Population imaging of synaptically released glutamate in mouse hippocampal slices

Glutamatergic neurotransmission is a widespread form of synaptic excitation in the mammalian brain. The development of genetically encoded fluorescent glutamate sensors allows monitoring synaptic signaling in living brain tissue in real time. Here, we describe single- and two-photon imaging of synaptically evoked glutamatergic population signals in acute hippocampal slices expressing the fluorescent glutamate sensor SF-iGluSnFR.A184S in CA1 or CA3 pyramidal neurons. The protocol can be readily used to study defective synaptic glutamate signaling in mouse models of neuropsychiatric disorders, such as Alzheimer disease. For complete details on the use and execution of this protocol, please refer to Zott et al. (2019).