Similar presynaptic action potential-calcium influx coupling in two types of large mossy fiber terminals innervating CA3 pyramidal cells and hilar mossy cells.

Morphologically similar axon boutons form synaptic contacts with diverse types of postsynaptic cells. However, it is less known to what extent the local axonal excitability, presynaptic action potentials and AP-evoked calcium influx contribute to the functional diversity of synapses and neuronal activity. This is particularly interesting in synapses that contact cell types that show only subtle cellular differences but fulfill completely different physiological functions. Here we tested these questions in two synapses that are formed by rat hippocampal granule cells onto hilar mossy cells and CA3 pyramidal cells, which albeit share several morphological and synaptic properties but contribute to distinct physiological functions. We were interested in the deterministic steps of the action potential-calcium ion influx coupling as these complex modules may underlie the functional segregation between and within the two cell types. Our systematic comparison using direct axonal recordings showed that AP shapes, Ca 2+ currents and their plasticity are indistinguishable in synapses onto these two cell types. These suggest that the complete module that couples granule cell activity to synaptic release is shared by hilar mossy cells and CA3 pyramidal cells. Thus, our findings present an outstanding example for the modular composition of distinct cell types, by which cells employ different components only for those functions that are deterministic for their specialized functions, while many of their main properties are shared. Significance statement How different neurons should be for distinct functionality? Several examples showed that distinct neuron types use identical ion channels or synaptic proteins in various combinations to achieve cell type-specific excitability or synaptic properties. But what about complete modules, in which mechanisms cooperate for fundamental functions, such as the AP-I Ca coupling that translates presynaptic activity to Ca 2+ influx that triggers synaptic release. Do cell type-specific functions determine the operation of modules? Here we examined AP-I Ca coupling in the common synaptic drive to CA3 pyramidal cells and hilar mossy cells, which contribute to distinct hippocampal functions. We revealed that their main excitatory synapses from granule cells share all components of AP-I Ca coupling, demonstrating that distinct cell types can utilize identical synaptic modules.