Distinct release properties of glutamate/GABA co-transmission serve as a frequency-dependent filtering of supramammillary inputs.

Glutamate and GABA co-transmitting neurons exist in several brain regions; however, the mechanism by which these two neurotransmitters are co-released from the same synaptic terminals remains unclear. Here, we show that the supramammillary nucleus (SuM) to dentate granule cell synapses, which co-release glutamate and GABA, exhibit differences between glutamate and GABA release properties in paired-pulse ratio, Ca-sensitivity, presynaptic receptor modulation, and Ca channel-vesicle coupling configuration. Moreover, uniquantal synaptic responses show independent glutamatergic and GABAergic responses.

Mechanistic insights into cAMP-mediated presynaptic potentiation at hippocampal mossy fiber synapses.

Presynaptic plasticity is an activity-dependent change in the neurotransmitter release and plays a key role in dynamic modulation of synaptic strength. Particularly, presynaptic potentiation mediated by cyclic adenosine monophosphate (cAMP) is widely seen across the animals and thought to contribute to learning and memory. Hippocampal mossy fiber-CA3 pyramidal cell synapses have been used as a model because of robust presynaptic potentiation in short- and long-term forms.

Increased vesicle fusion competence underlies long-term potentiation at hippocampal mossy fiber synapses.

Presynaptic long-term potentiation (LTP) is thought to play an important role in learning and memory. However, the underlying mechanism remains elusive because of the difficulty of direct recording during LTP. Hippocampal mossy fiber synapses exhibit pronounced LTP of transmitter release after tetanic stimulation and have been used as a model of presynaptic LTP.

Subcortical glutamatergic inputs exhibit a Hebbian form of long-term potentiation in the dentate gyrus.

The hippocampus receives glutamatergic and GABAergic inputs from subcortical regions. Despite the important roles of these subcortical inputs in the regulation of hippocampal circuit, it has not been explored whether associative activation of the subcorticohippocampal pathway induces Hebbian plasticity of subcortical inputs. Here, we demonstrate that the hypothalamic supramammillary nucleus (SuM) to the dentate granule cell (GC) synapses, which co-release glutamate and GABA, undergo associative long-term potentiation (LTP) of glutamatergic, but not GABAergic, co-transmission.