (1995) 185-189.
[68] D.K. Patneau, M.L. Mayer. Structure-activity relationships for amino acid transmitter candidates acting at N-methyl-D-aspartate and quisqualate receptors. J. Neurosci. 10 (1990) 2385-2399.
[69] J.D. Peduzzi. Genesis of GABA-immunoreactive neurons in the ferret visual cortex. J. Neurosci. 8 (1988) 920-931.
[70] F. Polleux, K.L. Whitford, P.A. Dijkhuizen, T. Vitalis, A. Ghosh. Control of cortical interneuron migration by neurotrophins and PI3-kinase signaling. Development 129 (2002) 3147-3160.
[71] R.M. Pruss, R.L. Akeson, M.M. Racke, J.L. Wilburn. Agonist-activated cobalt uptake identifies divalent cation-permeable kainate receptors on neurons and glial cells. Neuron 7 (1991) 509-518.
[72] P. Rakic. Neurons in rhesus monkey visual cortex: systematic relation between time of origin and eventual disposition. Science 183 (1974) 425-427.
[73] P. Rakic. Principles of neural cell migration. Experientia 46 (1990) 882-891.
[74] G. Riedel, B. Platt, J. Micheau. Glutamate receptor function in learning and memory. Behav. Brain Res. 140 (2003) 1-47.
[75] R.T. Robertson, C.M. Annis, J. Baratta, S. Haraldson, J. Ingeman, G.H. Kageyama, E. Kimm, J. Yu. Do subplate neurons comprise a transient population of cells in developing neocortex of rats? J. Comp. Neurol. 426 (2000) 632-650.
[76] T.E. Salt. Glutamate receptor functions in sensory relay in the thalamus. Philos Trans R Soc. Lond. B. Biol. Sci. 357 (2002) 1759-1766.
[77] H.B. Sarnat, L. Flores-Sarnat. Cajal-Retzius and subplate neurons: their role in cortical development. Eur. J. Paediatr Neurol. 6 (2002) 91-97.
[78] M. Schwartz, M. Rochas, B. Weller, A. Sheinkman, I. Tal, D. Golan, N. Toubi, I. Eldar, B. Sharf, D. Attias. High association of anticardiolipin antibodies with psychosis. J. Clin. Psychiatry 59 (1998) 20-23.
[79] C.J. Shatz, M.B. Luskin. The relationship between the geniculocortical afferents and their cortical target cells during development of the cat's primary visual cortex. J Neurosci 6 (1986) 3655-3668.
[80] S. Skradski, H.S. White. Topiramate blocks kainate-evoked cobalt influx into cultured neurons. Epilepsia 41 Suppl 1 (2000) S45-47.
[81] T. Soda, R. Nakashima, D. Watanabe, K. Nakajima, I. Pastan, S. Nakanishi. Segregation and coactivation of developing neocortical layer 1 neurons. J. Neurosci. 23 (2003) 6272-6279.
[82] E. Soriano, R.M. Alvarado-Mallart, N. Dumesnil, J.A. Del Río, C. Sotelo. Cajal-Retzius cells regulate the radial glia phenotype in the adult and developing cerebellum and alter granule cell migration. Neuron 18 (1997) 563-577.
[83] H. Supèr, E. Soriano, H.B. Uylings. The functions of the preplate in development and evolution of the neocortex and hippocampus. Brain Res. Brain Res. Rev. 27 (1998) 40-64.
[84] N. Tamamaki, K. Nakamura, K. Okamoto, T. Kaneko. Radial glia is a progenitor of neocortical neurons in the developing cerebral cortex. Neurosci. Res. 41 (2001) 51-60.
[85] C.S. Toomim, W.R. Millington. Regional and laminar specificity of kainate-stimulated cobalt uptake in the rat hippocampal formation. J. Comp. Neurol. 402 (1998) 141-154.
[86] D.M. Turetsky, L.M. Canzoniero, S.L. Sensi, J.H. Weiss, M.P. Goldberg, D.W. Choi. Cortical neurones exhibiting kainate-activated Co2+ uptake are selectively vulnerable to AMPA/kainate receptor-mediated toxicity. Neurobiol. Dis. 1 (1994) 101-110.
[87] G.G. Turrigiano. AMPA receptors unbound: membrane cycling and synaptic plasticity. Neuron 26 (2000) 5-8.
[88] F. Valverde, J.A. De Carlos, L. Lopez-Mascaraque. Time of origin and early fate of preplate cells in the cerebral cortex of the rat. Cereb. Cortex 5 (1995) 483-493.
[89] T.A. Verdoorn, N. Burnashev, H. Monyer, P.H. Seeburg, B. Sakmann. Structural determinants of ion flow through recombinant glutamate receptor channels. Science 252 (1991) 1715-1718.
[90] H. Wichterle, J.M. Garcia-Verdugo, D.G. Herrera, A. Alvarez-Buylla. Young neurons from medial ganglionic eminence disperse in adult and embryonic brain. Nat. Neurosci. 2 (1999) 461-466.
[91] H. Wichterle, D.H. Turnbull, S. Nery, G. Fishell, A. Alvarez-Buylla. In utero fate mapping reveals distinct migratory pathways and fates of neurons born in the mammalian basal forebrain. Development 128 (2001) 3759-3771.
[92] L.R. Williams, J.F. Pregenzer, J.A. Oostveen. Induction of cobalt accumulation by excitatory amino acids within neurons of the hippocampal slice. Brain Res. 581 (1992) 181-189.
[93] S.P. Wise, E.G. Jones. Developmental studies of thalamocortical and commissural connections in the rat somatic sensory cortex. J. Comp. Neurol. 178 (1978) 187-208.
[94] H. Yin, D. Turetsky, D.W. Choi, J.H. Weiss. Cortical neurones with Ca2+ permeable AMPA/kainate channels display distinct receptor immunoreactivity and are GABAergic. Neurobiol. Dis. 1 (1994) 43-49.
[95] H.Z. Yin, A.D. Lindsay, J.H. Weiss. Kainate injury to cultured basal forebrain cholinergic neurons is Ca2+ dependent. Neuroreport 5 (1994) 1477-1480.
[96] Y.H. Yoon, K.H. Jeong, M.J. Shim, J.Y. Koh. High vulnerability of GABA-immunoreactive neurons to kainate in rat retinal cultures: correlation with the kainate-stimulated cobalt uptake. Brain Res. 823 (1999) 33-41.
[97] N. Zecevic, A. Milosevic. Initial development of gamma-aminobutyric acid immunoreactivity in the human cerebral cortex. J. Comp. Neurol. 380 (1997) 495-506.
[98] 方怡之(2002) 胎鼠大腦神經元麩胺酸受器對鈣離子通透性之研究. 國立清華大學碩士論文
.