New perspectives on sex differences in learning and memory

Although male rodents are thought to exhibit better spatial and fear memories compared with females, the sexes often respond differently to learning stimuli, resulting in mischaracterization of female memory abilities. Responses to learning stimuli are influenced by sex steroid hormones and sex. High hormone levels are associated with place strategies in spatial tasks. In fear tasks, males use passive strategies, whereas females use passive and active strategies. The sexes differ in neural mechanisms underlying memory formation, as indicated by basal, learning-induced, and hormone-driven brain region- and cell type-specific sex differences in cellular activity and morphology. Better understanding of how sex differences in neural function contribute to sex differences in memory is vital and will lead to next-generation therapies for memory disorders in both sexes. the most potent and ubiquitous estrogen synthesized before menopause and outside of pregnancy. darting or flight-like responses to fearful stimuli. biosynthetic enzyme responsible for converting androgens into estrogens. hub of the fear brain circuit where fear signals are integrated and processed as a whole experience and consolidated into one memory. navigation strategy in which specific objects in the environment are used as landmarks to locate a goal. knobby protuberances on excitatory dendrites that constitute the most common postsynaptic localization for excitatory synapses. dorsal portion of the hippocampus with a well-established role in mediating the formation of spatial, contextual, and recognition memories. process by which fear responses, such as freezing or darting, are elicited by repeatedly pairing an aversive stimulus, such as a footshock, with a neutral stimulus (e.g., tone) or context. process by which the fear response is reduced over time through multiple re-exposures to a fear-associated stimulus or context without concurrently presenting footshocks. associating a fearful stimulus with multiple other stimuli, such that fear learning in one context elicits fear behaviors in a unique, yet similar, context. genetically XX or XY mice in which ovaries or testes can be expressed by regulating the testes-determining gene. genes that are activated rapidly after cellular stimulation, often acting as transcription factors for other genes that promote neuronal plasticity. strong excitatory stimulation triggers postsynaptic signaling that produces a prolonged increase in excitatory postsynaptic physiological responses. anterior midline portion of the prefrontal cortex that mediates working and long-term memory in numerous domains (e.g., spatial, recognition, or fear), as well as judgement and decision-making processes. process of transferring memory from short-term to long-term storage. Cellular activity, inter- and intraregion connectivity, protein synthesis and activation, and dendritic remodeling are all associated with consolidation. freezing or stationary responses to fearful stimuli. spatial navigation strategy in which geometric and relational extra-maze cues, such as environment shape or spatial relations among environmental cues, are used to locate a goal. form of long-term memory in which previously learned information that does not change over time guides future behavior. very long-term memory system in which information learned long before recall guides future behavior. part of the 2014 NIH mandate requiring funded research to consider sex as a biological variable in grant proposals. Proposals need not include both sexes but must consider how sex may affect experimental variables. changes in cellular activity, signaling cascades, and cellular morphology in neurons that make postsynaptic cells respond more effectively to future presentations of the same stimulus; often considered the biological manifestation of learning. form of short-term memory in which newly learned information guides future behavior.