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Epilepsia Jun 2008Status epilepticus (SE) not only results in an increased number of newly generated neurons in the dentate gyrus but also leads to structural alterations of many of these... (Review)
Review
Status epilepticus (SE) not only results in an increased number of newly generated neurons in the dentate gyrus but also leads to structural alterations of many of these newborn granule cells. One of the structural changes involving newly generated dentate granule cells is the formation of hilar basal dendrites that persist on mature granule cells and integrate into synaptic circuitry. SE also causes other newborn granule cells to migrate ectopically into the hilus, and these cells also integrate into synaptic circuitry. This article will describe these structural alterations of granule cells found in the dentate gyrus after SE and will also discuss the time course of these events and possible underlying causes.
Topics: Adult Stem Cells; Animals; Dentate Gyrus; Humans; Neurons; Status Epilepticus
PubMed: 18522596
DOI: 10.1111/j.1528-1167.2008.01633.x -
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 -
Seizure Jan 2008Status epilepticus may cause long-term functional and structural consequences possibly resulting in brain dysfunctions such as chronic epilepsy. In epileptogenesis, the...
Status epilepticus may cause long-term functional and structural consequences possibly resulting in brain dysfunctions such as chronic epilepsy. In epileptogenesis, the dentate gyrus plays a key role in regulating the excitability of highly vulnerable and potentially epileptogenic downstream structures in the hippocampus proper. One, four and eight weeks after electrically induced status epilepticus, excitability and neuronal degeneration in the rat dentate gyrus were examined with intracerebral electrodes and Fluoro Jade (FJ) staining, respectively. Half of the animals had developed chronic epilepsy by 8 weeks after status epilepticus. Sham-operated controls did not exhibit seizures, and the excitatory parameters remained unchanged. Compared to controls, 8 weeks after status epilepticus the population spike latency in the dentate gyrus was significantly reduced (p<0.05) and substantial neuronal degeneration was seen (p<0.05). In summary, status epilepticus results in functional and morphological alterations in the dentate gyrus likely contributing to epileptogenesis.
Topics: Animals; Chronic Disease; Data Interpretation, Statistical; Dentate Gyrus; Electric Stimulation; Electrodes, Implanted; Excitatory Postsynaptic Potentials; Fluoresceins; Fluorescent Dyes; Male; Neurons; Organic Chemicals; Rats; Status Epilepticus; Videotape Recording
PubMed: 17728157
DOI: 10.1016/j.seizure.2007.07.008 -
Epilepsy Research Aug 2023Epileptogenesis is a complex process involving a multitude of changes at the molecular, cellular and network level. Previous studies have identified several key...
Epileptogenesis is a complex process involving a multitude of changes at the molecular, cellular and network level. Previous studies have identified several key alterations contributing to epileptogenesis and the development of hyper-excitability in different animal models, but only a few have focused on the early stages of this process. For post status epilepticus (SE) temporal lobe epilepsy in particular, understanding network dynamics during the early phases might be crucial for developing accurate preventive treatments to block the development of chronic spontaneous seizures. In this study, we used a viral vector mediated approach to examine activity of neurons in the dentate gyrus of the hippocampus during early epileptogenesis. We find that while granule cells are active 8 h after SE and then gradually decrease their activity, Calretinin-positive mossy cells and Neuropeptide Y-positive GABAergic interneurons in the hilus show a delayed activation pattern starting at 24 and peaking at 48 h after SE. These data suggest that indirect inhibition of granule cells by mossy cells through recruitment of local GABAergic interneurons could be an important mechanisms of excitability control during early epileptogenesis, and contribute to our understanding of the complex role of these cells in normal and pathological conditions.
Topics: Animals; Neurons; Hippocampus; Seizures; Interneurons; Epilepsy, Temporal Lobe; Status Epilepticus; Dentate Gyrus; Disease Models, Animal
PubMed: 37364343
DOI: 10.1016/j.eplepsyres.2023.107182 -
Cell and Tissue Research Sep 2018Hilar mossy cells (MCs) of the dentate gyrus (DG) distinguish the DG from other hippocampal subfields (CA1-3) because there are two glutamatergic cell types in the DG... (Review)
Review
Hilar mossy cells (MCs) of the dentate gyrus (DG) distinguish the DG from other hippocampal subfields (CA1-3) because there are two glutamatergic cell types in the DG rather than one. Thus, in the DG, the main cell types include glutamatergic granule cells (GCs) and MCs, whereas in CA1-3, the only glutamatergic cell type is the pyramidal cell. In contrast to GCs, MCs are different in morphology, intrinsic electrophysiological properties, afferent input and axonal projections, so their function is likely to be very different from GCs. Why are MCs necessary to the DG? In past studies, the answer has been unclear because MCs not only excite GCs directly but also inhibit them disynaptically, by exciting GABAergic neurons that project to GCs. Results of new studies are discussed that shed light on this issue. These studies take advantage of recently available transgenic mice with Cre recombinase expression mostly in MCs and techniques such as optogenetics and DREADDs (designer receptors exclusively activated by designer drugs). The recent studies also address in vivo behavioral functions of MCs. Some of the results support past hypotheses whereas others suggest new conceptualizations of how the MCs contribute to DG circuitry and function. While substantial progess has been made, additional research is still needed to clarify the characteristics and functions of these unique cells.
Topics: Animals; Behavior; Computer Simulation; Dentate Gyrus; Electrophysiological Phenomena; GABAergic Neurons; Integrases; Mice; Mice, Transgenic; Models, Neurological; Mossy Fibers, Hippocampal; Optogenetics; Rats
PubMed: 29222692
DOI: 10.1007/s00441-017-2750-5 -
Brain Structure & Function Sep 2017The molecular layer of the dentate gyrus and the anatomically adjacent stratum lacunosum-moleculare of CA1 area, represent afferent areas at distinct levels of the...
The molecular layer of the dentate gyrus and the anatomically adjacent stratum lacunosum-moleculare of CA1 area, represent afferent areas at distinct levels of the hippocampal trisynaptic loop. Afferents to the dentate gyrus and CA1 area originate from different cell populations, including projection cells in entorhinal cortex layers two and three, respectively. To determine the organization of oscillatory activities along these terminal fields, we recorded local field potentials from multiple sites in the dentate gyrus and CA1 area of the awake mice, and localized gamma frequency (30-150 Hz) oscillations in different layers by means of current source density analysis. During theta oscillations, we observed different temporal and spectral organization of gamma oscillations in the dendritic layers of the dentate gyrus and CA1 area, with a sharp transition across the hippocampal fissure. In CA1 stratum lacunosum-moleculare, transient mid-frequency gamma oscillations (CA1-gamma; 80 Hz) occurred on theta cycle peaks, while in the dentate gyrus, fast (DG-gamma; 110 Hz), and slow (DG-gamma; 40 Hz) gamma oscillations preferentially occurred on troughs of theta waves. Units in dentate gyrus, in contrast to units in CA1 pyramidal layer, phase-coupled to DG-gamma, which was largely independent from CA1 fast gamma oscillations (CA1-gamma) of similar frequency and timing. Spike timing of units recorded in either CA1 area or dentate gyrus were modulated by CA1-gamma. Our experiments disclosed a set of gamma oscillations that differentially regulate neuronal activity in the dentate gyrus and CA1 area, and may allow flexible segregation and integration of information across different levels of hippocampal circuitry.
Topics: Action Potentials; Animals; Biological Clocks; CA1 Region, Hippocampal; Dendrites; Dentate Gyrus; Electrodes; Gamma Rhythm; Male; Mice; Mice, Inbred C57BL; Nerve Net; Spectrum Analysis; Wakefulness
PubMed: 28391402
DOI: 10.1007/s00429-017-1421-3 -
Journal of Neurophysiology Mar 2000We have investigated the propagation of epileptiform discharges induced by 4-aminopyridine (4-AP, 50 microM) in adult mouse hippocampus-entorhinal cortex slices, before...
We have investigated the propagation of epileptiform discharges induced by 4-aminopyridine (4-AP, 50 microM) in adult mouse hippocampus-entorhinal cortex slices, before and after Schaffer collateral cut. 4-AP application induced 1) ictal epileptiform activity that disappeared over time and 2) interictal epileptiform discharges, which continued throughout the experiment. Using simultaneous field potential and [K(+)](o) recordings, we found that entorhinal and dentate ictal epileptiform discharges were accompanied by comparable elevations in [K(+)](o) (up to 12 mM from a baseline value of 3.2 mM), whereas smaller rises in [K(+)](o) (up to 6 mM) were associated with ictal activity in CA3. Cutting the Schaffer collaterals disclosed the occurrence of ictal discharges that were associated with larger rises in [K(+)](o) as compared with the intact slice. Further lesion of the perforant path blocked ictal activity and the associated [K(+)](o) increases in the dentate gyrus, indicating synaptic propagation to this area. Time delay measurements demonstrated that ictal epileptiform activity in the intact hippocampal-entorhinal cortex slice propagated via the trisynaptic path. However, after Schaffer collateral cut, ictal discharges continued to occur in CA1 and subiculum and spread to these areas directly from the entorhinal cortex. Thus our data indicate that the increased epileptogenicity of the dentate gyrus (a prominent feature of temporal lobe epilepsy as well), may depend on perforant path propagation of entorhinal ictal discharges, irrespective of mossy fiber reorganization. Moreover, hippocampal neuronal damage that is acutely mimicked in our model by Schaffer collateral cut, may contribute to "short-circuit" propagation of activity by pathways that are masked when the hippocampus is intact.
Topics: 4-Aminopyridine; Animals; Dentate Gyrus; Electrophysiology; Entorhinal Cortex; Epilepsy; Evoked Potentials; In Vitro Techniques; Male; Mice; Mice, Inbred BALB C; Microelectrodes; Mossy Fibers, Hippocampal; Neural Pathways; Potassium; Seizures; Synapses
PubMed: 10712442
DOI: 10.1152/jn.2000.83.3.1115 -
ELife Jan 2017Adult-born neurons are continually produced in the dentate gyrus but it is unclear whether synaptic integration of new neurons affects the pre-existing circuit. Here we...
Adult-born neurons are continually produced in the dentate gyrus but it is unclear whether synaptic integration of new neurons affects the pre-existing circuit. Here we investigated how manipulating neurogenesis in adult mice alters excitatory synaptic transmission to mature dentate neurons. Enhancing neurogenesis by conditional deletion of the pro-apoptotic gene in stem cells reduced excitatory postsynaptic currents (EPSCs) and spine density in mature neurons, whereas genetic ablation of neurogenesis increased EPSCs in mature neurons. Unexpectedly, we found that deletion in developing and mature dentate neurons increased EPSCs and prevented neurogenesis-induced synaptic suppression. Together these results show that neurogenesis modifies synaptic transmission to mature neurons in a manner consistent with a redistribution of pre-existing synapses to newly integrating neurons and that a non-apoptotic function of the Bax signaling pathway contributes to ongoing synaptic refinement within the dentate circuit.
Topics: Animals; Dentate Gyrus; Excitatory Postsynaptic Potentials; Mice; Nerve Net; Neurogenesis; Neurons; Synaptic Transmission
PubMed: 28135190
DOI: 10.7554/eLife.19886 -
Journal of Neurophysiology Feb 2020The dentate gyrus (DG), the input gate to the hippocampus proper, is anatomically segregated into three different sectors, namely, the suprapyramidal blade, the crest...
The dentate gyrus (DG), the input gate to the hippocampus proper, is anatomically segregated into three different sectors, namely, the suprapyramidal blade, the crest region, and the infrapyramidal blade. Although there are well-established differences between these sectors in terms of neuronal morphology, connectivity patterns, and activity levels, differences in electrophysiological properties of granule cells within these sectors have remained unexplored. Here, employing somatic whole cell patch-clamp recordings from the rat DG, we demonstrate that granule cells in these sectors manifest considerable heterogeneities in their intrinsic excitability, temporal summation, action potential characteristics, and frequency-dependent response properties. Across sectors, these neurons showed positive temporal summation of their responses to inputs mimicking excitatory postsynaptic currents and showed little to no sag in their voltage responses to pulse currents. Consistently, the impedance amplitude profile manifested low-pass characteristics and the impedance phase profile lacked positive phase values at all measured frequencies and voltages and for all sectors. Granule cells in all sectors exhibited class I excitability, with broadly linear firing rate profiles, and granule cells in the crest region fired significantly fewer action potentials compared with those in the infrapyramidal blade. Finally, we found weak pairwise correlations across the 18 different measurements obtained individually from each of the three sectors, providing evidence that these measurements are indeed reporting distinct aspects of neuronal physiology. Together, our analyses show that granule cells act as integrators of afferent information and emphasize the need to account for the considerable physiological heterogeneities in assessing their roles in information encoding and processing. We employed whole cell patch-clamp recordings from granule cells in the three subregions of the rat dentate gyrus to demonstrate considerable heterogeneities in their intrinsic excitability, temporal summation, action potential characteristics, and frequency-dependent response properties. Across sectors, granule cells did not express membrane potential resonance, and their impedance profiles lacked inductive phase leads at all measured frequencies. Our analyses also show that granule cells manifest class I excitability characteristics, categorizing them as integrators of afferent information.
Topics: Animals; Dentate Gyrus; Electrophysiological Phenomena; Male; Neurons; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley
PubMed: 31913748
DOI: 10.1152/jn.00443.2019 -
Journal of Rehabilitation Medicine May 2003Recent findings concerning the regenerative potential of the adult brain suggest a more pronounced plasticity than previously thought. One such finding is the generation... (Review)
Review
Recent findings concerning the regenerative potential of the adult brain suggest a more pronounced plasticity than previously thought. One such finding is the generation of new neurons in the adult brain (neurogenesis). Loss of neurons has long been considered to be irreversible in the adult human brain, i.e., dead neurons are not replaced. The inability to generate replacement cells is thought to be an important cause of neurological disease and impairment. In most brain regions, the generation of neurons is generally confined to a discrete developmental period. Exceptions have recently been described in several regions of the brain that have been shown to generate new neurons well into the postnatal and adult period. One of the best characterized regions is the subgranular zone of the dentate gyrus in the brain, where granule neurons are generated throughout life from a population of progenitor/ stem cells. Furthermore, recent findings suggest that neurogenesis may be of importance for memory function as well as mood disorders. Several very important questions can be formulated on the basis of these discoveries, for instance, what factors influence the generation of new neurons and whether it is possible for enhanced neurogenesis to contribute to functional recovery.
Topics: Adult; Animals; Cell Division; Dentate Gyrus; Environment; Humans; Infant, Newborn; Nerve Regeneration; Neuronal Plasticity; Rats; Stem Cell Transplantation; Stem Cells
PubMed: 12817652
DOI: 10.1080/16501960310010098