Summary Theories of associative memory suggest that successful memory storage and recall depends on a balance between two complementary processes: pattern separation (to minimize interference) and pattern completion (to retrieve a memory when presented with partial or degraded input cues). Putative attractor circuitry in the hippocampal CA3 region is thought to be the final arbiter between these two processes. Here we present the first direct, quantitative evidence that CA3 produces an output pattern closer to the originally stored representation than its degraded input patterns from the dentate gyrus (DG). We simultaneously recorded activity from CA3 and DG of behaving rats when local and global reference frames were placed in conflict. CA3 showed a coherent population response to the conflict (pattern completion), even though its DG inputs were severely disrupted (pattern separation). The results thus confirm the hallmark predictions of a longstanding computational model of hippocampal memory processing.

The hippocampus receives its major cortical input from the medial entorhinal cortex (MEC) and the lateral entorhinal cortex (LEC). It is commonly believed that the MEC provides spatial input to the hippocampus, whereas the LEC provides non-spatial input. We review new data which suggest that this simple dichotomy between ‘where’ versus ‘what’ needs revision. We propose a refinement of this model, which is more complex than the simple spatial–non-spatial dichotomy. MEC is proposed to be involved in path integration computations based on a global frame of reference, primarily using internally generated, self-motion cues and external input about environmental boundaries and scenes; it provides the hippocampus with a coordinate system that underlies the spatial context of an experience. LEC is proposed to process information about individual items and locations based on a local frame of reference, primarily using external sensory input; it provides the hippocampus with information about the content of an experience.

Classic computational theories of the mnemonic functions of the hippocampus ascribe the processes of pattern separation to the dentate gyrus (DG) and pattern completion to the CA3 region. Until the last decade, the large majority of single-unit studies of the hippocampus in behaving animals were from the CA1 region. The lack of data from the DG, CA3, and the entorhinal inputs to the hippocampus severely hampered the ability to test these theories with neurophysiological techniques. The past ten years have seen a major increase in the recordings from the CA3 region and the medial entorhinal cortex (MEC), with an increasing (but still limited) number of experiments from the lateral entorhinal cortex (LEC) and DG. This paper reviews a series of studies in a local-global cue mismatch (double-rotation) experiment in which recordings were made from cells in the anterior thalamus, MEC, LEC, DG, CA3, and CA1 regions. Compared to the standard cue environment, the change in the DG representation of the cue-mismatch environment was greater than the changes in its entorhinal inputs, providing support for the theory of pattern separation in the DG. In contrast, the change in the CA3 representation of the cue-mismatch environment was less than the changes in its entorhinal and DG inputs, providing support for a pattern completion/error correction function of CA3. The results are interpreted in terms of continuous attractor network models of the hippocampus and the relationship of these models to pattern separation and pattern completion theories. Whereas DG may perform an automatic pattern separation function, the attractor dynamics of CA3 allow it to perform a pattern separation or pattern completion function, depending on the nature of its inputs and the relative strength of the internal attractor dynamics.

During courtship males attract females with elaborate behaviors. In mice, these displays include ultrasonic vocalizations. Ultrasonic courtship vocalizations were previously attributed to the courting male, despite evidence that both sexes produce virtually indistinguishable vocalizations. Because of this similarity, and the difficulty of assigning vocalizations to individuals, the vocal contribution of each individual during courtship is unknown. To address this question, we developed a microphone array system to localize vocalizations from socially interacting, individual adult mice. With this system, we show that female mice vocally interact with males during courtship. Males and females jointly increased their vocalization rates during chases. Furthermore, a female's participation in these vocal interactions may function as a signal that indicates a state of increased receptivity. Our results reveal a novel form of vocal communication during mouse courtship, and lay the groundwork for a mechanistic dissection of communication during social behavior.DOI: http://dx.doi.org/10.7554/eLife.06203.001

The dentate gyrus (DG) occupies a key position in information flow through the hippocampus. Its principal cell, the granule cell, has spatially selective place fields. However, the behavioral correlates of cells located in the hilus of the rat dentate gyrus are unknown. We report here that cells below the granule layer show spatially selective firing that consists of multiple subfields. Other cells recorded from the DG had single place fields. Compared to cells with multiple fields, cells with single fields fired at lower rates during sleep; were less bursty; and were more likely to be recorded simultaneously with large populations of neurons that were active during sleep and silent during behavior. We propose that cells with single fields are likely to be mature granule cells that use sparse encoding to potentially disambiguate input patterns. Furthermore, we hypothesize that cells with multiple fields might be cells of the hilus or newborn granule cells. These data are the first demonstration, based on physiological criteria, that single-field and multiple-field cells constitute at least two distinct cell classes in the DG. Because of the heterogeneity of firing correlates and cell types in the DG, understanding which cell types correspond to which firing patterns, and how these correlates change with behavioral state and between different environments, are critical questions for testing longstanding computational theories that the DG performs a pattern separation function using a very sparse coding strategy.

Manipulation of spatial reference frames is a common experimental tool to investigate the nature of hippocampal information coding and to investigate high-order processes, such as cognitive coordination. However, it is unknown how the hippocampus afferents represent the local and global reference frames of an environment. To address these issues, single units were recorded in freely moving rats with multi-tetrode arrays targeting the superficial layers of the lateral entorhinal cortex (LEC) and medial entorhinal cortex (MEC), the two primary cortical inputs to the hippocampus. Rats ran clockwise laps around a circular track partitioned into quadrants covered by different textures (the local reference frame). The track was centered in a circular environment with distinct landmarks on the walls (the global reference frame). Here we demonstrate a novel dissociation between MEC and LEC in that the global frame controlled the MEC representation and the local frame controlled the LEC representation when the reference frames were rotated in equal, but opposite, directions. Consideration of the functional anatomy of the hippocampal circuit and popular models of attractor dynamics in CA3 suggests a mechanistic explanation of previous data showing a dissociation between the CA3 and CA1 regions in their responses to this local–global conflict. Furthermore, these results are consistent with a model of the LEC providing the hippocampus with the external sensory content of an experience and the MEC providing the spatial context, which combine to form conjunctive codes in the hippocampus that form the basis of episodic memory.

Communication plays an integral role in human social dynamics and is impaired in several neurodevelopmental disorders. Mice are used to study the neurobiology of social behavior; however, the extent to which mouse vocalizations influence social dynamics has remained elusive because it is difficult to identify the vocalizing animal among mice involved in a group interaction. By tracking the ultrasonic vocal behavior of individual mice and using an algorithm developed to group phonically similar signals, we show that distinct patterns of vocalization emerge as male mice perform specific social actions. Mice dominating other mice were more likely to emit different vocal signals than mice avoiding social interactions. Furthermore, we show that the patterns of vocal expression influence the behavior of the socially-engaged partner but no other animals in the cage. These findings clarify the function of mouse communication by revealing a communicative ultrasonic signaling repertoire.

Ultrasonic vocalizations (USVs) are believed to play a critical role in mouse communication. Although mice produce USVs in multiple contexts, signals emitted in reproductive contexts are typically attributed solely to the male mouse. Only recently has evidence emerged showing that female mice are also vocally active during mixed-sex interactions. Therefore, this study aimed to systematically quantify and compare vocalizations emitted by female and male mice as the animals freely interacted. Using an eight-channel microphone array to determine which mouse emitted specific vocalizations during unrestrained social interaction, we recorded 13 mixed-sex pairs of mice. We report here that females vocalized significantly less often than males during dyadic interactions, with females accounting for approximately one sixth of all emitted signals. Moreover, the acoustic features of female and male signals differed. We found that the bandwidths (i.e., the range of frequencies that a signal spanned) of female-emitted signals were smaller than signals produced by males. When examining how the frequency of each signal changed over time, the slopes of male-emitted signals decreased more rapidly than female signals. Further, we revealed notable differences between male and female vocal signals when the animals were performing the same behaviors. Our study provides evidence that a female mouse does in fact vocalize during interactions with a male and that the acoustic features of female and male vocalizations differ during specific behavioral contexts.