Memory-guided Behavior Research Articles

The anatomy and function of the postrhinal cortex.

The parahippocampal cortex (PHC) in the primate brain is implicated in the medial temporal lobe (MTL) memory network for spatial and episodic memory, but the precise function of this region remains unclear. Importantly, the rodent postrhinal cortex (POR) provides a structural and connectional homolog to the primate PHC. This homology permits the use of the powerful tools available in rodent models to better understand the function of the PHC in the human and nonhuman primate brains. Although many articles have compared and dissociated the function of the rodent POR from other areas in the MTL implicated in learning, memory, and memory-guided behavior, there are no in-depth reviews, particularly covering the last two decades of research. Nor has there been a review of the literature on the potential role of the POR in attention. Here, we review the anatomical and functional connectivity of the POR in rats, examine the evidence for proposed behavioral functions of this region, and suggest a model that accounts for the array of observations. We propose that the rodent POR binds nonspatial information and spatial information to represent the current local physical environment or context, including the geometry of the space and the spatial layout of objects and features in the environment. The POR also automatically monitors the environment for changes and updates representations when changes occur. These representations of context are available to be used by multiple brain regions, including prefrontal, posterior cortical, and hippocampal areas, for context-guided behavior, associative learning, and episodic memory. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Hippocampus-Prefrontal Coupling Regulates Recognition Memory for Novelty Discrimination.

Recognition memory provides the ability to distinguish familiar from novel objects and places, and is important for recording and updating events to guide appropriate behavior. The hippocampus (HPC) and medial prefrontal cortex (mPFC) have both been implicated in recognition memory, but the nature of HPC-mPFC interactions, and its impact on local circuits in mediating this process is not known. Here we show that novelty discrimination is accompanied with higher theta activity (4-10 Hz) and increased c-Fos expression in both these regions. Moreover, theta oscillations were highly coupled between the HPC and mPFC during recognition memory retrieval for novelty discrimination, with the HPC leading the mPFC, but not during initial learning. Principal neurons and interneurons in the mPFC responded more strongly during recognition memory retrieval compared with learning. Optogenetic silencing of HPC input to the mPFC disrupted coupled theta activity between these two structures, as well as the animals' (male Sprague Dawley rats) ability to differentiate novel from familiar objects. These results reveal a key role of monosynaptic connections between the HPC and mPFC in novelty discrimination via theta coupling and identify neural populations that underlie this recognition memory-guided behavior.SIGNIFICANCE STATEMENT Many memory processes are highly dependent on the interregional communication between the HPC and mPFC via neural oscillations. However, how these two brain regions coordinate their oscillatory activity to engage local neural populations to mediate recognition memory for novelty discrimination is poorly understood. This study revealed that the HPC and mPFC theta oscillations and their temporal coupling is correlated with recognition memory-guided behavior. During novel object recognition, the HPC drives mPFC interneurons to effectively reduce the activity of principal neurons. This study provides the first evidence for the requirement of the HPC-mPFC pathway to mediate recognition memory for novelty discrimination and describes a mechanism for how this memory is regulated.

Identifying brain regions supporting amygdalar functionality: Application of a novel graph theory technique

Effective amygdalar functionality depends on the concerted activity of a complex network of regions. Thus, the role of the amygdala cannot be fully understood without identifying the set of brain structures that allow the processes performed by the amygdala to emerge. However, this identification has yet to occur, hampering our ability to understand both normative and pathological processes that rely on the amygdala. We developed and applied novel graph theory methods to diffusion-based anatomical networks in a large sample (n = 1,052, 54.28% female, mean age=28.75) to identify nodes that critically support amygdalar interactions with the larger brain network. We examined three graph properties, each indexing a different emergent aspect of amygdalar network communication: current-flow betweenness centrality (amygdalar influence on information flowing between other pairs of nodes), node communicability (clarity of communication between the amygdala and other nodes), and subgraph centrality (amygdalar influence over local network processing). Findings demonstrate that each of these aspects of amygdalar communication is associated with separable sets of regions and, in some cases, these sets map onto previously identified sub-circuits. For example, betweenness and communicability were each associated with different sub-circuits that have been identified in previous work as supporting distinct aspects of memory-guided behavior. Other regions identified span basic (e.g., visual cortex) to higher-order (e.g., insula) sensory processing and executive functions (e.g., dorsolateral prefrontal cortex). Present findings expand our current understanding of amygdalar function by showing that there is no single ‘amygdala network’, but rather multiple networks, each supporting different modes of amygdalar interaction with the larger brain network. Additionally, our novel method allowed for the identification of how such regions support the amygdala, which has not been previously explored.

Hippocampal replay reflects specific past experiences rather than a plan for subsequent choice

Executing memory-guided behavior requires storage of information about experience and later recall of that information to inform choices. Awake hippocampal replay, when hippocampal neural ensembles briefly reactivate a representation related to prior experience, has been proposed to critically contribute to these memory-related processes. However, it remains unclear whether awake replay contributes to memory function by promoting the storage of past experiences, facilitating planning based on evaluation of those experiences, or both. We designed a dynamic spatial task that promotes replay before a memory-based choice and assessed how the content of replay related to past and future behavior. We found that replay content was decoupled from subsequent choice and instead was enriched for representations of previously rewarded locations and places that had not been visited recently, indicating a role in memory storage rather than in directly guiding subsequent behavior.

Normal and Abnormal Sharp Wave Ripples in the Hippocampal-Entorhinal Cortex System: Implications for Memory Consolidation, Alzheimer's Disease, and Temporal Lobe Epilepsy

The appearance of hippocampal sharp wave ripples (SWRs) is an electrophysiological biomarker for episodic memory encoding and behavioral planning. Disturbed SWRs are considered a sign of neural network dysfunction that may provide insights into the structural connectivity changes associated with cognitive impairment in early-stage Alzheimer's disease (AD) and temporal lobe epilepsy (TLE). SWRs originating from hippocampus have been extensively studied during spatial navigation in rodents, and more recent studies have investigated SWRs in the hippocampal-entorhinal cortex (HPC-EC) system during a variety of other memory-guided behaviors. Understanding how SWR disruption impairs memory function, especially episodic memory, could aid in the development of more efficacious therapeutics for AD and TLE. In this review, we first provide an overview of the reciprocal association between AD and TLE, and then focus on the functions of HPC-EC system SWRs in episodic memory consolidation. It is posited that these waveforms reflect rapid network interactions among excitatory projection neurons and local interneurons and that these waves may contribute to synaptic plasticity underlying memory consolidation. Further, SWRs appear altered or ectopic in AD and TLE. These waveforms may thus provide clues to understanding disease pathogenesis and may even serve as biomarkers for early-stage disease progression and treatment response.

Mushroom body output differentiates memory processes and distinct memory-guided behaviors

The mushroom body (MB) of Drosophila melanogaster has multiple functions in controlling memory and behavior.1-9 However, circuit mechanisms that generate this functional diversity are largely unclear. Here, we systematically probed the behavioral contribution of each type of MB output neuron (MBON) by blocking during acquisition, retention, or retrieval of reward or punishment memories. We evaluated the contribution using two conditioned responses: memory-guided odor choice and odor source attraction. Quantitative analysis revealed that these conditioned odor responses are controlled by different sets of MBONs. We found that the valence of memory, rather than the transition of memory steps, has a larger impact on the patterns of required MBONs. Moreover, we found that the glutamatergic MBONs forming recurrent circuits commonly contribute to appetitive memory acquisition, suggesting a pivotal role of this circuit motif for reward processing. Our results provide principles how the MB output circuit processes associative memories of different valence and controls distinct memory-guided behaviors.

Temporal Expectations Prepare Visual Working Memory for Behavior.

Working memory enables us to retain past sensations in service of anticipated task demands. How we prepare for anticipated task demands during working memory retention remains poorly understood. Here, we focused on the role of time—asking how temporal expectations help prepare for ensuing memory-guided behavior. We manipulated the expected probe time in a delayed change-detection task and report that temporal expectation can have a profound influence on memory-guided behavioral performance. EEG measurements corroborated the utilization of temporal expectations: demonstrating the involvement of a classic EEG signature of temporal expectation—the contingent negative variation—in the context of working memory. We also report the influence of temporal expectations on 2 EEG signatures associated with visual working memory—the lateralization of 8- to 12-Hz alpha activity, and the contralateral delay activity. We observed a dissociation between these signatures, whereby alpha lateralization (but not the contralateral delay activity) adapted to the time of expected memory utilization. These data show how temporal expectations prepare visual working memory for behavior and shed new light on the electrophysiological markers of both temporal expectation and working memory.

Prospective task knowledge improves working memory-guided behavior

Prospective task knowledge improves working memory-guided behavior

Goal-directed and stimulus-driven selection of internal representations

Adaptive behavior relies on the selection of relevant sensory information from both the external environment and internal memory representations. In understanding external selection, a classic distinction is made between voluntary (goal-directed) and involuntary (stimulus-driven) guidance of attention. We have developed a task-the anti-retrocue task-to separate and examine voluntary and involuntary guidance of attention to internal representations in visual working memory. We show that both voluntary and involuntary factors influence memory performance but do so in distinct ways. Moreover, by tracking gaze biases linked to attentional focusing in memory, we provide direct evidence for an involuntary "retro-capture" effect whereby external stimuli involuntarily trigger the selection of feature-matching internal representations. We show that stimulus-driven and goal-directed influences compete for selection in memory, and that the balance of this competition-as reflected in oculomotor signatures of internal attention-predicts the quality of ensuing memory-guided behavior. Thus, goal-directed and stimulus-driven factors together determine the fate not only of perception, but also of internal representations in working memory.

Trajectory-modulated hippocampal neurons persist throughout memory-guided navigation

Trajectory-dependent splitter neurons in the hippocampus encode information about a rodent’s prior trajectory during performance of a continuous alternation task. As such, they provide valuable information for supporting memory-guided behavior. Here, we employed single-photon calcium imaging in freely moving mice to investigate the emergence and fate of trajectory-dependent activity through learning and mastery of a continuous spatial alternation task. In agreement with others, the quality of trajectory-dependent information in hippocampal neurons correlated with task performance. We thus hypothesized that, due to their utility, splitter neurons would exhibit heightened stability. We find that splitter neurons were more likely to remain active and retained more consistent spatial information across multiple days than other neurons. Furthermore, we find that both splitter neurons and place cells emerged rapidly and maintained stable trajectory-dependent/spatial activity thereafter. Our results suggest that neurons with useful functional coding exhibit heightened stability to support memory guided behavior.

Cognitive Neuroscience: Why Do We Get Lost When We Are Stressed?

A recent study in humans shows that stress increases our reliance on familiar routes during navigation. This research explains how increases in cortisol, a biomarker of stress, disrupts navigation-related brain circuits, resulting in less efficient navigation.

Preparation for upcoming attentional states in the hippocampus and medial prefrontal cortex.

Goal-directed attention is usually studied by providing individuals with explicit instructions on what they should attend to. But in daily life, we often use past experiences to guide our attentional states. Given the importance of memory for predicting upcoming events, we hypothesized that memory-guided attention is supported by neural preparation for anticipated attentional states. We examined preparatory coding in the human hippocampus and mPFC, two regions that are important for memory-guided behaviors, in two tasks: one where attention was guided by memory and another in which attention was explicitly instructed. Hippocampus and mPFC exhibited higher activity for memory-guided vs. explicitly instructed attention. Furthermore, representations in both regions contained information about upcoming attentional states. In the hippocampus, this preparation was stronger for memory-guided attention, and occurred alongside stronger coupling with visual cortex during attentional guidance. These results highlight the mechanisms by which memories are used to prepare for upcoming attentional goals.

Refinement and Reactivation of a Taste-Responsive Hippocampal Network.

Animals need to remember the locations of nourishing and toxic food sources for survival, a fact that necessitates a mechanism for associating taste experiences with particular places. We have previously identified such responses within hippocampal place cells [1], the activity of which is thought to aid memory-guided behavior by forming a mental map of an animal's environment that can be reshaped through experience [2-7]. It remains unknown, however, whether taste responsiveness is intrinsic to asubset of place cells or emerges as a result of experiencethat reorganizes spatial maps. Here, we recorded from neurons in the dorsal CA1 region of rats running for palatable tastes delivered via intra-oral cannulae at specific locations on a linear track. We identified a subset of taste-responsive cells that, even prior to taste exposure, had larger place fields than non-taste-responsive cells overlapping with stimulus delivery zones. Taste-responsive cells' place fields then contracted as a result of taste experience, leading to a stronger representation of stimulus delivery zones on the track. Taste-responsive units exhibited increased sharp-wave ripple co-activation during the taste delivery session and subsequent rest periods, which correlated with the degree of place field contraction. Our results reveal that novel taste experience evokes responses within a preconfigured network of taste-responsive hippocampal place cells with large fields, whose spatial representations are refined by sensory experience to signal areas of behavioral salience. This represents a possible mechanism by which animals identify and remember locations where ecologically relevant stimuli are found within their environment.

Hippocampal theta coordinates memory processing during visual exploration.

The hippocampus supports memory encoding and retrieval, which may occur at distinct phases of the theta cycle. These processes dynamically interact over rapid timescales, especially when sensory information conflicts with memory. The ability to link hippocampal dynamics to memory-guided behaviors has been limited by experiments that lack the temporal resolution to segregate encoding and retrieval. Here, we simultaneously tracked eye movements and hippocampal field potentials while neurosurgical patients performed a spatial memory task. Phase-locking at the peak of theta preceded fixations to retrieved locations, indicating that the hippocampus coordinates memory-guided eye movements. In contrast, phase-locking at the trough of theta followed fixations to novel object-locations and predicted intact memory of the original location. Theta-gamma phase amplitude coupling increased during fixations to conflicting visual content, but predicted memory updating. Hippocampal theta thus supports learning through two interleaved processes: strengthening encoding of novel information and guiding exploration based on prior experience.

Output Planning at the Input Stage: Action Imprinting for Future Memory-Guided Behaviour

Working memory serves as the buffer between past sensations and future behaviour, making it vital to understand not only how we encode and retain information in memory but also how we plan for its upcoming use. We ask when prospective action goals emerge alongside the encoding and retention of detailed sensory information in working memory – whether future action plans emerge gradually during memory delays, or are brought into memory early, in tandem with sensory encoding. To address this, we tracked neural planning for prospective actions in a working-memory task in which detailed visual shape information was linked to specific manual actions after a delay. We show that prospective action plans in human motor cortex emerge early alongside the selective encoding of visual information into memory. This ‘action imprinting’ (1) precedes a second stage of action preparation that adapts to the time of expected memory utilisation, (2) occurs even in face of an intervening motor task, and (3) predicts visual-memory-guided behaviour several seconds later. By bringing prospective action plans into working memory at an early stage, the brain creates a dual (visual-motor) memory code that can make memories more effective and robust for serving future behaviour.

Unexpected Rule-Changes in a Working Memory Task Shape the Firing of Histologically Identified Delay-Tuned Neurons in the Prefrontal Cortex

Working memory-guided behaviors require memory retention during delay periods, when subsets of prefrontal neurons have been reported to exhibit persistently elevated firing. What happens to delay activity when information stored in working memory is no longer relevant for guiding behavior? In this study, we perform juxtacellular recording and labeling of delay-tuned (-elevated or -suppressed) neurons in the prelimbic cortex of freely moving rats, performing a familiar delayed cue-matching-to-place task. Unexpectedly, novel task-rules are introduced, rendering information held in working memory irrelevant. Following successful strategy switching within one session, delay-tuned neurons are filled with neurobiotin for histological analysis. Delay-elevated neurons include pyramidal cells with large heterogeneity of soma-dendritic distribution, molecular expression profiles, and task-relevant activity. Rule change induces heterogenous adjustments on individual neurons and ensembles' activity but cumulates in balanced firing rate reorganizations across cortical layers. Our results demonstrate divergent cellular and network dynamics when an abrupt change in task rules interferes with working memory.

Neurophysiological coding of space and time in the hippocampus, entorhinal cortex, and retrosplenial cortex.

Neurophysiological recordings in behaving rodents demonstrate neuronal response properties that may code space and time for episodic memory and goal-directed behaviour. Here, we review recordings from hippocampus, entorhinal cortex, and retrosplenial cortex to address the problem of how neurons encode multiple overlapping spatiotemporal trajectories and disambiguate these for accurate memory-guided behaviour. The solution could involve neurons in the entorhinal cortex and hippocampus that show mixed selectivity, coding both time and location. Some grid cells and place cells that code space also respond selectively as time cells, allowing differentiation of time intervals when a rat runs in the same location during a delay period. Cells in these regions also develop new representations that differentially code the context of prior or future behaviour allowing disambiguation of overlapping trajectories. Spiking activity is also modulated by running speed and head direction, supporting the coding of episodic memory not as a series of snapshots but as a trajectory that can also be distinguished on the basis of speed and direction. Recent data also address the mechanisms by which sensory input could distinguish different spatial locations. Changes in firing rate reflect running speed on long but not short time intervals, and few cells code movement direction, arguing against path integration for coding location. Instead, new evidence for neural coding of environmental boundaries in egocentric coordinates fits with a modelling framework in which egocentric coding of barriers combined with head direction generates distinct allocentric coding of location. The egocentric input can be used both for coding the location of spatiotemporal trajectories and for retrieving specific viewpoints of the environment. Overall, these different patterns of neural activity can be used for encoding and disambiguation of prior episodic spatiotemporal trajectories or for planning of future goal-directed spatiotemporal trajectories.

Distinct Neural Circuits Underlie Prospective and Concurrent Memory-Guided Behavior

The past is the best predictor of the future. This simple postulate belies the complex neurobiological mechanisms that facilitate an individual's use of memory to guide decisions. Previous research has shown integration of memories bias decision-making. Alternatively, memories can prospectively guide our choices. Here, we elucidate the mechanisms and timing of hippocampal (HPC), medial prefrontal cortex (mPFC), and striatal contributions during prospective memory-guided decision-making. We develop an associative learning task in which the correct choice is conditional on the preceding stimulus. Two distinct networks emerge: (1) a prospective circuit consisting of the HPC, putamen, mPFC, and other cortical regions, which exhibit increased activation preceding successful conditional decisions and (2) a concurrent circuit comprising the caudate, dorsolateral prefrontal cortex (dlPFC), and additional cortical structures that engage during the execution of correct conditional choices. Our findings demonstrate distinct neurobiological circuits through which memory prospectively biases decisions and influences choice execution.

Short-Term Influence of Recent Trial History on Perceptual Choice Changes with Stimulus Strength

Perceptual decisions, especially for difficult stimuli, can be influenced by choices and outcomes in previous trials. However, it is not well understood how stimulus strength modulates the temporal characteristics as well as the magnitude of trial history influence. We addressed this question using a contrast detection task in freely moving mice. We found that, at lower as compared to higher stimulus contrast, the current choice of the mice was more influenced by choices and outcomes in the past trials and the influence emerged from a longer history. To examine the neural basis of stimulus strength-dependent history influence, we recorded from the secondary motor cortex (M2), a prefrontal region that plays an important role in cue-guided actions and memory-guided behaviors. We found that more M2 neurons conveyed information about choices on the past two trials at lower than at higher contrast. Furthermore, history-trial activity in M2 was important for decoding upcoming choice at low contrast. Thus, trial history influence of perceptual choice is adaptive to the strength of sensory evidence, which may be important for action selection in a dynamic environment.

Courtship behavior induced by appetitive olfactory memory

Reinforcement signals such as food reward and noxious punishment can change diverse behaviors. This holds true in fruit flies, Drosophila melanogaster, which can be conditioned by an odor and sugar reward or electric shock punishment. Despite a wide variety of behavior modulated by learning, conditioned responses have been traditionally measured by altered odor preference in a choice, and other memory-guided behaviors have been only scarcely investigated. Here, we analyzed detailed conditioned odor responses of flies after sugar associative learning by employing a video recording and semi-automated processing pipeline. Trajectory analyses revealed that multiple behavioral components were altered along with conditioned approach to the rewarded odor. Notably, we found that lateral wing extension, a hallmark of courtship behavior of D. melanogaster, was robustly increased specifically in the presence of the rewarded odor. Strikingly, genetic disruption of the mushroom body output did not impair conditioned courtship increase, while markedly weakening conditioned odor approach. Our results highlight the complexity of conditioned responses and their distinct regulatory mechanisms that may underlie coordinated yet complex memory-guided behaviors in flies.