ABSTRACT
The short-term dynamics of synaptic communication between neurons provides neural networks with specific frequency-filter characteristics for information transfer. The direction of short-term synaptic plasticity, that is, facilitation versus depression, is highly dependent on and inversely correlated to the basal release probability of a synapse. Amongst the processes implicated in shaping the release probability, proteins that regulate the docking and priming of synaptic vesicles at the active zone are of special importance. Here, we found that a member of the Munc13 protein family of priming proteins, namely Munc13-2, is essential for normal release probability at hippocampal mossy fiber synapses. Paired pulse and frequency facilitation were strongly increased, whereas mossy fiber long-term potentiation was unaffected in the absence of Munc13-2. In contrast, transmission at 3 other types of hippocampal synapses, Schaffer-collateral, associational-commissural, as well as inhibitory synapses onto CA3 pyramidal neurons was unaffected by the loss of Munc13-2.
Subject(s)
Hippocampus/cytology , Intracellular Signaling Peptides and Proteins/metabolism , Nerve Tissue Proteins/metabolism , Neuronal Plasticity/genetics , Neuronal Plasticity/physiology , Synapses/physiology , Animals , Animals, Newborn , Calcium/metabolism , Cyclopropanes/pharmacology , Dipeptides/pharmacology , Electric Stimulation/methods , Excitatory Amino Acid Antagonists/pharmacology , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/genetics , GABA Antagonists/pharmacology , Glycine/analogs & derivatives , Glycine/pharmacology , In Vitro Techniques , Intracellular Signaling Peptides and Proteins/deficiency , Long-Term Potentiation/drug effects , Long-Term Potentiation/genetics , Mice , Mice, Knockout , Mossy Fibers, Hippocampal/drug effects , Mossy Fibers, Hippocampal/physiology , Nerve Tissue Proteins/deficiency , Neuronal Plasticity/drug effects , Patch-Clamp Techniques/methods , Pyridazines/pharmacology , Quinoxalines/pharmacology , Synapses/drug effectsABSTRACT
The modulation of synaptic transmission by presynaptic ionotropic and metabotropic receptors is an important means to control and dynamically adjust synaptic strength. Even though synaptic transmission and plasticity at the hippocampal mossy fibre synapse are tightly controlled by presynaptic receptors, little is known about the downstream signalling mechanisms and targets of the different receptor systems. In the present study, we identified the cellular signalling cascade by which adenosine modulates mossy fibre synaptic transmission. By means of electrophysiological and optical recording techniques, we found that adenosine activates presynaptic A1 receptors and reduces Ca2+ influx into mossy fibre terminals. Ca2+ currents are directly modulated via a membrane-delimited pathway and the reduction of presynaptic Ca2+ influx can explain the inhibition of synaptic transmission. Specifically, we found that adenosine modulates both P/Q- and N-type presynaptic voltage-dependent Ca2+ channels and thereby controls transmitter release at the mossy fibre synapse.
