Antisense oligomer inhibition of spontaneous calcium oscillations mediated by either NMDA or AMPA was assessed in the presence or absence of 1 mM MgCl.sub.2 (representing 100% control in each case). FIG. 2: Graph showing inhibition of AMPA mediated calcium oscillations by antisense oligomers as an indication of neuronal network activity disruption. The ASO and other oligomerss that behaved similarly, were shown to negatively impact central nervous system (CNS) network activity in vivo and electrophysiologic spontaneous neuronal activity in vitro (data not shown). Calcium oscillations were reduced further, by about 80%, when N-methyl-D-aspartate (NMDA) receptor function was blocked by 1 mM MgCl.sub.2 (NMDA labeled bar shown). E81. In a method of testing or determining in vivo neurotoxicity of a molecule, the improvement comprising measuring calcium oscillations in vitro in neuronal cells which are in contact with the molecule. E45. The method of any one of embodiments 1 to 44, further comprising measuring tubulin intensity of the molecule in a culture of neuronal cells. E63. A method of testing or determining in vivo acute neurotoxicity of a molecule comprising the steps of 1) adding the molecule to a culture of neuronal cells and 2) measuring calcium oscillations in vitro in the neuronal cells.



E46. The method of embodiment 45, wherein the tubulin intensity of the molecule is compared to the tubulin intensity in neuronal cells not exposed to the molecule. E64. The method of Embodiment 63, further comprising comparing the calcium oscillations in the neuronal cells with the calcium oscillations in neuronal cells that are not exposed to the molecule ("control cells"). E65. The method of Embodiment 63 or 64, wherein the neuronal cells are prepared from mammalian cortical neurons. E62. The method of embodiment 61, wherein the disease or condition associated with a neuronal cell. E47. The method of embodiment 46, wherein the molecule reduces less than about 25%, less than about 20%, less than about 15%, less than about 10%, less than about 5%, or https://watchlivesexcam.Com less than about 1% of the tubulin intensity in the culture of neuronal cells. E82. In a method of selecting or identifying a molecule having tolerable in vivo neurotoxicity, the improvement comprising measuring calcium oscillations in vitro in neuronal cells which are in contact with the molecule, wherein the neuronal cells in contact with the molecule exhibit calcium oscillations at a level comparable to or higher than that of vehicle control cells. E87. In the method of any one of Embodiments 81 to 85, the improvement further comprising measuring an in vivo tolerability of the molecule.





E69. The method of any one of Embodiments 63 to 68, wherein the molecule comprises a small molecule, a polynucleotide, a protein, a peptide, or any combination thereof. E44. The method of any one of embodiments 41 to 43, wherein the behavioral test is a short term memory test, a spatial learning and memory test, a gait analysis test, or any combination thereof. E88. In the method of Embodiment 87, wherein the in vivo tolerability is measured by administering the molecule to a mammal and grading the mammal's tolerability in a tolerability category. E36. A method of testing or determining in vivo tolerability of a molecule comprising administering the molecule to a mammal and grading the mammal's tolerability in a tolerability category. E35. The method of embodiment 33, wherein the molecule is administered to the brain of the mammal. E57. The method of any one of embodiments 1 to 56, wherein when the molecule is administered to laboratory animals, more than 20% of the animals survive.



E59. The method of any one of embodiments 1 to 58, wherein when the molecule is administered to laboratory animals, more than 85% of the animals survive. E76. The method of any one of Embodiments 63 to 74, wherein when the molecule is administered to laboratory animals, more than 85% of the animals survive. E58. The method of any one of embodiments 1 to 57, wherein when the molecule is administered to laboratory animals, more than 50% of the animals survive. E75. The method of any one of Embodiments 63 to 74, wherein when the molecule is administered to laboratory animals, more than 50% of the animals survive. E42. The method of any one of embodiments 1 to 41, further comprising measuring a behavioral test score of the molecule. E86. In the methods of Embodiments 81 to 85, the improvement further comprising measuring reduction of in vitro expression of a target protein of the molecule.