Dosing regimens and methods are disclosed for upregulating on protein kinase C (PKC) while reducing subsequent downregulation, comprising administering a PKC activator once a week for three consecutive weeks followed by cessation of administration or dosing for three consecutive weeks. Also described are methods for improving or enhancing cognitive ability, preventing or treating cognitive impairment, preventing or treating a neurodegenerative disease or condition, and/or preventing or treating a disease or condition associated with neuronal or synaptic loss according to the disclosed regimens.