The potential of caffeine for functional modification from cortical synapses to neuron networks in the brain

Structure and function of the brain are use-dependent variables based on "synapse plasticity". Since synapses are driven by chemical transmitters, synaptic functions are liable to be modified by extrinsic chemicals displaying affinities for synaptic receptors or modulators. Caffeine is a widely used chemical substance that can invade synapses, and has several biochemical and metabolic actions on synaptic activities. This review focuses on the actions of caffeine on changes in structure and function in the region of the hippocampal formation and neocortex, which exhibit high synapse plasticity. At the synapse level, various synaptic receptors and channel activities are modulated by caffeine via mobilization of intracellular calcium, inhibition of phosphodiesterase, antagonism of adenosine receptors and GABA receptors. These actions of caffeine enable neurons to induce plastic changes in the properties of synaptic activities, such as synaptic transmission efficiency and morphology. At the network level, caffeine has the ability to activate cortical neural oscillators that deliver repetitive N-methyl-D-aspartate receptor-dependent signals to surrounding areas, causing strengthening of long-range inter-cortical communications. Caffeine might thus allow reorganization of cortical network functions via synaptic mobilizations.