Lara M. Rangel

Temporally selective contextual encoding in the dentate gyrus of the hippocampus

A recent model of the hippocampus predicts that the unique properties of the dentate gyrus allow for temporal separation of events. This temporal separation is accomplished in part through the continual generation of new neurons, which, due to a transient window of hyperexcitability, could allow for preferential encoding of information present during their development. Here we obtain in vivo electrophysiological recordings and identify a cell population exhibiting activity that is selective to single contexts when rats experience a long temporal separation between context exposures during training. This selectivity is attenuated as the temporal separation between context exposures is shortened and is further attenuated when neurogenesis is reduced. Our data reveal the existence of a temporal orthogonalizing neuronal code within the dentate gyrus, a hallmark feature of episodic memory.

A Hypothesis for Temporal Coding of Young and Mature Granule Cells.

While it has been hypothesized that adult neurogenesis (NG) plays a role in the encoding of temporal information at long time-scales, the temporal relationship of immature cells to the highly rhythmic network activity of the hippocampus has been largely unexplored. Here, we present a theory for how the activity of immature adult-born granule cells relates to hippocampal oscillations. Our hypothesis is that theta rhythmic (5–10 Hz) excitatory and inhibitory inputs into the hippocampus could differentially affect young and mature granule cells due to differences in intrinsic physiology and synaptic inhibition between the two cell populations. Consequently, immature cell activity may occur at broader ranges of theta phase than the activity of their mature counterparts. We describe how this differential influence on young and mature granule cells could separate the activity of differently aged neurons in a temporal coding regime. Notably, this process could have considerable implications on how the downstream CA3 region interprets the information conveyed by young and mature granule cells. To begin to investigate the phasic behavior of granule cells, we analyzed in vivo recordings of the rat dentate gyrus (DG), observing that the temporal behavior of granule cells with respect to the theta rhythm is different between rats with normal and impaired levels of NG. Specifically, in control animals, granule cells exhibit both strong and weak coupling to the phase of the theta rhythm. In contrast, the distribution of phase relationships in NG-impaired rats is shifted such that they are significantly stronger. These preliminary data support our hypothesis that immature neurons could distinctly affect the temporal dynamics of hippocampal encoding.

Transient optogenetic inactivation of the medial entorhinal cortex biases the active population of hippocampal neurons

The mechanisms that enable the hippocampal network to express the appropriate spatial representation for a particular circumstance are not well understood. Previous studies suggest that the medial entorhinal cortex (MEC) may have a role in reproducibly selecting the hippocampal representation of an environment. To examine how ongoing MEC activity is continually integrated by the hippocampus, we performed transient unilateral optogenetic inactivations of the MEC while simultaneously recording place cell activity in CA1. Inactivation of the MEC caused a partial remapping in the CA1 population without diminishing the degree of spatial tuning across the active cell assembly. These changes remained stable irrespective of intermittent disruption of MEC input, indicating that while MEC input is integrated over long time scales to bias the active population, there are mechanisms for stabilizing the population of active neurons independent of the MEC. We find that MEC inputs to the hippocampus shape its ongoing activity by biasing the participation of the neurons in the active network, thereby influencing how the hippocampus selectively represents information.

Young adult born neurons enhance hippocampal dependent performance via influences on bilateral networks

Adult neurogenesis supports performance in many hippocampal dependent tasks. Considering the small number of adult-born neurons generated at any given time, it is surprising that this sparse population of cells can substantially influence behavior. Recent studies have demonstrated that heightened excitability and plasticity may be critical for the contribution of young adult-born cells for certain tasks. What is not well understood is how these unique biophysical and synaptic properties may translate to networks that support behavioral function. Here we employed a location discrimination task in mice while using optogenetics to transiently silence adult-born neurons at different ages. We discovered that adult-born neurons promote location discrimination during early stages of development but only if they undergo maturation during task acquisition. Silencing of young adult-born neurons also produced changes extending to the contralateral hippocampus, detectable by both electrophysiology and fMRI measurements, suggesting young neurons may modulate location discrimination through influences on bilateral hippocampal networks. DOI: http://dx.doi.org/10.7554/eLife.22429.001

Theta and beta oscillatory dynamics in the dentate gyrus reveal a shift in network processing state during cue encounters

The hippocampus is an important structure for learning and memory processes, and has strong rhythmic activity. Although a large amount of research has been dedicated toward understanding the rhythmic activity in the hippocampus during exploratory behaviors, specifically in the theta (5–10 Hz) frequency range, few studies have examined the temporal interplay of theta and other frequencies during the presentation of meaningful cues. We obtained in vivo electrophysiological recordings of local field potentials (LFP) in the dentate gyrus (DG) of the hippocampus as rats performed three different associative learning tasks. In each task, cue presentations elicited pronounced decrements in theta amplitude in conjunction with increases in beta (15–30 Hz) amplitude. These changes were often transient but were sustained from the onset of cue encounters until the occurrence of a reward outcome. This oscillatory profile shifted in time to precede cue encounters over the course of the session, and was not present during similar behaviors in the absence of task relevant stimuli. The observed decreases in theta amplitude and increases in beta amplitude in the DG may thus reflect a shift in processing state that occurs when encountering meaningful cues.

Rhythmic coordination of hippocampal neurons during associative memory processing

Hippocampal oscillations are dynamic, with unique oscillatory frequencies present during different behavioral states. To examine the extent to which these oscillations reflect neuron engagement in distinct local circuit processes that are important for memory, we recorded single cell and local field potential activity from the CA1 region of the hippocampus as rats performed a context-guided odor-reward association task. We found that theta (4–12 Hz), beta (15–35 Hz), low gamma (35–55 Hz), and high gamma (65–90 Hz) frequencies exhibited dynamic amplitude profiles as rats sampled odor cues. Interneurons and principal cells exhibited unique engagement in each of the four rhythmic circuits in a manner that related to successful performance of the task. Moreover, principal cells coherent to each rhythm differentially represented task dimensions. These results demonstrate that distinct processing states arise from the engagement of rhythmically identifiable circuits, which have unique roles in organizing task-relevant processing in the hippocampus. DOI: http://dx.doi.org/10.7554/eLife.09849.001

What's new is older

Distinct populations of active cells in the dentate gyrus of the hippocampus may facilitate the unique encoding of changes in the environment.

Brain rhythms: towards a coherent picture of ensemble development in learning.

A recent study suggests that coherence of 20-40 Hz brain oscillations in the hippocampus and upstream lateral entorhinal cortex may support encoding of task-relevant information during associative learning. Coordination of local hippocampal circuits in this frequency range could be important for encoding new information.

Neurophysiological signatures of temporal coordination between retrosplenial cortex and the hippocampal formation.

Retrosplenial cortex (RSC) is heavily interconnected with a multitude of cortical regions and is directly connected with the hippocampal formation. As such, it is a likely coordinator of information transfer between the hippocampus (HPC) and cortex in the service of spatial cognition and episodic memory. The current work examined three potential temporal frameworks for retrosplenial–hippocampal communication, namely, theta frequency oscillations (6–12 Hz), sharp-wave/ripple events, and repeating, theta phase-locked shifts from low (30–65 Hz) to high (120–160 Hz) gamma frequency oscillations. From simultaneous recordings of single units and local field potentials (LFPs) in RSC and HPC, we report the presence of prominent theta, low-gamma, and high-gamma oscillations in the retrosplenial LFP. Retrosplenial and hippocampal theta rhythms were strongly coherent and subgroups of retrosplenial neurons exhibited either spiking at theta frequencies and/or spike-phase-locking to theta. Retrosplenial neurons were also phase-locked to local low- and high-gamma rhythms, and power in these frequency bands was coupled in a sequential fashion to specific phases of hippocampal and retrosplenial theta rhythms. Coordinated activity between the two regions also occurred during hippocampal sharp-wave/ripple events, where retrosplenial neuron populations were modulated in their spiking and retrosplenial LFPs exhibited sharp-wave-like events that co-occurred with those observed in HPC. These results identify several temporal windows of synchronization between RSC and HPC that may mediate cortico-hippocampal processes related to learning, memory, and spatial representation.

Space, Time, and the Hippocampus

Kesner’s attribute model of memory endows the hippocampus with the ability to code both time and space. These two parameters are intertwined in their very essence and lend structure to the ongoing autobiographical record of an organism. Kesner’s addition of time and temporal processing to the notion that the hippocampus supports a spatial cognitive map, fused hippocampal theory into a coherent framework for human and non-human animals. The mechanism by which the hippocampus and its associated circuitry supports memory for time is a fertile area of research that was seeded by Kesner and his contemporaries. The inherent physiological properties of the hippocampus support Kesner’s original hypothesis, emphasizing that temporal and spatial inputs converge in the hippocampus. The temporal scale of this convergence is evident from patterns of neuronal firing to enduring memories.