Cell-type specific and nanoscale control of hippocampal presynaptic homeostatic plasticity

The lifelong continuity of neuronal function rests upon the perdurance of neurons, synapses and neural circuits that are sustained, in part, by homeostatic signaling. Currently, the implementation of homeostatic signaling within complex brain circuitry remains poorly defined. Given the tremendous diversity of cell and synapse types, is homeostatic plasticity deployed in a cell-type specific manner and, if so, what are the rules? Here, we report that presynaptic homeostatic plasticity (PHP) is achieved in a target neuron-specific manner. PHP is robust at synapses that contact parvalbumin-positive (PV+) and absent at somatostatin-positive (SST+) interneurons. Furthermore, PHP can be differentially induced at adjacent synapses that are present within single axonal boutons, separated by hundreds of nanometers. These highly localized effects are eliminated in the absence of Sema3A signaling, a homeostatic signaling molecule. Our data suggest a model where PHP is repressed throughout axons that contact SST+ interneurons and locally de-repressed with nanoscale precision.