Synapses, spines and kinases in mammalian learning and memory, and the impact of aging.

Synapses are the building blocks of neuronal networks. Spines, the postsynaptic elements, are morphologically the most plastic part of the synapse. It is thought that spine plasticity underlies learning and memory processes, driven by kinases and cytoskeleton protein reorganization. Spine strength depends primarily on the number of incorporated glutamatergic receptors, which are more numerous in larger spines. Intrinsic and circadian fluctuations, occurring independently of presynaptic stimulation, demonstrate the native instability of spines. Despite innate spine instability some spines remain intact lifelong. Threats to spine survival are reduced by physical and mental activity, and declining sensory input, conditions characteristic for aging. Large spines are considered less vulnerable than thin spines, and in the older brain large spines are more abundant, whereas the thin spines are functionally weaker. It can be speculated that this shift towards memory spines contributes to enhanced retention of remote memories typically seen in the elderly. Gaining further insight in spine plasticity regulation, its homeostatic nature and how to maintain spine health will be important future research topics in Neuroscience.