The neural circuits underlying memory change over prolonged periods after learning, in a process known as systems consolidation. Postlearning spontaneous reactivation of memory-related neural ensembles is thought to mediate this process, although a causal link has not been established. Here we test this hypothesis in mice by using optogenetics to selectively reactivate neural ensembles representing a contextual fear memory (sometimes referred to as engram neurons). High-frequency stimulation of these ensembles in the retrosplenial cortex 1 day after learning produced a recent memory with features normally observed in consolidated remote memories, including higher engagement of neocortical areas during retrieval, contextual generalization, and decreased hippocampal dependence. Moreover, this effect was only present if memory ensembles were reactivated during sleep or light anesthesia. These results provide direct support for postlearning memory ensemble reactivation as a mechanism of systems consolidation, and show that this process can be accelerated by ensemble reactivation in an unconscious state. engram | memory consolidation | retrosplenial cortex | fear conditioning | replay T he ability to encode and retrieve episodic memories requires coordinated activity in diverse brain areas, including the thalamus, neocortex, and areas of the medial-temporal lobe such as the hippocampus (HPC) (1-3). At the time of learning, synaptic plasticity is thought to occur in a subset of neurons that are activated during the experience and become part of the neural ensemble representing the specific memory, sometimes referred to as the memory engram (4). These changes occur rapidly with memory encoding, and are essential for the initial formation and maintenance of memory (5, 6). As time passes, memory ensembles throughout the brain are further stabilized and modified through a process known as systems memory consolidation, which is thought to be necessary for the maintenance, integration, and correct categorization of new information (7,8). This process is usually slow (months to years in humans and weeks to months in rodents) and changes the relative contribution of different brain areas for memory retrieval. Studies from both humans and rodents show that the hippocampus is preferentially engaged during learning and recent memory retrieval, whereas neocortical areas are more active when a remote memory is retrieved (9-11). In addition, some neocortical areas involved in remote memory are not necessary for recent memory retrieval (9, 12), whereas the hippocampus is generally dispensable for remote memory retrieval (13-16), although some recent studies have challenged this idea (12,17). Interestingly, these broad changes at the neural circuit level are often accompanied by changes in the quality of memory. For example, humans tend to lose details of episodic memories as time passes (18), and rodents are unable to discriminate between two different contexts in a remote retrieval trial in the context fear conditioning (CFC) paradi...

BackgroundOlfaction is a fundamental sense through which most animals perceive the external world. The olfactory system detects odors via specialized sensory organs such as the main olfactory epithelium and the vomeronasal organ. Sensory neurons in these organs use G-protein coupled receptors to detect chemosensory stimuli. The odorant receptor (OR) family is expressed in sensory neurons of the main olfactory epithelium, while the adult vomeronasal organ is thought to express other types of receptors.ResultsHere, we describe Olfr692, a member of the OR gene family identified by next-generation RNA sequencing, which is highly upregulated and non-canonically expressed in the vomeronasal organ. We show that neurons expressing this gene are activated by odors emanating from pups. Surprisingly, activity in Olfr692-positive cells is sexually dimorphic, being very low in females. Our results also show that juvenile odors activate a large number of Olfr692 vomeronasal neurons in virgin males, which is correlated with the display of infanticide behavior. . In contrast, activity substantially decreases in parenting males (fathers), where infanticidal aggressive behavior is not frequently observed.ConclusionsOur results describe, for the first time, a sensory neural population with a specific molecular identity involved in the detection of pup odors. Moreover, it is one of the first reports of a group of sensory neurons the activity of which is sexually dimorphic and depends on social status. Our data suggest that the Olfr692 population is involved in mediating pup-oriented behaviors in mice.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-016-0234-9) contains supplementary material, which is available to authorized users.