4.4 Review

Assessments of dentate gyrus function: discoveries and debates

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Article Cell Biology

Global remapping in granule cells and mossy cells of the mouse dentate gyrus

Sang Hoon Kim et al.

Summary: Hippocampal place cells in the dentate gyrus (DG) exhibit spatially modulated firing, and previous studies have drawn different conclusions about their remapping and role in encoding context specificity. By recording granule cells and mossy cells, two populations of place cells in the DG, as mice foraged in different environments, we found that both cell types remapped robustly but through different mechanisms, contributing to orthogonal representations of distinct spatial contexts.

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Article Biochemistry & Molecular Biology

Flexible encoding of objects and space in single cells of the dentate gyrus

Douglas GoodSmith et al.

Summary: The neurons in the dentate gyrus (DG) region of the hippocampus are able to integrate spatial and nonspatial information, forming memories of space and associated stimuli. This study reveals the ability of DG cells to detect changes in the environment and maintain a stable spatial representation.

CURRENT BIOLOGY (2022)

Review Neurosciences

Forgetting as a form of adaptive engram cell plasticity

Tomas J. Ryan et al.

Summary: Understanding the mechanisms of forgetting encoded memories can provide insights into adaptive forgetting and pathological memory loss. Forgetting involves neuroplasticity that changes the accessibility of engram cells and is influenced by changes in environmental predictability. Forgetting occurs when engram cells cannot be reactivated, and it involves circuit remodelling. Different forms of forgetting vary in their mechanisms, time course, and reversibility, but all forms involve switching engram cells from an accessible state to an inaccessible state.

NATURE REVIEWS NEUROSCIENCE (2022)

Review Neurosciences

The fasciola cinereum subregion of the hippocampus is important for the acquisition of visual contextual memory

Seong-Beom Park et al.

Summary: The fasciola cinereum (FC) is a subregion of the hippocampus that shows clear anatomical borders with the CA1 and receives inputs from the lateral entorhinal cortex and perirhinal cortex while projecting exclusively to the crest of the DG. Neurotoxic lesions in the FC impair visual contextual memory acquisition and place recognition in rats, suggesting a critical role in contextual pattern separation in the hippocampus.

PROGRESS IN NEUROBIOLOGY (2022)

Article Neurosciences

Adult-born dentate granule cells promote hippocampal population sparsity

Stephen B. McHugh et al.

Summary: The study reveals the crucial role of adult-born granule cells (abDGCs) in controlling the information processing in the hippocampus by promoting sparser population firing and enhancing responses to novel stimuli.

NATURE NEUROSCIENCE (2022)

Article Biochemistry & Molecular Biology

Ventro-dorsal Hippocampal Pathway Gates Novelty-Induced Contextual Memory Formation

Felipe Fredes et al.

Summary: The study demonstrates the important role of a pathway between ventral mossy cells and dorsal granule cells in the hippocampus in the formation of novelty-induced memory, influencing the activation of dorsal granule cells through excitatory transmission; furthermore, the manipulation of ventral mossy cell activity can bidirectionally regulate the acquisition of novelty-induced contextual memory.

CURRENT BIOLOGY (2021)

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Has the hippocampus really forgotten about space?

Judit Fiedler et al.

Summary: The hippocampus is not only used for navigating the environment and storing spatial memories, but may also play a role in episodic memory. Recent evidence questions the primacy of space and suggests that the challenge for mammalian hippocampal circuitry lies in handling memory load, whether spatial or not.

CURRENT OPINION IN NEUROBIOLOGY (2021)

Article Neurosciences

Bidirectional Regulation of Cognitive and Anxiety-like Behaviors by Dentate Gyrus Mossy Cells in Male and Female Mice

Justin J. Botterill et al.

Summary: The dentate gyrus (DG) of the hippocampus plays a crucial role in cognition and behavior, with mossy cells (MCs) potentially regulating anxiety-like behaviors and cognitive performance in specific ways. Manipulations of MCs can bidirectionally influence behaviors by activating or inhibiting MCs. Sex-specific effects were observed in some behaviors, with females showing more pronounced effects than males.

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Article Multidisciplinary Sciences

Gamma rhythm communication between entorhinal cortex and dentate gyrus neuronal assemblies

Antonio Fernandez-Ruiz et al.

Summary: Gamma oscillations coordinate spike timing of functionally specialized neuronal ensembles across different brain regions, impacting learning tasks and transmitting task-relevant information in the entorhinal-hippocampal circuit, serving as a mechanism of neuronal communication.

SCIENCE (2021)

Article Neurosciences

Dynamic interplay between GABAergic networks and developing neurons in the adult hippocampus

Mariela F. Trinchero et al.

Summary: Neurogenesis is a powerful mechanism for structural and functional remodeling in restricted areas of the adult brain, with GABA playing a key role in regulating neural stem cell quiescence to neuronal maturation. The complexity is further enhanced by feedback and feedforward networks that impact the development and function of new neurons. Ultimately, newly generated granule cells connect with input and output partners in a manner largely influenced by local circuit activity.

CURRENT OPINION IN NEUROBIOLOGY (2021)

Article Biochemistry & Molecular Biology

The temporal origin of dentate granule neurons dictates their role in spatial memory

Nuria Masachs et al.

Summary: The dentate gyrus is one of the only brain regions that continues its development after birth in rodents. Adolescence is a sensitive period during which cognitive competences are programmed. Research found that neurons generated during adolescence are transiently involved in spatial memory processing, while adult-generated neurons are recruited at a later time point when animals are older.

MOLECULAR PSYCHIATRY (2021)

Review Neurosciences

The grid code for ordered experience

Jon W. Rueckemann et al.

Summary: Researchers propose that hippocampal input drives the grid cell network in both spatial and non-spatial contexts, with interactions between the hippocampus and entorhinal cortex building a topological representation based on temporal ordering of events.

NATURE REVIEWS NEUROSCIENCE (2021)

Article Cell Biology

Cholinergic modulation of dentate gyrus processing through dynamic reconfiguration of inhibitory circuits

Mora B. Ogando et al.

Summary: The cholinergic modulation enhances the response of mature granule cells to afferent stimuli through precise reconfiguration of inhibitory circuits. This mechanism allows mature granule cells to escape strong inhibition, creating plasticity and promoting memory formation.

CELL REPORTS (2021)

Article Cell Biology

Dentate spikes and external control of hippocampal function

Dino Dvorak et al.

Summary: This study reveals that events initiated by different brain regions can affect the discharge patterns in the CA1 area, and during slow gamma dominance, hippocampal discharge will switch to represent distant recollected locations. This indicates that different types of events and oscillations in the hippocampal region can promote specific modes of information processing when interacting within and across brain regions.

CELL REPORTS (2021)

Article Neurosciences

Adult neurogenesis mediates forgetting of multiple types of memory in the rat

Gavin A. Scott et al.

Summary: Investigations using rats show that neurogenesis-induced forgetting occurs across different behavioral tasks, even with varying levels of training intensity. The results suggest that forgetting due to neurogenesis is a conserved mechanism that aids in the clearance of memories.

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How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex-dentate gyrus-CA3 network

S. Jose Guzman et al.

Summary: Pattern separation is a fundamental brain computation that transforms small differences in input patterns into large differences in output patterns. External gamma-modulated inhibition and internal lateral inhibition are important mechanisms for pattern separation, while local connectivity and fast signaling play crucial roles in maximizing effectiveness. Specific properties of cells and synapses optimize higher-order computations in biological networks and have the potential to enhance deep learning capabilities in technical networks.

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Egocentric and allocentric representations of space in the rodent brain

Cheng Wang et al.

CURRENT OPINION IN NEUROBIOLOGY (2020)

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Dentate gyrus circuits for encoding, retrieval and discrimination of episodic memories

Thomas Hainmueller et al.

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Memory engrams: Recalling the past and imagining the future

Sheena A. Josselyn et al.

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Functionally Distinct Neuronal Ensembles within the Memory Engram

Xiaochen Sun et al.

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The Dentate Gyrus Classifies Cortical Representations of Learned Stimuli

Nicholas I. Woods et al.

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A Distributed Neural Code in the Dentate Gyrus and in CA1

Fabio Stefanini et al.

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Parallel processing streams in the hippocampus

Heekyung Lee et al.

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Place cell maps slowly develop via competitive learning and conjunctive coding in the dentate gyrus

Soyoun Kim et al.

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Abolition of aberrant neurogenesis ameliorates cognitive impairment after stroke in mice

Maria Isabel Cuartero et al.

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Re-evaluating Circuit Mechanisms Underlying Pattern Separation

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Recalibrating the Relevance of Adult Neurogenesis

Jason S. Snyder

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Distinct hippocampal engrams control extinction and relapse of fear memory

Anthony F. Lacagnina et al.

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Functions of adult-born neurons in hippocampal memory interference and indexing

Samara M. Miller et al.

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Forgetting at biologically realistic levels of neurogenesis in a large-scale hippocampal model

Lina M. Tran et al.

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Human Adult Neurogenesis: Evidence and Remaining Questions

Gerd Kempermann et al.

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Recovery of Lost Infant Memories in Mice

Axel Guskjolen et al.

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On How the Dentate Gyrus Contributes to Memory Discrimination

Milenna Tamara van Dijk et al.

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Parallel emergence of stable and dynamic memory engrams in the hippocampus

Thomas Hainmueller et al.

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Integrating time from experience in the lateral entorhinal cortex

Albert Tsao et al.

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Does Adult Neurogenesis Persist in the Human Hippocampus?

Mercedes F. Paredes et al.

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Adult Hippocampal Neurogenesis: A Coming-of-Age Story

H. Georg Kuhn et al.

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Egocentric coding of external items in the lateral entorhinal cortex

Cheng Wang et al.

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In Vivo Imaging of Dentate Gyrus Mossy Cells in Behaving Mice

Nathan B. Danielson et al.

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Separation or binding? Role of the dentate gyrus in hippocampal mnemonic processing

Jong Won Lee et al.

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On the `data stirring' role of the dentate gyrus of the hippocampus

Charles R. Legendy

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Engrams and circuits crucial for systems consolidation of a memory

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From Engrams to Pathologies of the Brain

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Reflections on the Structural-Functional Evolution of the Hippocampus: What Is the Big Deal about a Dentate Gyrus?

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The enigmatic mossy cell of the dentate gyrus

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Tracking the flow of hippocampal computation: Pattern separation, pattern completion, and attractor dynamics

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Rapid erasure of hippocampal memory following inhibition of dentate gyrus granule cells

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Dynamic role of adult-born dentate granule cells in memory processing

Emilio Kropff et al.

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Engram cells retain memory under retrograde amnesia

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Adult Hippocampal Neurogenesis in Natural Populations of Mammals

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Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline

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Precise Spatial Coding is Preserved Along the Longitudinal Hippocampal Axis

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Functional correlates of the lateral and medial entorhinal cortex: objects, path integration and local - global reference frames

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Place cells in the hippocampus: Eleven maps for eleven rooms

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Hippocampal Neurogenesis Regulates Forgetting During Adulthood and Infancy

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Expression of c-fos in hilar mossy cells of the dentate gyrus in vivo

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Molecular layer perforant path-associated cells contribute to feed-forward inhibition in the adult dentate gyrus

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Creating a False Memory in the Hippocampus

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Neurogenesis in the dentate gyrus: carrying the message or dictating the tone

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Spatial Firing Correlates of Physiologically Distinct Cell Types of the Rat Dentate Gyrus

Joshua P. Neunuebel et al.

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Optogenetic stimulation of a hippocampal engram activates fear memory recall

Xu Liu et al.

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Serotonin receptor expression along the dorsal-ventral axis of mouse hippocampus

Kenji F. Tanaka et al.

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The Race to Learn: Spike Timing and STDP Can Coordinate Learning and Recall in CA3

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Pattern Separation in the Dentate Gyrus: A Role for the CA3 Backprojection

Catherine E. Myers et al.

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Pattern separation in the hippocampus

Michael A. Yassa et al.

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Frequency-Tuned Distribution of Inhibition in the Dentate Gyrus

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Distinct Representations and Theta Dynamics in Dorsal and Ventral Hippocampus

Sebastien Royer et al.

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Are the Dorsal and Ventral Hippocampus Functionally Distinct Structures?

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How Informative Are Spatial CA3 Representations Established by the Dentate Gyrus?

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The role of competitive learning in the generation of DG fields from EC inputs

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Computational Influence of Adult Neurogenesis on Memory Encoding

James B. Aimone et al.

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A Functional Role for Adult Hippocampal Neurogenesis in Spatial Pattern Separation

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The hippocampal dentate gyrus is essential for generating contextual memories of fear and drug-induced reward

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What is the mammalian dentate gyrus good for?

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Structural determinants of transmission at large hippocampal mossy fiber Synapses

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Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus

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Potential role for adult neurogenesis in the encoding of time in new memories

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Neuronal differentiation in the adult hippocampus recapitulates embryonic development

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Microstructure of a spatial map in the entorhinal cortex

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The role of hippocampal subregions in detecting spatial novelty

I Lee et al.

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Granule cell number, cell death and cell proliferation in the dentate gyrus of wild-living rodents

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Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus

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Structural and functional asymmetry in the normal and epileptic rat dentate gyrus

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