Social memory in female mice is rapidly modulated by 17ß-estradiol through ERK and Akt modulation of synapse formation.

Social 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, 17ß-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 coordinate 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. Mice performed a short-term social memory task or were used as task-naïve controls. ERK and PI3K pathway inhibitors were infused intradorsal hippocampally 5 min before E2 infusion. Forty minutes following intrahippocampal E2 or vehicle administration, tissues were collected for quantification of glutamatergic synapse number in the CA1. Dorsal hippocampal E2 rapid facilitation of short-term social memory depended upon ERK and PI3K pathways. E2 increased glutamatergic synapse number (bassoon puncta positive for GluA1) in task-performing mice but decreased synapse number in task-naïve mice. Critically, ERK signaling was required for synapse formation/elimination in task-performing and task-naïve mice, whereas PI3K inhibition blocked synapse formation only in task-performing mice. While 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 behavior and underscores the importance of estrogen signaling in the brain to social behavior.

Probabilistic retro-cues do not determine state in visual working memory.

The effective use of our capacity-limited visual working memory (VWM) requires mechanisms that govern how it represents information. Validly cueing an item in VWM after encoding, for instance, enhances memory performance for that item and biases its state in VWM, bringing its representation to an active state such that attentional selection is biased towards perceptually similar inputs. Critically, when the retro-cue is less than 100% valid (i.e., probabilistic rather than deterministic), the effect of the cue on memory performance varies. Here we investigated whether deterministic and probabilistic retro-cues also differ in their influence over item state in VWM. Participants encoded two colored squares, and a retro-cue indicated which item was most likely to be probed in a subsequent memory test. Across blocks, we manipulated cue validity to be deterministic (100% valid) or probabilistic (70% valid). On a subset of trials, no memory probe was presented and the trial ended with a visual search task in which a colored distractor -matching the cued memory item, the non-cued item, or neither - was presented. Predictably, in the deterministic condition, the presence of a singleton distractor matching the cued item reliably slowed reaction times during visual search. In the probabilistic condition, however, there were no differences in reaction times when the singleton matched the cued item or the non-cued item, despite a reliable benefit to memory performance on valid memory trials. We suggest that, while probabilistic retro-cues improve memory of the cued item, they are not sufficient to bias its state in VWM.