-
The Journal of Comparative Neurology Dec 2002The rat dentate gyrus is usually described as relatively homogeneous. Here, we present anatomic and physiological data which demonstrate that there are striking...
The rat dentate gyrus is usually described as relatively homogeneous. Here, we present anatomic and physiological data which demonstrate that there are striking differences between the supra- and infrapyramidal blades after status epilepticus and recurrent seizures. These differences appear to be an accentuation of a subtle asymmetry present in normal rats. In both pilocarpine and kainic acid models, there was greater mossy fiber sprouting in the infrapyramidal blade. This occurred primarily in the middle third of the hippocampus. Asymmetric sprouting was evident both with Timm stain as well as antisera to brain-derived neurotrophic factor (BDNF) or neuropeptide Y (NPY). In addition, surviving NPY-immunoreactive hilar neurons were distributed preferentially in the suprapyramidal region of the hilus. Extracellular recordings from infrapyramidal sites in hippocampal slices of pilocarpine-treated rats showed larger population spikes and weaker paired-pulse inhibition in response to perforant path stimulation relative to suprapyramidal recordings. A single stimulus could evoke burst discharges in infrapyramidal granule cells but not suprapyramidal blade neurons. BDNF exposure led to spontaneous epileptiform discharges that were larger in amplitude and longer lasting in the infrapyramidal blade. Stimulation of the infrapyramidal molecular layer evoked larger responses in area CA3 than suprapyramidal stimulation. In slices from the temporal pole, in which anatomic evidence of asymmetry waned, there was little evidence of physiological asymmetry either. Of interest, some normal rats also showed signs of greater evoked responses in the infrapyramidal blade, and this could be detected with both microelectrode recording and optical imaging techniques. Although there were no signs of hyperexcitability in normal rats, the data suggest that there is some asymmetry in the normal dentate gyrus and this asymmetry is enhanced by seizures. Taken together, the results suggest that supra- and infrapyramidal blades of the dentate gyrus could have different circuit functions and that the infrapyramidal blade may play a greater role in activating the hippocampus.
Topics: Animals; Brain-Derived Neurotrophic Factor; Dentate Gyrus; Electrophysiology; Excitatory Amino Acid Agonists; Immunohistochemistry; Kainic Acid; Male; Mossy Fibers, Hippocampal; Muscarinic Agonists; Neuropeptide Y; Pilocarpine; Rats; Rats, Sprague-Dawley; Seizures; Status Epilepticus; Synapses
PubMed: 12455007
DOI: 10.1002/cne.10449 -
Reviews in the Neurosciences Jul 2017Understanding hippocampal (HC) function, as it is presently known, includes exploring the HC role in episodic memory storage. As pointed out by Teyler and DiScenna in... (Review)
Review
Understanding hippocampal (HC) function, as it is presently known, includes exploring the HC role in episodic memory storage. As pointed out by Teyler and DiScenna in the 1980s, the apparatus needed for recalling a stored episode, and awakening all its components in a coordinated manner, by necessity includes a triggering device able to reach each of the mental entities that must be awakened. In the context of neuronal networks, the triggering device in question takes the form of a large cell assembly, a separate one made for every new episode stored. The present paper deals with the creation and the properties of these cell assemblies ('pointer groups'). To perform the function of episodic memory retrieval, each of these must possess the information capacity (entropy) enabling it to single out an episode and the network connections enabling it to reach all components of it; further, to deal with the unpredictability of the memory items it has to address, it must have its member neurons well distributed through the length of the network (the HC). The requirements imply that the creation of a pointer group must include a randomizing step analogous to 'stirring'. It is argued that many of the known peculiarities of granule cells in the dentate gyrus arise as solutions to the practical problems presented by the creation of the pointer groups and the details of 'stirring', and so do a series of other features of the HC network, some of them only discovered in the last few years.
Topics: Animals; Dentate Gyrus; Humans; Memory; Models, Neurological; Neurons; Theta Rhythm
PubMed: 28593904
DOI: 10.1515/revneuro-2016-0080 -
Learning & Memory (Cold Spring Harbor,... Nov 2013In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the... (Review)
Review
In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity after the perinatal period suggests that unique aspects of the structure and function of DG and olfactory bulb circuits allow them to benefit from the adult generation of neurons. In this review, we consider the distinctive features of the DG that may account for it being able to profit from this singular form of neural plasticity. Approaches to the problem of neurogenesis are grouped as "bottom-up," where the phenotype of adult-born granule cells is contrasted to that of mature developmentally born granule cells, and "top-down," where the impact of altering the amount of neurogenesis on behavior is examined. We end by considering the primary implications of these two approaches and future directions.
Topics: Animals; Dentate Gyrus; Neurogenesis; Neurons
PubMed: 24255101
DOI: 10.1101/lm.026542.112 -
Neuron Sep 2009Both conscious and unconscious memory mechanisms contribute to the rewarding effects of nicotine and other drugs of abuse. In this issue of Neuron, Tang and Dani use in...
Both conscious and unconscious memory mechanisms contribute to the rewarding effects of nicotine and other drugs of abuse. In this issue of Neuron, Tang and Dani use in vivo measures of synaptic plasticity in freely moving mice to link nicotine-induced dopamine release in hippocampus to LTP induction and behavioral reinforcement.
Topics: Animals; Behavior, Animal; Dentate Gyrus; Dopamine; Dose-Response Relationship, Drug; Hippocampus; Long-Term Potentiation; Mice; Nicotine; Nicotinic Agonists; Reinforcement, Psychology; Substance-Related Disorders
PubMed: 19755099
DOI: 10.1016/j.neuron.2009.08.029 -
Neurobiology of Learning and Memory Sep 2021At the encounter with a novel environment, contextual memory formation is greatly enhanced, accompanied with increased arousal and active exploration. Although this... (Review)
Review
At the encounter with a novel environment, contextual memory formation is greatly enhanced, accompanied with increased arousal and active exploration. Although this phenomenon has been widely observed in animal and human daily life, how the novelty in the environment is detected and contributes to contextual memory formation has lately started to be unveiled. The hippocampus has been studied for many decades for its largely known roles in encoding spatial memory, and a growing body of evidence indicates a differential involvement of dorsal and ventral hippocampal divisions in novelty detection. In this brief review article, we discuss the recent findings of the role of mossy cells in the ventral hippocampal moiety in novelty detection and put them in perspective with other novelty-related pathways in the hippocampus. We propose a mechanism for novelty-driven memory acquisition in the dentate gyrus by the direct projection of ventral mossy cells to dorsal dentate granule cells. By this projection, the ventral hippocampus sends novelty signals to the dorsal hippocampus, opening a gate for memory encoding in dentate granule cells based on information coming from the entorhinal cortex. We conclude that, contrary to the presently accepted functional independence, the dorsal and ventral hippocampi cooperate to link the novelty and contextual information, and this dorso-ventral interaction is crucial for the novelty-dependent memory formation.
Topics: Animals; Dentate Gyrus; Hippocampus; Humans; Mossy Fibers, Hippocampal; Neural Pathways; Neurons; Open Field Test; Recognition, Psychology
PubMed: 34214666
DOI: 10.1016/j.nlm.2021.107486 -
Frontiers in Neural Circuits 2013The adult brain is in a continuous state of remodeling. This is nowhere more true than in the dentate gyrus, where competing forces such as neurodegeneration and... (Review)
Review
The adult brain is in a continuous state of remodeling. This is nowhere more true than in the dentate gyrus, where competing forces such as neurodegeneration and neurogenesis dynamically modify neuronal connectivity, and can occur simultaneously. This plasticity of the adult nervous system is particularly important in the context of traumatic brain injury or deafferentation. In this review, we summarize a classic injury model, lesioning of the perforant path, which removes the main extrahippocampal input to the dentate gyrus. Early studies revealed that in response to deafferentation, axons of remaining fiber systems and dendrites of mature granule cells undergo lamina-specific changes, providing one of the first examples of structural plasticity in the adult brain. Given the increasing role of adult-generated new neurons in the function of the dentate gyrus, we also compare the response of newborn and mature granule cells following lesioning of the perforant path. These studies provide insights not only to plasticity in the dentate gyrus, but also to the response of neural circuits to brain injury.
Topics: Animals; Brain Injuries; Dentate Gyrus; Disease Models, Animal; Humans; Neurogenesis; Neuronal Plasticity; Perforant Pathway
PubMed: 23423628
DOI: 10.3389/fncir.2013.00017 -
Genes & Development May 2012Stem cells have captured our imagination and generated hope, representing a source of replacement cells to treat a host of medical conditions. Tucked away in specialized... (Review)
Review
Stem cells have captured our imagination and generated hope, representing a source of replacement cells to treat a host of medical conditions. Tucked away in specialized niches, stem cells maintain tissue function and rejuvenate organs. Balancing the equation between cellular supply and demand is especially important in the adult brain, as neural stem cells (NSCs) in two discrete regions, the subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ) next to the lateral ventricles, continuously self-renew and differentiate into neurons in a process called adult neurogenesis. Through the interplay of intrinsic and extrinsic factors, adult neurogenic niches ensure neuronal turnover throughout life, contributing to plasticity and homeostatic processes in the brain. This review summarizes recent progress on the molecular control of adult neurogenesis in the SGZ and SVZ, focusing on the role of specific transcription factors that mediate the progression from NSCs to lineage-committed progenitors and, ultimately, the generation of mature neurons and glia.
Topics: Adult; Animals; Cell Survival; Dentate Gyrus; Gene Expression Regulation, Developmental; Humans; Mice; Neural Stem Cells; Neurogenesis; Transcription Factors; Transcription, Genetic
PubMed: 22588716
DOI: 10.1101/gad.187336.112 -
Nature Communications Aug 2020New neurons are generated in adult mammals. Adult hippocampal neurogenesis is considered to play an important role in cognition and mental health. The number and... (Review)
Review
New neurons are generated in adult mammals. Adult hippocampal neurogenesis is considered to play an important role in cognition and mental health. The number and properties of newly born neurons are regulatable by a broad range of physiological and pathological conditions. To begin to understand the underlying cellular mechanisms and functional relevance of adult neurogenesis, many studies rely on quantification of adult-born neurons. However, lack of standardized methods to quantify new neurons is impeding research reproducibility across laboratories. Here, we review the importance of stereology, and propose why and how it should be applied to the study of adult neurogenesis.
Topics: Adult; Adult Stem Cells; Animals; Brain; Dentate Gyrus; Humans; Models, Neurological; Neural Stem Cells; Neurogenesis; Neuronal Plasticity
PubMed: 32848155
DOI: 10.1038/s41467-020-18046-y -
The Journal of Neuroscience : the... Nov 2019The complementary processes of pattern completion and pattern separation are thought to be essential for successful memory storage and recall. The dentate gyrus (DG) and...
The complementary processes of pattern completion and pattern separation are thought to be essential for successful memory storage and recall. The dentate gyrus (DG) and proximal CA3 (pCA3) regions have been implicated in pattern separation, in part through extracellular recording studies of these areas. However, the DG contains two types of excitatory cells: granule cells of the granule layer and mossy cells of the hilus. Little is known about the firing properties of mossy cells in freely moving animals, and it is unclear how their activity may contribute to the mnemonic functions of the hippocampus. Furthermore, tetrodes in the dentate granule layer and pCA3 pyramidal layer can also record mossy cells, thus introducing ambiguity into the identification of cell types recorded. Using a random forests classifier, we classified cells recorded in DG (Neunuebel and Knierim, 2014) and pCA3 (Lee et al., 2015) of 16 male rats and separately examined the responses of granule cells, mossy cells, and pCA3 pyramidal cells in a local/global cue mismatch task. All three cell types displayed low correlations between the population representations of the rat's position in the standard and cue-mismatch sessions. These results suggest that all three excitatory cell types within the DG/pCA3 circuit may act as a single functional unit to support pattern separation. Mossy cells in the dentate gyrus (DG) are an integral component of the DG/pCA3 circuit. While the role of granule cells in the circuitry and computations of the hippocampus has been a focus of study for decades, the contributions of mossy cells have been largely overlooked. Recent studies have revealed the spatial firing properties of mossy cells in awake behaving animals, but how the activity of these highly active cells contributes to the mnemonic functions of the DG is uncertain. We separately analyzed mossy cells, granule cells, and pCA3 cells and found that all three cell types respond similarly to a local/global cue mismatch, suggesting that they form a single functional unit supporting pattern separation.
Topics: Animals; CA3 Region, Hippocampal; Dentate Gyrus; Male; Mossy Fibers, Hippocampal; Pyramidal Cells; Random Allocation; Rats; Rats, Long-Evans
PubMed: 31641051
DOI: 10.1523/JNEUROSCI.0940-19.2019 -
Molecular Brain Nov 2022The development, maturation, and plasticity of neural circuits are strongly influenced by experience and the interaction of an individual with their environment can have...
The development, maturation, and plasticity of neural circuits are strongly influenced by experience and the interaction of an individual with their environment can have a long-lasting effect on cognitive function. Using an enriched environment (EE) paradigm, we have recently demonstrated that enhancing social, physical, and sensory activity during the pre-weaning time in mice led to an increase of inhibitory and excitatory synapses in the dentate gyrus (DG) of the hippocampus. The structural plasticity induced by experience may affect information processing in the circuit. The DG performs pattern separation, a computation that enables the encoding of very similar and overlapping inputs into dissimilar outputs. In the presented study, we have tested the hypothesis that an EE in juvenile mice will affect DG's functions that are relevant for pattern separation: the decorrelation of the inputs from the entorhinal cortex (EC) and the recruitment of the principal excitatory granule cell (GC) during behavior. First, using a novel slice electrophysiology protocol, we found that the transformation of the incoming signal from the EC afferents by individual GC is moderately affected by EE. We further show that EE does not affect behaviorally induced recruitment of principal excitatory GC. Lastly, using the novel object recognition task, a hippocampus-dependent memory test, we show that the ontogeny of this discrimination task was similar among the EE mice and the controls. Taken together, our work demonstrates that pre-weaning enrichment moderately affects DG function.
Topics: Animals; Mice; Dentate Gyrus; Hippocampus; Entorhinal Cortex; Neurons; Synapses
PubMed: 36411441
DOI: 10.1186/s13041-022-00980-1