25. Li Y, Zhou W, Xiangning L, Shaoqun Z, Man L, et al. (2007) Characterization of synchronized bursts in cultured hippocampal neuronal networks with learning training on microelectrode arrays. Biosensors and Bioelectronics 22: 12, 2976– 2982. 26. Zhang JY, Yan GT, Liao J, Deng ZH, Xue H, et al. (2011) Leptin attenuates cerebral ischemia/reperfusion injury partially by CGRP expression. European Journal of Pharmacology 671(1–3): 61–9. 27. Meloni BP, Meade AJ, Kitikomolsuk D, Knuckey NW (2011) Characterisation of neuronal cell death in acute and delayed in vitro ischemia (oxygen-glucose deprivation) models. Journal of Neuroscience Methods 195(1): 67–74. 28. Huang L, Li Q, Li H, He Z, Cheng Z, et al. (2009) Inhibition of intracellular Ca2+ release by a Rho-kinase inhibitor for the treatment of ischemic damage in primary cultured rat hippocampal neurons. European Journal of Pharmacology 602(2–3): 238–44. 29. Jayalakshmi K, Sairam M, Singh SB, Sharma SK, Ilavazhagan G, et al. (2005) Neuroprotective effect of N-acetyl cysteine on hypoxia-induced oxidative stress in primary hippocampal culture. Brain Research 1046(1–2): 97–104. 30. O’Malley D, Irving AJ, Harvey J (2005) Leptin-induced dynamic alterations in the actin cytoskeleton mediate the activation and synaptic clustering of BK channels. FASEB Journal 19(13): 1917–9. 31. Swensen AM, Bean BP (2003) Ionic mechanisms of burst firing in dissociated Purkinje neurons. Journal of Neuroscience 22;23(29): 9650–63. 32. Wagenaar DA, Madhavan R, Pine J, Potter SM (2005) Controlling bursting in cortical cultures with closed-loop multi-electrode stimulation. Journal of Neuroscience 25(3): 680–8. 33. Overton PG, Clark D (1997) Burst firing in midbrain dopaminergic neurons. Brain Research Reviews 312–334. 34. Chen C, Chen L, Lin Y, Zeng S, Luo Q (2006) The origin of spontaneous synchronized burst in cultured neuronal networks based on multi-electrode arrays. Biosystems 85(2): 137–43. 35. Cohen D, Segal M (2011) Network bursts in hippocampal microcultures are terminated by the exhaustion of vescicles pools. Journal of Neurophysiology 106(5): 2314–21. 36. Blankenship AG, Feller MB (2010) Mechanisms underlying spontaneous patterned activity in developing neural circuits. Nature Reviews Neuroscience 11(1): 18–29. 37. Yamamoto S, Tanaka E, Higashi H (1997) Mediation by intracellular calcium- dependent signals of hypoxic hyperpolarization in rat hippocampal CA1 neurons in vitro. Journal of Neurophysiology 77(1): 386–92. 38. Lukyanetz EA, Shkryl VM, Kravchuk OV, Kostyuk PG (2003) Action of hypoxia on different types of calcium channels in hippocampal neurons. Biochimica et Biophysica Acta 1618(1): 33–8. 39. Gala´n RF, Dick TE, Baekey DM (2010) Analysis and modeling of ensemble recordings from respiratory pre-motor neurons indicate changes in functional network architecture after acute hypoxia. Frontier in Computational Neurosci- ence 4. pii: 131. Hypoxia, Leptin and Hippocampal Neurons Firing 40. Geracitano R, Tozzi A, Berretta N, Florenzano F, Guatteo E, et al. (2005) Protective role of hydrogen peroxide in oxygen-deprived dopaminergic neurones of the rat substantia nigra. Journal of Physiology 568(Pt 1): 97–110. 41. Huang XF, Koutcherov I, Lin S, Wang HQ, Storlien L (1996) Localization of leptin receptor mRNA expression in mouse brain. Neuroreport 7(15–17): 2635– 8. 42. Walker CD, Long H, Williams S, Richard D (2007) Long-lasting effects of elevated neonatal leptin on rat hippocampal function, synaptic proteins and NMDA receptor subunits. Journal of Neuroscience Research 85(4): 816–28. 43. Lieb W, Beiser AS, Vasan RS, Tan ZS, Au R, et al. (2009) Association of plasma leptin levels with incident Alzheimer disease and MRI measures of brain aging. Journal of the American Medical Association 302(23): 2565–72. 44. Merlo S, Spampinato S, Canonico PL, Copani A, Sortino MA (2010) Alzheimer’s disease: brain expression of a metabolic disorder? Trends in Endocrinology and Metabolism 21(9): 537–44. 45. Greco SJ, Bryan KJ, Sarkar S, Zhu X, Smith MA, et al. (2010) Leptin reduces pathology and improves memory in a transgenic mouse model of Alzheimer’s disease. Journal of Alzheimers Disease 19(4): 1155–67. 46. Greco SJ, Hamzelou A, Johnston JM, Smith MA, Ashford JW, et al. (2011) Leptin boosts cellular metabolism by activating AMPK and the sirtuins to reduce tau phosphorylation and b-amyloid in neurons. Biochemical and Biophysical Research Communications 414(1): 170–4. 47. Kumral A, Yesilirmak DC, Sozmen S, Ergur BU, Tugyan K, et al. (2012) Effect of leptin treatment on neonatal hypoxic-ischemic brain injury. Journal of Maternal-Fetal and Neonatal Medicine 25(2): 141–6. 48. Dal-Cim T, Martins WC, Santos AR, Tasca CI (2011) Guanosine is neuroprotective against oxygen/glucose deprivation in hippocampal slices via large conductance Ca2+-activated K+ channels, phosphatidilinositol-3 kinase/ protein kinase B pathway activation and glutamate uptake. Neuroscience 183: 212–20. 49. Liao Y, Kristiansen AM, Oksvold CP, Tuvnes FA, Gu N, et al. (2010) Neuronal Ca2+-activated K+ channels limit brain infarction and promote survival. PLoS One 5(12): e15601. 50. Runde´n-Pran E, Haug FM, Storm JF, Ottersen OP (2002) BK channel activity determines the extent of cell degeneration after oxygen and glucose deprivation: a study in organotypical hippocampal slice cultures. Neuroscience 112(2): 277– 88. 51. Hu H, Shao LR, Chavoshy S, Gu N, Trieb M, et al. (2001) Presynaptic Ca2+- activated K+ channels in glutamatergic hippocampal terminals and their role in spike repolarization and regulation of transmitter release. Journal of Neurosci- ence 21(24): 9585–97. 52. Hepp S, Gerich FJ, Mu¨ ller M (2005) Sulfhydryl oxidation reduces hippocampal susceptibility to hypoxia-induced spreading depression by activating BK channels. Journal of Neurophysiology 94(2): 1091–103. 53. Gribkoff VK, Starrett JE Jr, Dworetzky SI, Hewawasam P, Boissard CG, et al. (2001) Targeting acute ischemic stroke with a calcium-sensitive opener of maxi- K potassium channels. Nature Medicine 7(4): 471–7. PLoS ONE | www.plosone.org 17 July 2012 | Volume 7 | Issue 7 | e41530