Memory Consolidation In Female Mice Research Articles

17β-estradiol activation of dorsal hippocampal TrkB is independent of increased mature BDNF expression and is required for enhanced memory consolidation in female mice

The potent estrogen 17β-estradiol (E2) is known to enhance hippocampal memory and plasticity, however the molecular mechanisms underlying these effects remain unclear. Brain derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB) are regulated by E2, but the potential mechanistic roles of neurotrophic signaling in E2-induced enhancement of memory are not well understood. Here, we examined the effects of hippocampal TrkB signaling on E2-induced enhancement of memory consolidation in the object placement and recognition tasks. Bilateral infusion of the TrkB antagonist ANA-12 into the dorsal hippocampus of ovariectomized female mice blocked E2-induced enhancement of memory consolidation, supporting a role for TrkB-mediated signaling in estrogenic regulation of memory. Although dorsal hippocampal E2 infusion increased levels of phospho-TrkB and mature BDNF (mBDNF) in the dorsal hippocampus within 4–6 h, E2-induced increases in hippocampal mBDNF expression were not required for hippocampal TrkB activation and were not inhibited by TrkB antagonism. Thus, E2 regulates TrkB signaling to facilitate memory consolidation in a manner independent of mBDNF expression. Together these results provide the first direct evidence that E2 modulation of hippocampal TrkB signaling is required for its beneficial effects on memory consolidation and provide additional characterization of the ways in which TrkB/BDNF signaling is regulated by E2 in the hippocampus.

Chemogenetic inactivation of the dorsal hippocampus and medial prefrontal cortex, individually and concurrently, impairs object recognition and spatial memory consolidation in female mice

The dorsal hippocampus (DH) and medial prefrontal cortex (mPFC) are brain regions essential for processing and storing episodic memory. In rodents, the DH has a well-established role in supporting the consolidation of episodic-like memory in tasks such as object recognition and object placement. However, the role of the mPFC in the consolidation of episodic-like memory tasks remains controversial. Therefore, the present study examined involvement of the DH and mPFC, alone and in combination, in object and spatial recognition memory consolidation in ovariectomized female mice. To this end, we utilized two types of inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to inactivate the DH alone, the mPFC alone, or both brain regions concurrently immediately after object training to assess the role of each region in the consolidation of object recognition and spatial memories. Our results using single and multiplexed DREADDS suggest that excitatory activity in the DH and mPFC, alone or in combination, is required for the successful consolidation of object recognition and spatial memories. Together, these studies provide critical insight into how the DH and mPFC work in concert to facilitate memory consolidation in female mice.

Post-training estrogen enhances spatial and object memory consolidation in female mice

The present study was designed to determine if post-training injections of a water-soluble form of 17β-estradiol could enhance spatial and object memory consolidation in young female mice. Young ovariectomized female mice were trained in Morris water maze and object recognition tasks, injected with 0.1, 0.2, or 0.4 mg/kg cyclodextrin-encapsulated 17β-estradiol or cyclodextrin-conjugated vehicle, and then re-tested after a delay. In the water maze, mice were trained in eight consecutive trials, injected, and memory for the platform location was re-tested after 24 h. All mice learned to find the platform on Day 1, but only mice receiving 0.2 mg/kg estradiol remembered the platform location on Day 2. In the object recognition task, mice were first presented with two identical objects, injected, and then presented with a familiar and novel object after a 24- or 48-h delay. For both delays, the 0.2 and 0.4 mg/kg doses enhanced memory for the familiar object. These data demonstrate that a 0.2 mg/kg dose of estradiol can enhance multiple types of memory consolidation in female mice, and suggest a narrower effective dose range for spatial memory than for object memory.