Social memory in female mice is rapidly modulated by 17β-estradiol through ERK and Akt modulation of synapse formation
BackgroundSocial memory is essential to the functioning of a social animal within a group. Estrogens can affect social memory too quickly for classical genomic mechanisms. Previously, 17{beta}-estradiol (E2) rapidly facilitated short-term social memory and increased nascent synapse formation, these synapses being potentiated following neuronal activity. However, what mechanisms underlie and co-ordinate the rapid facilitation of social memory and synaptogenesis are unclear. Here, the necessity of extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K) signaling for rapid facilitation of short-term social memory and synaptogenesis was tested. MethodsMice performed a short-term social memory task or were used as task-naive controls. ERK and PI3K pathway inhibitors were infused intra-dorsal hippocampally 5 minutes before E2 infusion. Forty minutes following intrahippocampal E2 or vehicle administration, tissues were collected for quantification of glutamatergic synapse number in the CA1. ResultsDorsal hippocampal E2 rapid facilitation of short-term social memory depended upon ERK and PI3K pathways. E2 increased glutamatergic synapse number (GluA1/bassoon colocalization) in task-performing mice but decreased synapse number in task-naive mice. Critically, ERK signaling was required for synapse formation/elimination in task-performing and task-naive mice, whereas PI3K inhibition blocked synapse formation only in task-performing mice. ConclusionsWhilst ERK and PI3K are both required for E2 facilitation of short-term social memory and synapse formation, only ERK is required for synapse elimination. This demonstrates previously unknown, bidirectional, rapid actions of E2 on brain and behaviour and underscores the importance of estrogen signaling in the brain to social behaviour.