Coordinated memory processing between the dorsal and ventral hippocampus and the nucleus accumbens

The brain’s ability to associate experiences with subsequent rewards is fundamental to learning and memory and critical for animal survival. The neural substrates of this process are only partially understood, but are thought to rely on interactions between the hippocampus and nucleus accumbens (NAc). In particular, hippocampal input to the NAc is thought to be crucial for learning and remembering links between spatial information and reward. Hippocampal projections to the NAc arise from both the ventral hippocampus (vH) and the dorsal hippocampus (dH), and studies using optogenetic interventions have demonstrated that either vH or dH input to the NAc can support behaviors dependent on spatial-reward associations. It remains unclear, however, whether dH, vH, or both coordinate memory processing of spatial-reward information in the hippocampal-NAc circuit under normal conditions. Moreover, as dH and vH are thought to encode different aspects of an experience, whether the hippocampus can compartmentalize different types of information to circuits in the NAc is unknown. Times of memory reactivation within and outside the hippocampus are marked by hippocampal sharp-wave ripples (SWRs), discrete events which facilitate investigation of inter-regional information processing. It is unknown whether dH and vH SWRs act in concert or separately to engage NAc neuronal networks, and whether either dH or vH SWRs are preferentially linked to spatial-reward representations. To address these questions, we performed simultaneous extracellular recordings using multi-tetrode arrays in the dH, vH, and NAc of rats learning and performing an appetitive spatial task and during sleep. We report that dH and vH SWRs occur asynchronously, and that individual NAc neurons activated during SWRs from one subdivision of the hippocampus are typically suppressed or unmodulated during SWRs from the other. Furthermore, NAc neurons activated during dH versus vH SWRs show markedly different task-related firing patterns, with NAc representations related to space and reward selectively activated during dH SWRs and not vH SWRs. Our findings reveal that dorsal and ventral hippocampal interactions with the NAc are temporally and anatomically separable at times of memory processing. This work suggests that the dH-NAc and vH-NAc networks provide distinct information channels, with the dH-NAc channel dedicated to linking spatial paths with reward and reward-seeking actions. More broadly, these circuit dynamics could provide a potential neural substrate for the brain’s ability to compartmentalize aspects of experience in memory

Coordinated memory processing between the dorsal and ventral hippocampus and the nucleus accumbens

The brain’s ability to associate experiences with subsequent rewards is fundamental to learning and memory and critical for animal survival. The neural substrates of this process are only partially understood, but are thought to rely on interactions between the hippocampus and nucleus accumbens (NAc). In particular, hippocampal input to the NAc is thought to be crucial for learning and remembering links between spatial information and reward. Hippocampal projections to the NAc arise from both the ventral hippocampus (vH) and the dorsal hippocampus (dH), and studies using optogenetic interventions have demonstrated that either vH or dH input to the NAc can support behaviors dependent on spatial-reward associations. It remains unclear, however, whether dH, vH, or both coordinate memory processing of spatial-reward information in the hippocampal-NAc circuit under normal conditions. Moreover, as dH and vH are thought to encode different aspects of an experience, whether the hippocampus can compartmentalize different types of information to circuits in the NAc is unknown. Times of memory reactivation within and outside the hippocampus are marked by hippocampal sharp-wave ripples (SWRs), discrete events which facilitate investigation of inter-regional information processing. It is unknown whether dH and vH SWRs act in concert or separately to engage NAc neuronal networks, and whether either dH or vH SWRs are preferentially linked to spatial-reward representations. To address these questions, we performed simultaneous extracellular recordings using multi-tetrode arrays in the dH, vH, and NAc of rats learning and performing an appetitive spatial task and during sleep. We report that dH and vH SWRs occur asynchronously, and that individual NAc neurons activated during SWRs from one subdivision of the hippocampus are typically suppressed or unmodulated during SWRs from the other. Furthermore, NAc neurons activated during dH versus vH SWRs show markedly different task-related firing patterns, with NAc representations related to space and reward selectively activated during dH SWRs and not vH SWRs. Our findings reveal that dorsal and ventral hippocampal interactions with the NAc are temporally and anatomically separable at times of memory processing. This work suggests that the dH-NAc and vH-NAc networks provide distinct information channels, with the dH-NAc channel dedicated to linking spatial paths with reward and reward-seeking actions. More broadly, these circuit dynamics could provide a potential neural substrate for the brain’s ability to compartmentalize aspects of experience in memory

Dorsal and Ventral Hippocampal Sharp-Wave Ripples Activate Distinct Nucleus Accumbens Networks.

Memories of positive experiences link places, events, and reward outcomes. These memories recruit interactions between the hippocampus and nucleus accumbens (NAc). Both dorsal and ventral hippocampus (dH and vH) project to the NAc, but it remains unknown whether dH and vH act in concert or separately to engage NAc representations related to space and reward. We recorded simultaneously from the dH, vH, and NAc of rats during an appetitive spatial task and focused on hippocampal sharp-wave ripples (SWRs) to identify times of memory reactivation across brain regions. Here, we show that dH and vH awake SWRs occur asynchronously and activate distinct and opposing patterns of NAc spiking. Only NAc neurons activated during dH SWRs were tuned to task- and reward-related information. These temporally and anatomically separable hippocampal-NAc interactions point to distinct channels of mnemonic processing in the NAc, with the dH-NAc channel specialized for spatial task and reward information. VIDEO ABSTRACT

Neural Activity Patterns Underlying Spatial Coding in the Hippocampus

The hippocampus is well known as a central site for memory processing-critical for storing and later retrieving the experiences events of daily life so they can be used to shape future behavior. Much of what we know about the physiology underlying hippocampal function comes from spatial navigation studies in rodents, which have allowed great strides in understanding how the hippocampus represents experience at the cellular level. However, it remains a challenge to reconcile our knowledge of spatial encoding in the hippocampus with its demonstrated role in memory-dependent tasks in both humans and other animals. Moreover, our understanding of how networks of neurons coordinate their activity within and across hippocampal subregions to enable the encoding, consolidation, and retrieval of memories is incomplete. In this chapter, we explore how information may be represented at the cellular level and processed via coordinated patterns of activity throughout the subregions of the hippocampal network

Neural Activity Patterns Underlying Spatial Coding in the Hippocampus.

The hippocampus is well known as a central site for memory processing-critical for storing and later retrieving the experiences events of daily life so they can be used to shape future behavior. Much of what we know about the physiology underlying hippocampal function comes from spatial navigation studies in rodents, which have allowed great strides in understanding how the hippocampus represents experience at the cellular level. However, it remains a challenge to reconcile our knowledge of spatial encoding in the hippocampus with its demonstrated role in memory-dependent tasks in both humans and other animals. Moreover, our understanding of how networks of neurons coordinate their activity within and across hippocampal subregions to enable the encoding, consolidation, and retrieval of memories is incomplete. In this chapter, we explore how information may be represented at the cellular level and processed via coordinated patterns of activity throughout the subregions of the hippocampal network

A Variable Clock Underlies Internally Generated Hippocampal Sequences.

Humans have the ability to store and retrieve memories with various degrees of specificity, and recent advances in reinforcement learning have identified benefits to learning when past experience is represented at different levels of temporal abstraction. How this flexibility might be implemented in the brain remains unclear. We analyzed the temporal organization of male rat hippocampal population spiking to identify potential substrates for temporally flexible representations. We examined activity both during locomotion and during memory-associated population events known as sharp-wave ripples (SWRs). We found that spiking during SWRs is rhythmically organized with higher event-to-event variability than spiking during locomotion-associated population events. Decoding analyses using clusterless methods further indicate that a similar spatial experience can be replayed in multiple SWRs, each time with a different rhythmic structure whose periodicity is sampled from a log-normal distribution. This variability increases with experience despite the decline in SWR rates that occurs as environments become more familiar. We hypothesize that the variability in temporal organization of hippocampal spiking provides a mechanism for storing experiences with various degrees of specificity.SIGNIFICANCE STATEMENT One of the most remarkable properties of memory is its flexibility: the brain can retrieve stored representations at varying levels of detail where, for example, we can begin with a memory of an entire extended event and then zoom in on a particular episode. The neural mechanisms that support this flexibility are not understood. Here we show that hippocampal sharp-wave ripples, which mark the times of memory replay and are important for memory storage, have a highly variable temporal structure that is well suited to support the storage of memories at different levels of detail

Hippocampal replay of experience at real-world speeds.

Representations related to past experiences play a critical role in memory and decision-making processes. The rat hippocampus expresses these types of representations during sharp-wave ripple (SWR) events, and previous work identified a minority of SWRs that contain 'replay' of spatial trajectories at ∼20x the movement speed of the animal. Efforts to understand replay typically make multiple assumptions about which events to examine and what sorts of representations constitute replay. We therefore lack a clear understanding of both the prevalence and the range of representational dynamics associated with replay. Here, we develop a state space model that uses a combination of movement dynamics of different speeds to capture the spatial content and time evolution of replay during SWRs. Using this model, we find that the large majority of replay events contain spatially coherent, interpretable content. Furthermore, many events progress at real-world, rather than accelerated, movement speeds, consistent with actual experiences