Modeling of the Glutamatergic Synaptic Transmission and its Modulation by Adenosine and Caffeine

ABSTRACT

A quantitative description of the adenosine and caffeine influence on the glutamatergic synaptic neurotransmission is presented. The analysis is based on a set of coupled mathematical models for a sequence of processes involved in the synaptic transmission, starting from the action potential at the presynaptic axonal terminal and up to the spike generation at the postsynaptic membrane. Adenosine and caffeine act via binding to the presynaptic adenosine receptors that results in the alteration of axon terminal calcium ion influx and, thereby, in the modulation of the efficiency of neurotransmitter release. Dynamics of the glutamate in the synaptic cleft were determined taking into account its release from the presynaptic vesicles with subsequent glutamate diffusion and reuptake. Maximal value of the glutamate concentration in the cleft is about 1.2 mM. The glutamate content elevation induces a spike at the postsynaptic neuron. The dependence of the synaptic transmission efficiency on the levels of adenosine and caffeine has been analyzed. The probability of the synaptic transmission is increased from 0.3 to about 0.5 when varying caffeine concentration from 0 to 200 µM. Transmission probability significantly depends on the number of the postsynaptic glutamate receptors.