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Nature Neuroscience Oct 2017The hippocampus serves a critical function in memory, navigation, and cognition. asked John Lisman to lead a group of researchers in a dialog on shared and distinct... (Review)
Review
The hippocampus serves a critical function in memory, navigation, and cognition. asked John Lisman to lead a group of researchers in a dialog on shared and distinct viewpoints on the hippocampus. There has been a long history of studying the hippocampus, but recent work has made it possible to study the cellular and network basis of defined operations—operations that include cognitive processes that have been otherwise difficult to study (see Box 1 for useful terminology). These operations deal with the context-dependent representation of complex memories, the role of mental exploration based on imagined rather than real movements, and the use of recalled information for navigation and decision-making. The progress that has been made in understanding the hippocampus has motivated the study of other brain regions that provide hippocampal input or receive hippocampal output; the hippocampus is thus serving as a nucleating point for the larger goal of understanding the neural codes that allow inter-regional communication and more generally, understanding how memory-guided behavior is achieved by large scale integration of brain regions. In generating a discussion among experts in the study of the cognitive processes of the hippocampus, the editors and I have posed questions that probe important principles of hippocampal function. We hope that the resulting discussion will make clear to readers the progress that has been made, while also identifying issues where consensus has not yet been achieved and that should be pursued in future research. – John Lisman
Topics: Animals; Cognition; Hippocampus; Humans; Memory; Spatial Navigation
PubMed: 29073641
DOI: 10.1038/nn.4661 -
Trends in Neurosciences Oct 2011The ability to discriminate among similar experiences is a crucial feature of episodic memory. This ability has long been hypothesized to require the hippocampus, and... (Review)
Review
The ability to discriminate among similar experiences is a crucial feature of episodic memory. This ability has long been hypothesized to require the hippocampus, and computational models suggest that it is dependent on pattern separation. However, empirical data for the role of the hippocampus in pattern separation have not been available until recently. This review summarizes data from electrophysiological recordings, lesion studies, immediate-early gene imaging, transgenic mouse models, as well as human functional neuroimaging, that provide convergent evidence for the involvement of particular hippocampal subfields in this key process. We discuss the impact of aging and adult neurogenesis on pattern separation, and also highlight several challenges to linking across species and approaches, and suggest future directions for investigation.
Topics: Animals; Electrophysiology; Functional Neuroimaging; Genes, Immediate-Early; Hippocampus; Humans; Memory; Models, Neurological; Nerve Net
PubMed: 21788086
DOI: 10.1016/j.tins.2011.06.006 -
Nature Reviews. Neuroscience Mar 2016The brain creates a model of the world around us. We can use this representation to perceive and comprehend what we see at any given moment, but also to vividly... (Review)
Review
The brain creates a model of the world around us. We can use this representation to perceive and comprehend what we see at any given moment, but also to vividly re-experience scenes from our past and imagine future (or even fanciful) scenarios. Recent work has shown that these cognitive functions--perception, imagination and recall of scenes and events--all engage the anterior hippocampus. In this Opinion article, we capitalize on new findings from functional neuroimaging to propose a model that links high-level cognitive functions to specific structures within the anterior hippocampus.
Topics: Animals; Hippocampus; Humans; Imagination; Memory, Episodic; Perception
PubMed: 26865022
DOI: 10.1038/nrn.2015.24 -
Current Biology : CB Dec 2015
Topics: Animals; Hippocampus; Humans; Memory; Memory, Episodic
PubMed: 26654366
DOI: 10.1016/j.cub.2015.10.049 -
Neuron Jul 2021The hippocampus supports many facets of cognition, including learning, memory, and emotional processing. Anatomically, the hippocampus runs along a longitudinal axis,...
The hippocampus supports many facets of cognition, including learning, memory, and emotional processing. Anatomically, the hippocampus runs along a longitudinal axis, posterior to anterior in primates. The structure, function, and connectivity of the hippocampus vary along this axis. In human hippocampus, longitudinal functional heterogeneity remains an active area of investigation, and structural heterogeneity has not been described. To understand the cellular and molecular diversity along the hippocampal long axis in human brain and define molecular signatures corresponding to functional domains, we performed single-nuclei RNA sequencing on surgically resected human anterior and posterior hippocampus from epilepsy patients, identifying differentially expressed genes at cellular resolution. We further identify axis- and cell-type-specific gene expression signatures that differentially intersect with human genetic signals, identifying cell-type-specific genes in the posterior hippocampus for cognitive function and the anterior hippocampus for mood and affect. These data are accessible as a public resource through an interactive website.
Topics: Female; Gene Expression; Gene Expression Profiling; Hippocampus; Humans; Male; Microglia; Neurons; Sequence Analysis, RNA
PubMed: 34051145
DOI: 10.1016/j.neuron.2021.05.003 -
Hippocampus Oct 2015Sharp wave ripples (SPW-Rs) represent the most synchronous population pattern in the mammalian brain. Their excitatory output affects a wide area of the cortex and... (Review)
Review
Sharp wave ripples (SPW-Rs) represent the most synchronous population pattern in the mammalian brain. Their excitatory output affects a wide area of the cortex and several subcortical nuclei. SPW-Rs occur during "off-line" states of the brain, associated with consummatory behaviors and non-REM sleep, and are influenced by numerous neurotransmitters and neuromodulators. They arise from the excitatory recurrent system of the CA3 region and the SPW-induced excitation brings about a fast network oscillation (ripple) in CA1. The spike content of SPW-Rs is temporally and spatially coordinated by a consortium of interneurons to replay fragments of waking neuronal sequences in a compressed format. SPW-Rs assist in transferring this compressed hippocampal representation to distributed circuits to support memory consolidation; selective disruption of SPW-Rs interferes with memory. Recently acquired and pre-existing information are combined during SPW-R replay to influence decisions, plan actions and, potentially, allow for creative thoughts. In addition to the widely studied contribution to memory, SPW-Rs may also affect endocrine function via activation of hypothalamic circuits. Alteration of the physiological mechanisms supporting SPW-Rs leads to their pathological conversion, "p-ripples," which are a marker of epileptogenic tissue and can be observed in rodent models of schizophrenia and Alzheimer's Disease. Mechanisms for SPW-R genesis and function are discussed in this review.
Topics: Animals; Biomarkers; Brain Waves; Executive Function; Hippocampus; Humans; Memory, Episodic
PubMed: 26135716
DOI: 10.1002/hipo.22488 -
Molecular Psychiatry Jan 2019Adult neurogenesis in the dentate gyrus of the hippocampus is highly regulated by a number of environmental and cell-intrinsic factors to adapt to environmental changes.... (Review)
Review
Adult neurogenesis in the dentate gyrus of the hippocampus is highly regulated by a number of environmental and cell-intrinsic factors to adapt to environmental changes. Accumulating evidence suggests that adult-born neurons may play distinct physiological roles in hippocampus-dependent functions, such as memory encoding and mood regulation. In addition, several brain diseases, such as neurological diseases and mood disorders, have deleterious effects on adult hippocampal neurogenesis, and some symptoms of those diseases can be partially explained by the dysregulation of adult hippocampal neurogenesis. Here we review a possible link between the physiological functions of adult-born neurons and their roles in pathological conditions.
Topics: Adult; Affect; Brain; Brain Diseases; Dentate Gyrus; Hippocampus; Humans; Memory; Neurogenesis; Neuronal Plasticity; Neurons; Temporal Lobe
PubMed: 29679070
DOI: 10.1038/s41380-018-0036-2 -
Behavioural Brain Research May 2015The novel object recognition (NOR) task has emerged as a popular method for testing the neurobiology of nonspatial memory in rodents. This task exploits the natural... (Review)
Review
The novel object recognition (NOR) task has emerged as a popular method for testing the neurobiology of nonspatial memory in rodents. This task exploits the natural tendency of rodents to explore novel items and depending on the amount of time that rodents spend exploring the presented objects, inferences about memory can be established. Despite its wide use, the underlying neural circuitry and mechanisms supporting NOR have not been clearly defined. In particular, considerable debate has focused on whether the hippocampus plays a significant role in the object memory that is encoded, consolidated and then retrieved during discrete stages of the NOR task. Here we analyzed the results of all published reports in which the role of the rodent hippocampus in object memory was inferred from performance in the task with restricted parameters. We note that the remarkable variability in NOR methods across studies complicates the ability to draw meaningful conclusions from the work. Focusing on 12 reports in which a minimum criterion of sample session object exploration was imposed, we find that temporary or permanent lesion of the hippocampus consistently disrupts object memory when a delay of 10 min or greater is imposed between the sample and test sessions. We discuss the significance of a delay-dependent role of the hippocampus in NOR within the framework of the medial temporal lobe. We assert that standardization of the NOR protocol is essential for obtaining reliable data that can then be compared across studies to build consensus as to the specific contribution of the rodent hippocampus to object memory.
Topics: Animals; Hippocampus; Mice; Neuropsychological Tests; Rats; Recognition, Psychology
PubMed: 25169255
DOI: 10.1016/j.bbr.2014.08.002 -
Hippocampus Mar 2023The hippocampus is composed of various subregions: CA1, CA2, CA3, and the dentate gyrus (DG). Despite the abundant hippocampal research literature, until recently, CA2... (Review)
Review
The hippocampus is composed of various subregions: CA1, CA2, CA3, and the dentate gyrus (DG). Despite the abundant hippocampal research literature, until recently, CA2 received little attention. The development of new genetic and physiological tools allowed recent studies characterizing the unique properties and functional roles of this hippocampal subregion. Despite its small size, the cellular content of CA2 is heterogeneous at the molecular and physiological levels. CA2 has been heavily implicated in social behaviors, including social memory. More generally, the mechanisms by which the hippocampus is involved in memory include the reactivation of neuronal ensembles following experience. This process is coordinated by synchronous network events known as sharp-wave ripples (SWRs). Recent evidence suggests that CA2 plays an important role in the generation of SWRs. The unique connectivity and physiological properties of CA2 pyramidal cells make this region a computational hub at the core of hippocampal information processing. Here, we review recent findings that support the role of CA2 in coordinating hippocampal network dynamics from a systems neuroscience perspective.
Topics: Hippocampus; Pyramidal Cells; Neurons; Cognition; Social Behavior; CA3 Region, Hippocampal; CA1 Region, Hippocampal
PubMed: 36575880
DOI: 10.1002/hipo.23495 -
Cell Jun 2014The way the hippocampus processes information and encodes memories in the form of "cell assemblies" is likely determined in part by how its circuits are wired up during...
The way the hippocampus processes information and encodes memories in the form of "cell assemblies" is likely determined in part by how its circuits are wired up during development. In this issue, Xu et al. now provide new insight into how neurons arising from a single common precursor migrate to their final destination and form functionally synchronous ensembles.
Topics: Animals; Hippocampus
PubMed: 24949961
DOI: 10.1016/j.cell.2014.05.032