scholarly journals Adult‐born granule cell mossy fibers preferentially target parvalbumin‐positive interneurons surrounded by perineuronal nets

Hippocampus ◽  
2021 ◽  
Author(s):  
Brandy A. Briones ◽  
Thomas J. Pisano ◽  
Miah N. Pitcher ◽  
Amanda E. Haye ◽  
Emma J. Diethorn ◽  
...  
Keyword(s):  
Granule Cell ◽  
Mossy Fibers ◽  
Perineuronal Nets

Epilepsy induced collateral sprouting of hippocampal mossy fibers: Does it induce the development of ectopic synapses with granule cell dendrites?

Hippocampus ◽  
1993 ◽  
Vol 3 (3) ◽  
pp. 257-268 ◽  
Author(s):  
Alfonso Represa ◽  
Isabel Jorquera ◽  
Gildas le gal la Salle ◽  
Yehezkel Ben-Ari
Keyword(s):  
Granule Cell ◽  
Mossy Fibers ◽  
Collateral Sprouting

Optical Recording Study of Granule Cell Activities in the Hippocampal Dentate Gyrus of Kainate-Treated Rats

2000 ◽  
Vol 83 (4) ◽  
pp. 2421-2430 ◽  
Author(s):  
Yo Otsu ◽  
Eiichi Maru ◽  
Hisayuki Ohata ◽  
Ichiro Takashima ◽  
Riichi Kajiwara ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Granule Cell ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Molecular Layer ◽  
Mossy Fibers ◽  
Optical Recording ◽  
Granule Cell Layer ◽  
Gabaergic Inhibition ◽  
Mossy Fiber Sprouting

In the epileptic hippocampus, newly sprouted mossy fibers are considered to form recurrent excitatory connections to granule cells in the dentate gyrus and thereby increase seizure susceptibility. To study the effects of mossy fiber sprouting on neural activity in individual lamellae of the dentate gyrus, we used high-speed optical recording to record signals from voltage-sensitive dye in hippocampal slices prepared from kainate-treated epileptic rats (KA rats). In 14 of 24 slices from KA rats, hilar stimulation evoked a large depolarization in almost the entire molecular layer in which granule cell apical dendrites are located. The signals were identified as postsynaptic responses because of their dependence on extracellular Ca2+. The depolarization amplitude was largest in the inner molecular layer (the target area of sprouted mossy fibers) and declined with increasing distance from the granule cell layer. In the inner molecular layer, a good correlation was obtained between depolarization size and the density of mossy fiber terminals detected by Timm staining methods. Blockade of GABAergic inhibition by bicuculline enlarged the depolarization in granule cell dendrites. Our data indicate that mossy fiber sprouting results in a large and prolonged synaptic depolarization in an extensive dendritic area and that the enhanced GABAergic inhibition partly masks the synaptic depolarization. However, despite the large dendritic excitation induced by the sprouted mossy fibers, seizurelike activity of granule cells was never observed, even when GABAergic inhibition was blocked. Therefore, mossy fiber sprouting may not play a critical role in epileptogenesis.

scholarly journals Dietary restriction reduces hippocampal neurogenesis and granule cell neuron density without affecting the density of mossy fibers

2017 ◽  
Vol 1663 ◽  
pp. 59-65 ◽  
Author(s):  
Miranda C. Staples ◽  
McKenzie J. Fannon ◽  
Karthik K. Mysore ◽  
Rahul R. Dutta ◽  
Alexandria T. Ongjoco ◽  
...  
Keyword(s):  
Dietary Restriction ◽  
Granule Cell ◽  
Mossy Fibers ◽  
Hippocampal Neurogenesis ◽  
Neuron Density

Multiple Erythroid Ankyrin Isoforms in the Mouse Cerebellum: Differential Localization in Purkinje Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1725-1725
Author(s):  
Connie B. Birkenmeier ◽  
Timothy H. Young ◽  
Jane E. Barker ◽  
Luanne L. Peters
Keyword(s):  
Axonal Transport ◽  
Purkinje Cells ◽  
Granule Cell ◽  
Mossy Fiber ◽  
Mossy Fibers ◽  
Granule Cell Layer ◽  
Specific Marker ◽  
Functional Link ◽  
Mouse Cerebellum ◽  
And Function

Abstract The erythroid ankyrin gene (Ank1) produces a large and varied number of isoforms due to alternative splicing of the mRNA. In addition to expression in erythroid tissues, some of these Ank1 proteins are highly expressed in the Purkinje cells (PKC) of the mouse cerebellum. Mice deficient in Ank1 as a result of a mutation in the Ank1 gene (normoblastosis, nb) show a progressive loss of PKCs with an attendant ataxia. We have generated a panel of Ank1 antibodies to aid in sorting out the expression pattern and function of Ank1 proteins in the cerebellum. Two of these antibodies are specific to the alternatively spliced A and B COOH-terminal segments of Ank1. Immunohistochemical (IHC) experiments using these antibodies show strikingly different patterns of localization. Anti-C-termA (α-A) stains the PKC cell body and dendrites while anti-C-termB (α-B) is restricted to the PKC membrane. Both antibodies stain structures in the granule cell layer (GCL) including the granule cell membrane (α-B) and structures known as glomeruli where granule cell dendrites synapse with mossy fiber axons (α-A and α-B). Mossy fibers are a major afferent system that inputs to the cerebellum. α-A, α-B, antibodies to the α-1 subunit of Na+/K+ATPase (NaK-α1) and anti-Synapsin 1, a specific marker for synaptic vesicles, all co-localize in the glomeruli, suggesting a possible functional link. PKC membrane staining with α-B is absent in nb/nb cerebellum whereas PKC staining with α-A is unaffected. GCL staining with both antibodies is reduced in the mutant and this deficit may be important to PKC survival since granule cell axons are a major input system to PKC dendrites. Immunoblots stained with α-A and α-B are consistent with the IHC findings. In addition to the typical large isoforms (∼210kD) that are deficient in the nb mutant, immunoblots of cerebellar lysates reveal a number of small Ank1 related proteins ranging in size from 17 to 50 kD. The α-A and α-B banding patterns are unaffected by the nb mutation suggesting that they may be produced by splicing out the exon containing the nb mutation (E36) or by using an alternative promoter in the 3′ end of the gene as was found for the small Ank1 isoforms in skeletal muscle. Additional IHC findings using GFP-tagged PKC show a PKC axonopathy in nb/nb cerebellum. PKC axons exhibit multiple swellings that accumulate with age raising the possibility that axonal transport is abnormal in the nb PKCs. In summary 1) immunoblots reveal multiple previously undescribed small Ank1 isoforms in cerebellum, 2) two of the alternate Ank1 COOH-termini show very different localization in PKC suggesting distinct functions for the Ank1 proteins carrying them, 3) in the GCL, antibodies to the two COOH-termini co-localize with antibodies to the Na+/K+ATPase α-1 subunit in synaptic densities, 4) deficiencies of Ank1 in the GCL of nb/nb mice may influence PKC survival and 5) axonal transport may be affected in nb/nb PKC. These findings indicate that Ank1 proteins play a more varied role in the cerebellum than previously suspected and suggest new directions for the study of Ank1 function.

scholarly journals Recruitment of an inhibitory hippocampal network after bursting in a single granule cell

2007 ◽  
Vol 104 (18) ◽  
pp. 7640-7645 ◽  
Author(s):  
Masahiro Mori ◽  
Beat H. Gähwiler ◽  
Urs Gerber
Keyword(s):  
Pyramidal Cell ◽  
Granule Cell ◽  
Mossy Fiber ◽  
Mossy Fibers ◽  
Pyramidal Cells ◽  
Network Activity ◽  
Inhibitory Input ◽  
Inhibitory Interneurons ◽  
Failure Rates ◽  
Ca3 Pyramidal Cells

The hippocampal CA3 area, an associational network implicated in memory function, receives monosynaptic excitatory as well as disynaptic inhibitory input through the mossy-fiber axons of the dentate granule cells. Synapses made by mossy fibers exhibit low release probability, resulting in high failure rates at resting discharge frequencies of 0.1 Hz. In recordings from functionally connected pairs of neurons, burst firing of a granule cell increased the probability of glutamate release onto both CA3 pyramidal cells and inhibitory interneurons, such that subsequent low-frequency stimulation evoked biphasic excitatory/inhibitory responses in a CA3 pyramidal cell, an effect lasting for minutes. Analysis of the unitary connections in the circuit revealed that granule cell bursting caused powerful activation of an inhibitory network, thereby transiently suppressing excitatory input to CA3 pyramidal cells. This phenomenon reflects the high incidence of spike-to-spike transmission at granule cell to interneuron synapses, the numerically much greater targeting by mossy fibers of inhibitory interneurons versus principal cells, and the extensively divergent output of interneurons targeting CA3 pyramidal cells. Thus, mossy-fiber input to CA3 pyramidal cells appears to function in three distinct modes: a resting mode, in which synaptic transmission is ineffectual because of high failure rates; a bursting mode, in which excitation predominates; and a postbursting mode, in which inhibitory input to the CA3 pyramidal cells is greatly enhanced. A mechanism allowing the transient recruitment of inhibitory input may be important for controlling network activity in the highly interconnected CA3 pyramidal cell region.

scholarly journals Contributions of Mossy Fiber and CA1 Pyramidal Cell Sprouting to Dentate Granule Cell Hyperexcitability in Kainic Acid–Treated Hippocampal Slice Cultures

2004 ◽  
Vol 92 (6) ◽  
pp. 3582-3595 ◽  
Author(s):  
Suzanne B. Bausch ◽  
James O. McNamara
Keyword(s):  
Dentate Gyrus ◽  
Kainic Acid ◽  
Granule Cell ◽  
Hippocampal Slice ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Mossy Fibers ◽  
Axonal Sprouting ◽  
Mossy Fiber Sprouting ◽  
Hippocampal Slice Cultures

Axonal sprouting like that of the mossy fibers is commonly associated with temporal lobe epilepsy, but its significance remains uncertain. To investigate the functional consequences of sprouting of mossy fibers and alternative pathways, kainic acid (KA) was used to induce robust mossy fiber sprouting in hippocampal slice cultures. Physiological comparisons documented many similarities in granule cell responses between KA- and vehicle-treated cultures, including: seizures, epileptiform bursts, and spontaneous excitatoty postsynaptic currents (sEPSCs) >600pA. GABAergic control and contribution of glutamatergic synaptic transmission were similar. Analyses of neurobiotin-filled CA1 pyramidal cells revealed robust axonal sprouting in both vehicle- and KA-treated cultures, which was significantly greater in KA-treated cultures. Hilar stimulation evoked an antidromic population spike followed by variable numbers of postsynaptic potentials (PSPs) and population spikes in both vehicle- and KA-treated cultures. Despite robust mossy fiber sprouting, knife cuts separating CA1 from dentate gyrus virtually abolished EPSPs evoked by hilar stimulation in KA-treated but not vehicle-treated cultures, suggesting a pivotal role of functional afferents from CA1 to dentate gyrus in KA-treated cultures. Together, these findings demonstrate striking hyperexcitability of dentate granule cells in long-term hippocampal slice cultures after treatment with either vehicle or KA. The contribution to hilar-evoked hyperexcitability of granule cells by the unexpected axonal projection from CA1 to dentate in KA-treated cultures reinforces the idea that axonal sprouting may contribute to pathologic hyperexcitability of granule cells.

Modest Increase in Extracellular Potassium Unmasks Effect of Recurrent Mossy Fiber Growth

2000 ◽  
Vol 84 (5) ◽  
pp. 2380-2389 ◽  
Author(s):  
Jeremy L. Hardison ◽  
Maxine M. Okazaki ◽  
J. Victor Nadler
Keyword(s):  
Granule Cell ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Epileptiform Activity ◽  
Mossy Fibers ◽  
Fiber Growth ◽  
Antidromic Stimulation ◽  
Frequency Facilitation ◽  
Mossy Fiber Pathway ◽  
Stimulation Of

The recurrent mossy fiber pathway of the dentate gyrus expands dramatically in many persons with temporal lobe epilepsy. The new connections among granule cells provide a novel mechanism of synchronization that could enhance the participation of these cells in seizures. Despite the presence of robust recurrent mossy fiber growth, orthodromic or antidromic activation of granule cells usually does not evoke repetitive discharge. This study tested the ability of modestly elevated [K+]o, reduced GABAA receptor-mediated inhibition and frequency facilitation to unmask the effect of recurrent excitation. Transverse slices of the caudal hippocampal formation were prepared from pilocarpine-treated rats that either had or had not developed status epilepticus with subsequent recurrent mossy fiber growth. During superfusion with standard medium (3.5 mM K+), antidromic stimulation of the mossy fibers evoked epileptiform activity in 14% of slices with recurrent mossy fiber growth. This value increased to ∼50% when [K+]o was raised to either 4.75 or 6 mM. Addition of bicuculline (3 or 30 μM) to the superfusion medium did not enhance the probability of evoking epileptiform activity but did increase the magnitude of epileptiform discharge if such activity was already present. (2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine (1 μM), which selectively activates type II metabotropic glutamate receptors present on mossy fiber terminals, strongly depressed epileptiform responses. This result implies a critical role for the recurrent mossy fiber pathway. No enhancement of the epileptiform discharge occurred during repetitive antidromic stimulation at frequencies of 0.2, 1, or 10 Hz. In fact, antidromically evoked epileptiform activity became progressively attenuated during a 10-Hz train. Antidromic stimulation of the mossy fibers never evoked epileptiform activity in slices from control rats under any condition tested. These results indicate that even modest changes in [K+]o dramatically affect granule cell epileptiform activity supported by the recurrent mossy fiber pathway. A small increase in [K+]o reduces the amount of recurrent mossy fiber growth required to synchronize granule cell discharge. Block of GABAA receptor-mediated inhibition is less efficacious and frequency facilitation may not be a significant factor.

scholarly journals The RacGAP βChimaerin is essential for cerebellar granule cell migration

2017 ◽  
Author(s):  
Jason A. Estep ◽  
Wenny Wong ◽  
Yiu-Cheung E. Wong ◽  
Brian M. Loui ◽  
Martin M. Riccomagno
Keyword(s):  
Granule Cell ◽  
Granule Cells ◽  
Cell Layer ◽  
Outer Part ◽  
Mossy Fibers ◽  
Small Population ◽  
Cerebellar Granule Cell ◽  
Granule Cell Layer ◽  
Radial Migration ◽  
Cerebellar Granule

AbstractDuring mammalian cerebellar development, postnatal granule cell progenitors proliferate in the outer part of the External Granule Layer (EGL). Postmitotic granule progenitors migrate tangentially in the inner EGL before switching to migrate radially inward, past the Purkinje cell layer, to achieve their final position in the mature Granule Cell Layer (GCL). Here, we show that the RacGAP β-chimaerin is expressed by a small population of late-born, premigratory granule cells. β-chimaerin deficiency causes a subset of granule cells to become arrested in the EGL, where they differentiate and form ectopic neuronal clusters. These clusters of granule cells are able to recruit aberrantly projecting mossy fibers. Collectively, these data suggest a role for β-chimaerin as an intracellular mediator of Cerebellar Granule Cell radial migration.

scholarly journals Morphological constraints on cerebellar granule cell combinatorial diversity

2017 ◽  
Author(s):  
Jesse I. Gilmer ◽  
Abigail L. Person
Keyword(s):  
Granule Cell ◽  
Granule Cells ◽  
Cell Layer ◽  
Mossy Fiber ◽  
Mossy Fibers ◽  
Cerebellar Granule Cell ◽  
Granule Cell Layer ◽  
Information Encoding ◽  
Cerebellar Granule ◽  
Local Sampling

AbstractCombinatorial expansion by the cerebellar granule cell layer (GCL) is fundamental to theories of cerebellar contributions to motor control and learning. Granule cells sample approximately four mossy fiber inputs and are thought to form a combinatorial code useful for pattern separation and learning. We constructed a spatially realistic model of the cerebellar granule cell layer and examined how GCL architecture contributes to granule cell (GrC) combinatorial diversity. We found that GrC combinatorial diversity saturates quickly as mossy fiber input diversity increases, and that this saturation is in part a consequence of short dendrites, which limit access to diverse inputs and favor dense sampling of local inputs. This local sampling also produced GrCs that were combinatorially redundant, even when input diversity was extremely high. In addition, we found that mossy fibers clustering, which is a common anatomical pattern, also led to increased redundancy of GrC input combinations. We related this redundancy to hypothesized roles of temporal expansion of GrC information encoding in service of learned timing, and show that GCL architecture produces GrC populations that support both temporal and combinatorial expansion. Finally, we used novel anatomical measurements from mice of either sex to inform modeling of sparse and filopodia-bearing mossy fibers, finding that these circuit features uniquely contribute to enhancing GrC diversification and redundancy. Our results complement information theoretic studies of granule layer structure and provide insight into the contributions of granule layer anatomical features to afferent mixing.Significance StatementCerebellar granule cells are among the simplest neurons, with tiny somata and on average just four dendrites. These characteristics, along with their dense organization, inspired influential theoretical work on the granule cell layer (GCL) as a combinatorial expander, where each granule cell represents a unique combination of inputs. Despite the centrality of these theories to cerebellar physiology, the degree of expansion supported by anatomically realistic patterns of inputs is unknown. Using modeling and anatomy, we show that realistic input patterns constrain combinatorial diversity by producing redundant combinations, which nevertheless could support temporal diversification of like-combinations, suitable for learned timing. Our study suggests a neural substrate for producing high levels of both combinatorial and temporal diversity in the GCL.

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