Foxg1 promotes neuron allocation to engrams and facilitates fear memorization

ABSTRACT In addition to orchestrate telencephalic development, the transcription factor Foxg1 is involved in mutual positive feedback with neuronal activity. Based on that, we hypothesized an involvement of it in learning and engram dynamics. We observed that its sparse and mild neuronal upregulation improved learning abilities as evaluated by a CFC assay. This effect was specifically pronounced upon early memory retrieval and disappeared when Foxg1-GOF neurons were silenced by a Gi DREADD effector. A prevailing positive relationship was detectable between Foxg1 expression level and the probability of a neuron getting recruited into training and recall engrams, in structures involved in both short- and long-term memory formation. Moreover, Foxg1 upregulation elicited a generalized shrinkage of engrams and increased the fraction of late recall engram cells already active at the time of training. Together, these findings establish Foxg1 as a key effector linking neuronal excitability to engram allocation and memory recall.