RESEARCH

We made the first description of presynaptic mitochondrial Ca2+ uptake in the context of physiological activity (Chouhan et al., 2010, J Neurosci), followed by the first description of the way in which Ca2+ coordinates presynaptic mitochondrial energy metabolism with synaptic activity (Chouhan et al., 2012, J Neurosci; Ivannikov and Macleod, 2013, Biophys J).

Since these studies, we have established a quantitative framework for presynaptic energy efficiency and power demand in situ [Lu et al., 2016, Current Biol; Justs et al., 2022, J Neurosci; Justs et al., 2023, J Physiol], providing the foundation for a thorough understanding of the ways in neurons integrate mitochondrial function with their own function in general and synaptic function in particular.

To investigate the rapid acidification within nerve terminals during endogenous activity, we expressed various pH-sensitive proteins in their cytosol (Rossano et al., 2013, J. Physiol).  We followed up with the first description of a role for vGlut in re-alkalinization of nerve terminals after activity (Rossano et al., 2017, J. Physiol).  We then demonstrated that chemical pH indicators, in addition to pHluorins, could be targeted to the extracellular space of the synaptic cleft (Stawarski et al., 2018, J. Neurogenet) and proceeded to show that the clefts of glutamatergic synapses alkalinize during neurotransmission, rather than acidify (Stawarski et al., 2020, J. Neurosci).  Our recent computational model (Feghhi et al., 2021, Biophys J) reconciles cleft alkalinization with ASIC activation at the very same synapses.