E35. The method of embodiment 33, wherein the molecule is administered to the brain of the mammal. E49. The method of embodiment 48, wherein the disease or a condition is selected from the group consisting of a viral infection, a neurological disorder (e.g., Alzheimer's disease, progressive supranuclear palsy, Down syndrome, dementia pugilistica (chronic traumatic encephalopathy and other traumatic brain injury), frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), Huntington's disease, Rett Syndrome, Angelman Syndrome, Lytico-Bodig disease (Parkinson-dementia complex of Guam), Tangle-predominant dementia, ganglioglioma, gangliocytoma, meningioangiomatosis, subacute sclerosing panencephalitis, lead encephalopathy, Hemimegalencephaly, tuberous sclerosis, Hallervorden-Spatz disease, Pick's disease, corticobasal ganglionic degeneration, argyrophilic grain disease, corticobasal degeneration, lipofuscinosis, frontotemporal dementia, supranuclear palsy, and frontotemporal lobar degeneration, a disease of brain network dysfunction (e.g., all forms of epilepsy and depression), a spinal cord disorder, a peripheral neuropathy, a cranial nerve disorder (e.g., Trigeminal neuralgia), an autonomic nervous system disorder (e.g., dysautonomia or multiple system atrophy), a movement disorder of a central and peripheral nervous system (e.g., Parkinson's disease, essential tremor, amyotrophic lateral sclerosis, Tourette's Syndrome, multiple sclerosis or various types of peripheral neuropathy), a sleep disorder (e.g., Narcolepsy), migraine or other types of headache (e.g., cluster headache and tension headache), lower back and neck pain, central neuropathy, a neuropsychiatric illness, attention deficit hyperactivity disorder, autism, Huntington's disease, organic psychosis, an infection of the brain or spinal cord (including meningitis), or a prion disease), anemia, cancer, leukemia, an inflammatory condition or an autoimmune disease (e.g. arthritis, psoriasis, lupus erythematosus, multiple sclerosis), a bacterial infection, frontotemporal dementia-tau (FTD-tau), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), watch live sexcam corticobasal degeneration (CBD), traumatic brain injury, chronic traumatic encephalopathy, Watchlivesexcam.Com HIV associated neurocognitive disorders, Argyrophilic grain disease, Down syndrome-Alzheimer's disease, Amnestic mild cognitive impairment-Alzheimer's disease, Parkinson's disease dementia, Hallervorden-Spatz disease (Pantothenate kinase-associated neurodegeneration), Niemann Pick disease type C, Myotonic dystrophy, Amyotrophic lateral sclerosis, Hemimegalencephaly, Tuberous sclerosis complex, Focal cortical dysplasia type 2b, Ganglion cell tumors, Dravet Syndrome (severe myoclonic epilepsy of infancy), Temporal lobe epilepsy, Ohtahara syndrome (early infantile epileptic encephalopathy with suppression bursts), Lafora body disease, Generalized epilepsy with febrile seizures, Infantile spasms (West syndrome), Lennox Gastaut syndrome, Angelman Syndrome, Rett Syndrome, Landau Kleffner syndrome, focal seizures, simple focal seizures (no loss of consciousness), focal dyscognitive seizures (impairment of consciousness), focal seizure evolving to generalised tonic-clonic (GTC) convulsions, generalised seizures (convulsive or non-convulsive with bilateral discharges involving subcortical structures), watch live sexcam absence seizures, myoclonic seizures, clonic seizures, tonic seizures, tonic-clonic seizures and atonic seizures, an autistic disorder, an autism spectrum disorder, an Asperger's disorder, a pervasive developmental disorder, and any combination thereof.



E78. The molecule of Embodiment 77, wherein the disease or condition is associated with a neuronal cell. E62. The method of embodiment 61, wherein the disease or condition associated with a neuronal cell. E48. The method of any one of embodiments 1 to 47, further comprising administering the molecule to a subject in need of treatment for a disease or condition. E79. An antisense oligonucleotide for use in treating a neurological disease or condition in a subject in need thereof, wherein calcium oscillations in neuronal cells that are in contact with the antisense oligonucleotide are about 70% or higher, about 75% or higher, about 80% or higher, about 85% or higher, about 90% or higher, about 95% or higher, about 96% or higher, about 97% or higher, about 98% or higher, about 99% or higher, about 100% or higher, about 120% or higher, about 140% or higher, about 160% or higher, about 180% or higher, about 200% or higher, about 220% or higher, about 240% or higher, or about 250% or higher compared to the calcium oscillations in vehicle control cells.



E50. The method of embodiment 49, wherein the molecule treats or prevents a disease or condition. 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. E34. The method of embodiment 33, wherein the in vivo tolerability is measured by administering the molecule to a mammal and grading the mammal's tolerability in a tolerability category. 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. 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 less than about 1% of the tubulin intensity in the culture of neuronal cells.



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. E65. The method of Embodiment 63 or 64, wherein the neuronal cells are prepared from mammalian cortical neurons. E28. The method of embodiment 27, wherein the mRNA is expressed in a neuronal cell. E27. The method of any one of embodiments 25 to 26, wherein the mRNA is expressed in a cell. E53. The method of any one of embodiments 16 to 52, wherein the polynucleotide comprises at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten nucleotide analogs. E37. The method of any one of embodiments 34 to 36, wherein the tolerability category comprises at least one, at least two, at least three, at least four, or at least five tolerability categories. E87. In the method of any one of Embodiments 81 to 85, the improvement further comprising measuring an in vivo tolerability 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.



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. 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. E32. The method of any one of embodiments 1 to 31, further measuring reduction of in vitro expression of a target protein of the molecule. 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. 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").