In a complex and dynamic environment, the brain flexibly adjusts its circuits to preferentially process behaviorally relevant information. Here, we investigated how the olfactory bulb copes with this demand by examining the plasticity of adult-born granule cells (abGCs). We found that learning of olfactory discrimination elevates odor responses of young abGCs and increases their apical dendritic spines. This plasticity did not occur in abGCs during passive odor experience nor in resident granule cells (rGCs) during learning. Furthermore, we found that feedback projections from the piriform cortex show elevated activity during learning, and activating piriform feedback elicited stronger excitatory postsynaptic currents in abGCs than rGCs. Inactivation of piriform feedback blocked abGC plasticity during learning, and activation of piriform feedback during passive experience induced learning-like plasticity of abGCs. Our work describes a neural circuit mechanism that uses adult neurogenesis to update a sensory circuit to flexibly adapt to new behavioral demands.

The endoplasmic reticulum (ER) is a tortuous organelle that spans throughout a cell with a continuous membrane containing ion channels, pumps, and transporters. It is unclear if stimuli that gate ER ion channels trigger substantial membrane potential fluctuations and if those fluctuations spread beyond their site of origin. Here, we visualize ER membrane potential dynamics in HEK cells and cultured rat hippocampal neurons by targeting a genetically encoded voltage indicator specifically to the ER membrane. We report the existence of clear cell-type- and stimulus-specific ER membrane potential fluctuations. In neurons, direct stimulation of ER ryanodine receptors generates depolarizations that scale linearly with stimulus strength and reach tens of millivolts. However, ER potentials do not spread beyond the site of receptor activation, exhibiting steep attenuation that is exacerbated by intracellular large conductance K⁺ channels. Thus, segments of ER can generate large depolarizations that are actively restricted from impacting nearby, contiguous membrane.

Voltage imaging and "all-optical electrophysiology" in human induced pluripotent stem cell (hiPSC)-derived neurons have opened unprecedented opportunities for high-throughput phenotyping of activity in neurons possessing unique genetic backgrounds of individual patients. While prior all-optical electrophysiology studies relied on genetically encoded voltage indicators, here, we demonstrate an alternative protocol using a synthetic voltage sensor and genetically encoded optogenetic actuator that generate robust and reproducible results. We demonstrate the functionality of this method by measuring spontaneous and evoked activity in three independent hiPSC-derived neuronal cell lines with distinct genetic backgrounds.