Synaptic Plasticity is assumed by neuroscientists to be the key to an understanding of the complex functions of our brain. By “Plasticity” of synaptic connections we mean the fact that the coupling strengths between individual neurons are not constant, but keep changing, while information is processed by the system. Changes in synaptic strength occur on all time scales. Some of them are imprinted for the rest of an individual’s life – these and other long-term changes are believed to underlie learning and memory. Other changes happen on the seconds and sub-seconds time scale and cause the constant “rewiring” of our neuronal circuits, while we adapt to sensory inputs or recall memory. When we study synaptic transmission, we therefore not only want to uncover the mechanisms, by which neurotransmitter is released and how it acts on the postsynaptic membrane, but also why synaptic strength changes in a use-dependent manner.

It turns out that nature uses all the mechanisms of cellular regulation, which it has developed during evolution, to solve the task of providing synaptic plasticity on so many time scales. Morphological changes consolidate the long-term effects; changes in gene expression act on intermediate time scales; protein phosphorylation / dephosphorylation and changes in ion concentrations and second messenger concentrations mediate the short to ultrashort effects.

My laboratory has been studying synaptic transmission and short-term synaptic plasticity at the Calyx of Held - a synapse in the brainstem, which relays auditory information. It is a glutamateric, excitatory synapse, which offers the advantage that it is accessible to rigorous biophysical analysis. Recently, we were asking the question, how slow “modulatory” transmitter systems influence the glutamate release from the presynaptic terminal of this synapse. Such “slow” transmitters act through presynaptic receptors, which stimulate second messenger systems (such as involving G-protein coupled receptors, adenylate cyclase, and cyclic AMP) and thereby lead to short-term plastic changes. One effect of such a cascade employing GABAB-receptors had been known before – the down-modulation of the presynaptic Ca-influx, leading to a potent suppression of the transmitter release. We found that, in addition, the activation of GABAB-receptors slows down the recovery of the synapse after strong stimulation and following “short-term depression”. In this signal pathway calcium and cAMP cooperate to regulate the availability of synaptic vesicles for release. The multiplicity of the signal flow allows for differential regulation of synaptic strength, depending on the frequency of usage of a given synapse, and, therefore is expected to be important for understanding short-term plasticity and its influence on the behaviour of neuronal networks.