神經鞘網狀結構是一種包覆在細胞體及近端樹狀突的特殊細胞外基質。其發育的時序高度地與神經網絡可塑性關鍵期的結束相符。在神經網絡可塑性關鍵期間需要接受適當的外來刺激才得以塑造完整的神經網絡。長期抑制現象（Long-term depression）是一種持續性的神經突出傳導的減弱，並且被認為與學習記憶有關。有趣的是，在海馬迴CA1區域的Schaffer collateral神經突觸中，長期抑制現象的誘導隨著年齡增加而遞減。然而，此現象的作用機制仍然不清楚。因此本研究宗旨為探討神經鞘網狀結構的完整性對於小鼠海馬迴CA1區域隨年齡增長而遞減的長期抑制現象的影響。在本研究觀察到，從小鼠出生後14天到28天，於海馬迴CA1區域的長期抑制現象的逐漸減弱。同時也觀察到神經鞘網狀結構包覆在海馬迴CA1區域的parvalbumin 聯絡神經元外。利用Chondroitinase ABC （ChABC）酵素可破壞神經鞘網狀結構，並且在成年小鼠（約出生後60天）成功地利用低頻電刺激促進了長期抑制現象。此外，在小鼠發育早期給予bumetanide，可減少神經鞘網狀結構的數目並且在出生後28天的小鼠海馬迴CA1區域促進了長期抑制現象。另外，本研究也證明了，ChABC處理後於成鼠海馬迴CA1區域促進的長期抑制現象屬於N-Methyl-D-aspartic acid受體（NMDAR）所調控，而非metabotropic glutamate受體（mGluR）所調控。同時，γ-aminobutyric acid （GABA）訊息的恆定對成鼠的海馬迴CA1區域的神經網絡長期抑制現象產生了改變。而鈣離子內流的通透性在神經鞘網狀結構存在下也受到了改變，因提高細胞外鈣離子濃度後可在正常成鼠的海馬迴CA1區域造成長期抑制現象，卻無法在經過酵素破壞神經鞘網狀結構的CA1區域造成更大的長期抑制現象。再者，利用過極化活化陽離子通道的抑製劑可抑制經酵素破壞神經鞘網狀結構的CA1區域的長期抑制現象。最後本研究也發現，神經鞘網狀結構於海馬迴CA1區域的生理功能可能為Morris水迷宮實驗的學習階段扮演重要的角色。綜合以上結果，此實驗發現神經鞘網狀結構於海馬迴CA1區域的形成與長期抑制現象有著負相關性，且會抑制投射到CA1區域興奮性神經突出可塑性。

Perineuronal nets (PNNs) are unique extracellular matrix structures that enshealth the soma and proximal dendrites of neurons. The developmental maturation of PNNs has been shown to highly correlate with closure of critical period of plasticity in which appropriate experience moulds neural network organization. Long-term depression (LTD) is a persistent activity-dependent decrease in the efficacy of synaptic transmission and a prominent feature of theoretical schemes for learning and memory. Of interest, early studies on LTD at hippocampal CA1 synapses reported an apparent decline in degree of LTD with increasing age. However, the actual mechanism underlying age dependence of LTD remains unclear. The present study examines the impact of PNN integrity on age-dependent decline in the efficacy of LTD induction at Schaffer collateral CA1 synapses of mouse hippocampus. Here, we observed a dramatic decline in degree of LFS-induced LTD with increasing age from postnatal day (P) 14 to P28 at Schaffer collateral CA1 synapses. Chondroitinase ABC (ChABC) treatment resulted in the disruption of PNNs and enhanced the induction of LFS-induced LTD in adult mice (P60) at the hippocampal CA1. Early-life bumetanide administration decreased the postnatal development of PNNs and promoted the degree of LTD at P28. On the other hand, the ChABC-induced LTD was a N-Methyl-D-aspartic acid receptor (NMDAR) dependent instead of metabotropic glutamate receptor (mGluR) dependent. Whilst, we found the GABAergic signalling homeostasis has changed in the adult hippocampal CA1 network in accordance with the LTD induction rule. Furthermore, permeability of calcium ions influx was changed with PNNs, as the elevation of extracellular calcium ions induced LTD in vehicle but did not further enhanced in ChABC treated slices. In addition, blockade of hyperpolarization-activated cation channels (Ih channels) using ZD7288 can reverse the LTD expression of ChABC treated slices. Finally, the physiological importance of PNNs in CA1 was shown at the acquisition learning in the Morris water maze experiment. We provide a new insight into a previously unrecognized role for PNNs in restricting plasticity at excitatory synapses onto hippocampal CA1 neurons.

REFERENCES
1. Allen, B., Ingram, E., Takao, M., Smith, M.J., Jakes, R., Virdee, K., Yoshida, H., Holzer, M., Craxton, M., Emson, P.C., Atzori, C., Migheli, A., Crowther, R.A., Ghetti, B., Spillantini, M.G. and Goedert, M. (2002) Abundant tau filaments and nonapoptotic neurodegeneration in transgenic mice expressing human P301S tau protein. J. Neurosci. 22, 9340 –9351.
2. Akhondzadeh, S., Mohammadi, M.R. and Kashani, L. (2002). Potentiation of muscimol-induced long-term depression by benzodiazepines but not zolpidem. Prog. Neuropsychopharmacol. Biol. Psychiatry. 26, 1161-1166.
3. Artola, A., Brocher, S., and Singer, W. (1990). Different voltage-dependent thresholds for inducing long-term depression and long-term potentiation in slices of rat visual cortex. Nature 347, 69-72.
4. Balmer, T.S. (2016). Perineuronal nets enhance the excitability of fast-spiking neurons. eNeuro 3, 1-13.
5. Banerjee, S.B., Gutzeit, V.A., Baman, J., Aoued, H.S., Doshi, N.K., Liu, R.C., and Ressler, K.J. (2017). Perineuronal nets in the adult sensory cortex are necessary for fear learning. Neuron 95, 169-179 e163.
6. Ben-Ari, Y., Woodin, M.A., Sernagor, E., Cancedda, L., Vinay, L., Rivera, C., Legendre, P., Luhmann, H.J., Bordey, A., Wenner, P., et al. (2012). Refuting the challenges of the developmental shift of polarity of GABA actions: GABA more exciting than ever! Front. Cell Neurosci. 6, 35-52.
7. Bienestock, E.L., Cooper, L.N., and Munro, P.W. (1982). Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex. J. Neurosci. 2, 32-48.
8. Bikbaev, A., Frischknecht, R., and Heine, M. (2015). Brain extracellular matrix retains connectivity in neuronal networks. Sci. Rep. 5, 14527-14541.
9. Blue, M.E., and Parnavelas, J.G. (1983). The formation and maturation of synapses in the visual cortex of the rat. I. qualitative analysis. J. Neurocytol. 12, 599-616.
10. Bruckner, G., Grosche, J., Schmidt, S., Hartig, W., Margolis, R.U., Delpech, B., and Schachner, M. (2000). Postnatal development of perineuronal nets in wild-type mice and in a mutant deficient in tenascin-R. J. Comp. Neurol. 428, 616-629.
11. Bukalo, O., Schachner, M., and Dityatev, A. (2001). Modification of extracellular matrix by enzymatic removal of chondroitin sulfate. Neuroscience 104, 359-369.
12. Buzsaki, G. (1986). Hippocampal sharp waves: their origin and significance. Brain Res. 398, 242-252.
13. Buzsaki, G. (2002). Theta oscillations in the hippocampus. Nature 33, 325-340.
14. Carstens, K.E., Phillips, M.L., Pozzo-Miller, L., Weinberg, R.J., and Dudek, S.M. (2016). Perineuronal nets suppress plasticity of excitatory synapses on CA2 pyramidal neurons. J. Neurosci. 36, 6312-6320.
15. Christopher, M., Norris, D.L.K., and Thomas, C. Foster (1996). Increased susceptibility to induction of long-term depression and long-term potentiation reversal during aging. J. Neurosci. 16, 5382-5392.
16. Comper, W.D., and Preston, B.N. (1975). Model connective tissue system membrane phenomena of gel membranes containing polyelectrolytes. J. Colloid. Interface Sci. 53, 391-401.
17. Cuervo, L.A., Pita J. C., and Howell, D.S. (1973). Inhibition of calcium phosphate mineral growth by proteiglycan aggregate fractions in a synthetic lymph. Calc. Tiss. Res. 13, 1-13.
18. Cull-Candy, S., Kelly, L., and Farrant, M. (2006). Regulation of Ca2+-permeable AMPA receptors: synaptic plasticity and beyond. Curr. Opin. Neurobiol. 16, 288-297.
19. Deidda, G., Allegra, M., Cerri, C., Naskar, S., Bony, G., Zunino, G., Bozzi, Y., Caleo, M., and Cancedda, L. (2015). Early depolarizing GABA controls critical-period plasticity in the rat visual cortex. Nat. Neurosci. 18, 87-96.
20. Dingledine, R., Hynes, M.A., and King, G.L. (1986). Involment of N-methyl-D-aspartate receptors in epileptiform bursting in the rat hippocampal slice. J. Physiol. 380, 175-189.
21. Dityatev, A., Bruckner, G., Dityateva, G., Grosche, J., Kleene, R., and Schachner, M. (2007). Activity-dependent formation and functions of chondroitin sulfate-rich extracellular matrix of perineuronal nets. Dev. Neurobiol. 67, 570-588.
22. Donato, F., Chowdhury, A., Lahr, M., and Caroni, P. (2015). Early- and late-born parvalbumin basket cell subpopulations exhibiting distinct regulation and roles in learning. Neuron 85, 770-786.
23. Dong, Z., Bai, Y., Wu, X., Li, H., Gong, B., Howland, J. G., Huang, Y., He, W., Li, T. and Wang, Y. T. (2013). Hippocampal long-term depression mediates spatial reversal learning in the Morris water maze. Neuropharmacology 64, 65-73.
24. Dudek, S.M., and Bear, M.F. (1992). Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade. Proc. Natl. Acad. Sci. U.S.A 89, 4363-4367.
25. Dyck, S.M., and Karimi-Abdolrezaee, S. (2015). Chondroitin sulfate proteoglycans: Key modulators in the developing and pathologic central nervous system. Exp. Neurol. 269, 169-187.
26. Fagiolini M., and Hensch, T.K. (2000). Inhibitory threshold for critical-period activation in primary visual cortex. Nature 4, 183-186.
27. Favuzzi, E., Marques-Smith, A., Deogracias, R., Winterflood, C.M., Sanchez-Aguilera, A., Mantoan, L., Maeso, P., Fernandes, C., Ewers, H., and Rico, B. (2017). Activity-dependent gating of parvalbumin interneuron function by the perineuronal net protein brevican. Neuron 95, 639-655.
28. Frischknecht, R., Heine, M., Perrais, D., Seidenbecher, C.I., Choquet, D., and Gundelfinger, E.D. (2009). Brain extracellular matrix affects AMPA receptor lateral mobility and short-term synaptic plasticity. Nat. Neurosci. 12, 897-904.
29. Gogolla, N., Caroni, P., Lüthi, A., and Henry, C. (2018). Perineuronal nets protect fear memories from erasure. Science 325, 1258-1261.
30. Groc, L., Heine, M., Cousins, S.L., Stephenson, F.A., Lounis, B., Cognet, L., and Choquet, D. (2006). NMDA receptor surface mobility depends on NR2A-2B subunits. Proc. Natl. Acad. Sci. U.S.A 103, 18769-18774.
31. Goutman, J.D. and Calvo, D.J. (2004). Studies on the mechanisms of action of picrotoxin, quercetin and pregnanolone at the GABAρ1 receptor. Br. J. Pharmacol. 141, 717-727.
32. Guimaraes, A., Zaremba, S., and Hockfield, S. (1990). Molecular and morphological changes in the cat lateral geniculate nucleus and visual cortex induced by visual deprevation are revealed by monoclonal antibodies cat 304 and cat 301. J. Neurosci. 10, 3014-3024.
33. Gulyas, A.I., Szabo, G.G., Ulbert, I., Holderith, N., Monyer, H., Erdelyi, F., Szabo, G., Freund, T.F., and Hajos, N. (2010). Parvalbumin-containing fast-spiking basket cells generate the field potential oscillations induced by cholinergic receptor activation in the hippocampus. J. Neurosci. 30, 15134-15145.
34. Gustafsson, B., Wigstrom, H., Abraham, W.C., and Huang, Y.Y. (1987). Long-term potentiation in the hippocampus using depolarizing current pulses as the conditioning stimulus to single volley synaptic potentials. J. Neurosci. 7, 774-780.
35. Happela, M.F.K., Niekischa, H., Riveraa, L.L.C., Ohla F.W., Delianoa, M., and Frischknechtd R. (2014). Enhanced cognitive flexibility in reversal learning induced by removal of the extracellular matrix in auditory cortex. Proc. Natl. Acad. Sci. U.S.A 111, 2800-2805.
36. Harauzov, A., Spolidoro, M., DiCristo, G., De Pasquale, R., Cancedda, L., Pizzorusso, T., Viegi, A., Berardi, N., and Maffei, L. (2010). Reducing intracortical inhibition in the adult visual cortex promotes ocular dominance plasticity. J. Neurosci. 30, 361-371.
37. Hardingham, G.E., and Bading, H. (2010). Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nat. Rev. Neurosci. 11, 682-696.
38. Hartig, W., Derouiche, A., Welt, K., Brauer, K., Grosche, J., Mader, M., Reichenbach, A., and Bruckner, G. (1999). Cortical neurons immunoreactive for the postassium channel Kv3.1b subunit are predominantly surrounded by perineuronal nets presumed as buffering system for cations. Brain Res. 842, 15-29.
39. Hensch, T.K. (2005). Critical period plasticity in local cortical circuits. Nat. Rev. Neurosci. 6, 877-887.
40. Hockfield, S., Tootell, Roger B.H., and Zaremba, S. (1990). Molecular differences among neurons reveal an organization of human visual cortex. Proc. Natl. Acad. Sci. U.S.A 87, 3027-3031.
41. Hrabetová, S., Masri, D., Tao, L., Xiao, F. and Nicholson, C. (2009). Calcium diffusion enhanced after cleavage of negatively charged components of brain extracellular matrix by chondroitinase ABC. J. Physiol. 587, 4029-4049.
42. Huang, C.C. and Hsu, K.S. (2003). Reexamination of the role of hyperpolarization-activated cation channels in short- and long-term plasticity at hippocampal mossy fiber synapses. Neuropharmacology 44, 968-981.
43. Huang, C.C. and Hsu, K.S. (2005). Sustained activation of metabotropic glutamate receptor 5 and protein tyrosine phosphatases mediate the expression of (S)-3,5-dihydroxyphenylglycine-induced long-term depression in the hippocampal CA1 region. J. Neurochem. 96, 179-194.
44. Huang, Z.J., Kirkwood, A., Pizzorusso, T., Porciatti, V., Morales, B., Bear, M.F., Maffei, L., and Tonegawa, S. (1999). BDNF regulates the maturation of Inhibition and the critical period of plasticity in mouse visual cortex. Cell 98, 739-755.
45. Hussman, J.P., Chung, R.H., Griswold, A.J., Jaworski, J.M., Salyakina, D., Ma, D., Konidari, I., Whitehead, P.L., Vance, J.M., Martin, E.R., Cuccaro, M.L., Gilbert, J.R., Haines, J.L. and Pericak-Vance, M.A. (2011). A noise-reduction GWAS analysis implicates altered regulation of neurite outgrowth and guidance in autism. Mol. Autism 2, 1.
46. Isaac, J.T.R., Nicoli, R.A., and Malenka, R.C. (1995). Evidence for silent synapses: Implications for the expression of LTP. Neuron 15, 427-434.
47. Kalb, R.G., and Hockfield, S. (1990). Induction of a neuronal proteoglycan by the NMDA receptor in the developing spinal cord. Science 250, 294-296.
48. Lensjo, K.K., Lepperod, M.E., Dick, G., Hafting, T., and Fyhn, M. (2017). Removal of perineuronal nets unlocks juvenile plasticity through network mechanisms of decreased inhibition and increased gamma activity. J. Neurosci. 37, 1269-1283.
49. Levelt, C.N., and Hubener, M. (2012). Critical-period plasticity in the visual cortex. Annu. Rev. Neurosci. 35, 309-330.
50. Liao, D., Hessler, N.A., and Mallnow, R. (1995). Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice. Nature 375, 400-404.
51. Logothetis, N.K., Eschenko, O., Murayama, Y., Augath, M., Steudel, T., Evrard, H.C., Besserve, M., and Oeltermann, A. (2012). Hippocampal-cortical interaction during periods of subcortical silence. Nature 491, 547-553.
52. Luscher, C., and Malenka, R.C. (2012). NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD). Cold Spring Harb. Perspect. Biol. 4, 1-15.
53. MacGregor, E.A., and Browness, J.M. (1971). Interaction of proteoglycans and chondroitin sulfates with calcium or phosphate ions. Can. J. Biochem. 49, 417-426.
54. Man, H.Y. (2011). GluA2-lacking, calcium-permeable AMPA receptors-inducers of plasticity? Curr, Opin, Neurobiol, 21, 291-298.
55. Martel, M.A., Wyllie, D.J., and Hardingham, G.E. (2009). In developing hippocampal neurons, NR2B-containing N-methyl-D-aspartate receptors (NMDARs) can mediate signaling to neuronal survival and synaptic potentiation, as well as neuronal death. Neuroscience 158, 334-343.
56. Massey, P.V., Johnson, B.E., Moult, P.R., Auberson, Y.P., Brown, M.W., Molnar, E., Collingridge, G.L., and Bashir, Z.I. (2004). Differential roles of NR2A and NR2B-containing NMDA receptors in cortical long-term potentiation and long-term depression. J. Neurosci. 24, 7821-7828.
57. Mayford, M., Wang, J., Kandel, E.R., and O'Dell, T.J. (1995). CaMKII regulates the frequency-response function of hippocampal synapses for the production of both LTD and LTP. Cell 81, 891-904.
58. McCloy, R.A., Rogers, S., Caldon, C.E., Lorca, T., Casttro, A. and Burgess, A. (2014). Partial inhibition of Cdk1 in G2 phase overrides the SAC and decouples mitotic events. Cell Cycle 13, 1400-1412.
59. McRae, P.A., Baranov, E., Sarode, S., Brooks-Kayal, A.R., and Porter, B.E. (2010). Aggrecan expression, a component of the inhibitory interneuron perineuronal net, is altered following an early-life seizure. Neurobiol. Dis. 39, 439-448.
60. McRae, P. A. and Porter, B. E. (2012). The perineuronal net component of the extracellular matrix in plasticity and epilepsy. Neurochem. Int. 61, 963-972.
61. Milner, A.J., Cummings, D.M., Spencer, J.P., and Murphy, K.P. (2004). Bi-directional plasticity and age-dependent long-term depression at mouse CA3-CA1 hippocampal synapses. Neurosci. lett. 367, 1-5.
62. Molley, S.S., and Kennedy, M.B. (1991). Autophosphorylation of type II Ca2+/calmodulin-dependent protein kinase in cultures of postnatal rat hippocampal slices. Proc. Natl. Acad. Sci. U.S.A 88, 4756-4760.
63. Morawski, M., Reinert, T., Meyer-Klaucke, W., Wagner, F.E., Troger, W., Reinert, A., Jager, C., Bruckner, G., and Arendt, T. (2015). Ion exchanger in the brain: Quantitative analysis of perineuronally fixed anionic binding sites suggests diffusion barriers with ion sorting properties. Sci. Rep. 5, 16471-16479.
64. Mulkey, R.M., and Malenka, R.C. (1992). Mechanisms underlying induction of homosynaptic long-term depression. Neuron 9, 967-975.
65. Muller, D., Oliver, M., and Lynch, G. (1989). Developmental changes in synaptic properties in hippocampus of neonatal rats. Dev. Brain Res. 49, 105-104.
66. Niell, C.M., and Stryker, M.P. (2010). Modulation of visual responses by behavioral state in mouse visual cortex. Neuron 65, 472-479.
67. Pinar, C., Fontaine, C.J., Trivino-Paredes, J., Lottenberg, C.P., Gil-Mohapel, J., and Christie, B.R. (2017). Revisiting the flip side: Long-term depression of synaptic efficacy in the hippocampus. Neurosci. Biobehav. Rev. 80, 394-413.
68. Pizzorusso, T., Medini, P., Berardi, N., Chierzi, S., Fawcett, J., and Lamberto, M. (2002). Reactivation of ocular dominance plasticity in the adult visual cortex. Science 298, 1248-1251.
69. Porcher, C., Hatchett, C., Longbottom, R.E., McAinch, K., Sihra, T.S., Moss, S.J., Thomson, A.M., and Jovanovic, J.N. (2011). Positive feedback regulation between gamma-aminobutyric acid type A (GABAA) receptor signaling and brain-derived neurotrophic factor (BDNF) release in developing neurons. J. Biol. Chem. 286, 21667-21677.
70. Renger, J.J., Egles, C., and Liu, G. (2001). A developmental switch neurotransmitter flux enhances synaptic efficacy by affecting ampar receptor activation. Neuron 29, 469-474.
71. Rhodes, K.E., and Fawcett, J. (2004). Chondroitin sulphate proteoglycans- preventing plasticity or protecting the CNS? J. Anat. 204, 33-48.
72. Romberg, C., Yang, S., Melani, R., Andrews, M.R., Horner, A.E., Spillantini, M.G., Bussey, T.J., Fawcett, J.W., Pizzorusso, T., and Saksida, L.M. (2013). Depletion of perineuronal nets enhances recognition memory and long-term depression in the perirhinal cortex. J. Neurosci. 33, 7057-7065.
73. Rosen, K.M., Moghekar, A., and O'Brien, R.J. (2007). Activity dependent localization of synaptic NMDA receptors in spinal neurons. Mol. Cell. Neurosci. 34, 578-591.
74. Rozenberg, F., Robain, O., Jardin, L., and Ben-Ari, Y. (1989). Distribution of GABAergic neurons in late fetal and early postnatal rat hippocampus. Dev. Brain Res. 50, 177-187.
75. Schlingloff, D., Kali, S., Freund, T.F., Hajos, N., and Gulyas, A.I. (2014). Mechanisms of sharp wave initiation and ripple generation. J. Neurosci. 34, 11385-11398.
76. Sernagor, E., Chabrol, F., Bony, G., and Cancedda, L. (2010). GABAergic control of neurite outgrowth and remodeling during development and adult neurogenesis: general rules and differences in diverse systems. Front. Cell Neurosci. 4, 1-11.
77. Slaker, M., Churchill, L., Todd, R.P., Blacktop, J.M., Zuloaga, D.G., Raber, J., Darling, R.A., Brown, T.E., and Sorg, B.A. (2015). Removal of perineuronal nets in the medial prefrontal cortex impairs the acquisition and reconsolidation of a cocaine-induced conditioned place preference memory. J. Neurosci. 35, 4190-4202.
78. Sohal, V.S., Zhang, F., Yizhar, O., and Deisseroth, K. (2009). Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. Nature 459, 698-702.
79. Sorg, B.A., Berretta, S., Blacktop, J.M., Fawcett, J.W., Kitagawa, H., Kwok, J.C., and Miquel, M. (2016). Casting a wide net: role of perineuronal nets in neural plasticity. J. Neurosci. 36, 11459-11468.
80. Spijker, H.M., and Kwok, J.C.F. (2017). A sweet talk: the molecular systems of perineuronal nets in controlling neuronal communication. Front. Int. Neurosci. 11, 33-42.
81. Steel, P.M., and Mauk, M.D. (1999). Inhibitory control of LTP and LTD: Stability of synapse strength. J. Neurophysiol. 81, 1559-1566.
82. Steigerwald, F., Schulz, T.W., Schenker, L.T., Kennedy, M.B., Seeburg, P. H. and Kohr, G. (2000). C-terminal truncation of NR2A subunits impairs synaptic but not extrasynaptic localization of NMDA receptors. J. Neurosci. 20, 4573-4581.
83. Sun, Z., Bozzelli, P.L., Caccavano, A., Allen, M., Balmuth, J., Vicini, S., Wu, J., and Conant, K. (2017). Disruption of perineuronal nets increases the frequency of sharp wave ripple events. Hippocampus 28, 42-52.
84. Frost, D.O., and Hockfield, S. (1988). Expression of a surface-associated antigen on Y-cells in the cat lateral geniculate nucleus is regulated by visual experience. J. Neurosci. 8, 874-882.
85. Svoboda, K.R., and Lupica, C.R. (1998). Opiod inhibition of hippocampal interneurons via modulation of potassium and hyperpolarization-activated cation (Ih) currents. J. Neurosci. 18, 7084-7098.
86. Swann, J.W., Brady, R.J., and Martin, D.L. (1989). Postnatal development of GABA-mediated synaptic inhibition in rat hippocampus. Neuroscience 28, 551-561.
87. Barrionuev, G., and Berger, T.W. (1994). Excitatory stimulation during postsynaptic inhibition induces long-term depression in hipocampus in vivo. J. Neurophysio. 72, 3009-3015.
88. Tan, C.L., Kwok, JC.F., Patani, R., Chandran, S. and Fawcett, JW. (2011). Integrin activation promotes axon growth on inhibitory CSPGs by enhancing integrin signaling. J. Neurosci. 31, 6289-6295.
89. Tsai, T.C., Huang, C.C., and Hsu, K.S. (2018). Infantile amnesia is related to developmental immaturity of the maintenance mechanisms for long-term potentiation. Mol. Neurobiol. 18, 1119-1124.
90. Volman, V., Behrens, M.M. and Sejnowski, T.J. (2011). Downregulation of parvalbumin at cortical GABA synapses reduces network gamma oscillatory activity. J. Neurosci. 31, 18137-18148.
91. Wagner, J.J., and Alger, B.E. (1995). GABAergic and developmental influences on homosynaptic LTD and depotentiation in rat hippocampus. J Neurosci 15, 1577-1586.
92. Wang, D., and Fawcett, J. (2012). The perineuronal net and the control of CNS plasticity. Cell Tiss. Res. 349, 147-160.
93. Weiss, L.A., Arking, D.E., Gene Discovery Project of Johns Hopkins&the Autism Consortium, Daly, M.J. and Chakravarti, A. (2009). A genome-wide linkage and association scan reveals novel loci for autism. Nature 461, 802– 808.
94. Wigstrom, H., and Gustafsson, B. (1985). Facilitation of hippocampal long-lasting potentiation by GABA antagonists. Acta. Physiologica. 125, 159-172.
95. Wong, J.M., and Gray, J.A. (2018). Long-term depression is independent of GluN2 subunit composition. J. Neurosci. 38, 4462-4470.
96. Yamada, J., and Jinno, S. (2013). Spatio-temporal differences in perineuronal net expression in the mouse hippocampus, with reference to parvalbumin. Neuroscience 253, 368-379.
97. Yang, S., Cacquevel, M., Saksida, L.M., Bussey, T.J., Schneider, B.L., Aebischer, P., Melani, R., Pizzorusso, T., Fawcett, J.W. and Spillantini, M.G. (2015). Perineuronal net digestion with chondroitinase restores memory in mice with tau pathology. Exp. Neurol. 265, 48 –58.
98. Yang, C.H., Huang, C.C., Hsu, K.S. (2005). Behavioral stress enhances hippocampal CA1 long-term depression through the blockade of the glutamate uptake. J. Neurosci. 25, 4288-4293.
99. Yang, S.S., Li, Y.C., Coley, A.A., Chamberlin, L.A., Yu, P., and Gao, W.J. (2018). Cell-type specific development of the hyperpolarization-activated current, Ih, in prefrontal cortical neurons. Front. Syn. Neurosci. 10, 1-7.
100. Yu, X., Duan, K.L., Shang, C.F., Yu, H.G., and Zhou, Z. (2004). Calcium influx through hyperpolarization-activated cation channels (Ih channels) contributes to activity-evoked neuronal secretion. Proc. Natl. Acad. Sci. U.S.A 101, 1051-1056.
101. Zhang, M.-M., Xiao, C., Yu, K., and Ruan, D.-Y. (2003). Effects of sodium valproate on synaptic plasticity in the CA1 region of rat hippocampus.Food Chem. Toxicol. 41, 1617-1623.
102. Zhao, J.P., and Constantine-Paton, M. (2007). NR2A-/- mice lack long-term potentiation but retain NMDA receptor and L-type Ca2+ channel-dependent long-term depression in the juvenile superior colliculus. J. Neurosci. 27, 13649-13654.
103. Zhou, Z., Liu, A., Xia, S., Leung, C., Qi, J., Meng, Y., Xie, W., Park, P., Collingridge, G.L., and Jia, Z. (2018). The C-terminal tails of endogenous GluA1 and GluA2 differentially contribute to hippocampal synaptic plasticity and learning. Nat. Neurosci. 21, 50-62.