scholarly journals Potential implications of a monosynaptic pathway from mossy cells to adult-born granule cells of the dentate gyrus

2015 ◽  
Vol 9 ◽  
Author(s):  
Helen E. Scharfman ◽  
Hannah L. Bernstein
Keyword(s):  
Dentate Gyrus ◽  
Granule Cells ◽  
Mossy Cells

scholarly journals Spatial Representations of Granule Cells and Mossy Cells of the Dentate Gyrus

Neuron ◽  
2017 ◽  
Vol 93 (3) ◽  
pp. 677-690.e5 ◽  
Author(s):  
Douglas GoodSmith ◽  
Xiaojing Chen ◽  
Cheng Wang ◽  
Sang Hoon Kim ◽  
Hongjun Song ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Granule Cells ◽  
Spatial Representations ◽  
Mossy Cells

scholarly journals Bidirectional regulation of cognitive and anxiety-like behaviors by dentate gyrus mossy cells in male and female mice

2020 ◽  
Author(s):  
Justin J Botterill ◽  
K Yaragudri Vinod ◽  
Kathleen J Gerencer ◽  
Cátia M Teixeira ◽  
John J LaFrancois ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Cognitive Performance ◽  
Granule Cells ◽  
Gabaergic Neurons ◽  
Designer Drugs ◽  
Early Gene ◽  
Loss Of Function ◽  
Cell Type ◽  
Mossy Cells ◽  
Bidirectional Regulation

ABSTRACTThe dentate gyrus (DG) of the hippocampus is important for cognitive and affective behaviors. However, the circuits underlying these behaviors are unclear. DG mossy cells (MCs) have been a focus of attention because of their excitatory synapses on the primary DG cell type, granule cells (GCs). However, MCs also activate DG GABAergic neurons which inhibit GCs. We took advantage of specific methods and a gain- and loss-of function strategy with Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to study MCs in diverse behaviors. Using this approach, manipulations of MCs could bidirectionally regulate behavior. The results suggest that inhibiting MCs can reduce anxiety-like behavior and improve cognitive performance. However, not all cognitive or anxiety-related behaviors were influenced, suggesting specific roles of MCs in some but not all types of cognition and anxiety. Notably, several behaviors showed sex-specific effects, with females often showing more pronounced effects than the males. We also used the immediate early gene c-Fos to address whether DREADDs bidirectionally regulated MC or GC activity. We confirmed excitatory DREADDs increased MC c-Fos. However, there was no change in GC c-Fos, consistent with MC activation leading to GABAergic inhibition of GCs. In contrast, inhibitory DREADDs led to a large increase in GC c-Fos, consistent with a reduction in MC excitation of GABAergic neurons, and reduced inhibition of GCs. Taken together, these results suggest that MCs regulate anxiety and cognition in specific ways. We also raise the possibility that cognitive performance may be improved by reducing anxiety.SIGNIFICANCE STATEMENTThe dentate gyrus (DG) has many important cognitive roles as well as being associated with affective behavior. This study addressed how a glutamatergic DG cell type called mossy cells (MCs) contributes to diverse behaviors, which is timely because it is known that MCs regulate the activity of the primary DG cell type, granule cells (GCs), but how MC activity influences behavior is unclear. We show, surprisingly, that activating MCs can lead to adverse behavioral outcomes, and inhibiting MCs have an opposite effect. Importantly, the results appeared to be task-dependent and showed that testing both sexes was important. Additional experiments indicated what MC and GC circuitry was involved. Taken together, the results suggest how MCs influence behaviors that involve the DG.

scholarly journals Dentate Gyrus Mossy Cells Share a Role in Pattern Separation with Dentate Granule Cells and Proximal CA3 Pyramidal Cells

2019 ◽  
Vol 39 (48) ◽  
pp. 9570-9584 ◽  
Author(s):  
Douglas GoodSmith ◽  
Heekyung Lee ◽  
Joshua P. Neunuebel ◽  
Hongjun Song ◽  
James J. Knierim
Keyword(s):  
Dentate Gyrus ◽  
Granule Cells ◽  
Pyramidal Cells ◽  
Pattern Separation ◽  
Dentate Granule Cells ◽  
Mossy Cells ◽  
Ca3 Pyramidal Cells

Positive feedback from hilar mossy cells to granule cells in the dentate gyrus revealed by voltage-sensitive dye and microelectrode recording

1996 ◽  
Vol 76 (1) ◽  
pp. 601-616 ◽  
Author(s):  
M. B. Jackson ◽  
H. E. Scharfman
Keyword(s):  
Dentate Gyrus ◽  
Granule Cells ◽  
Excitatory Amino Acid ◽  
Molecular Layer ◽  
Perforant Path ◽  
Field Potentials ◽  
Microelectrode Recording ◽  
Mossy Cells ◽  
Dye Fluorescence ◽  
Site Of Stimulation

1. Microelectrode recording and fluorescence measurement with voltage-sensitive dyes were employed in horizontal hippocampal slices from rat to investigate responses in the dentate gyrus to molecular layer and hilar stimulation. 2. Both field potential and dye fluorescence measurement revealed that electrical stimulation of the molecular layer produced strong excitation throughout large regions of the dentate gyrus at considerable distances from the site of stimulation. 3. Treatment of slices with the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and (+/-)-2-amino-5-phosphonovaleric acid (APV) unmasked dye fluorescence signals in the outer and middle molecular layers corresponding to action potentials in axons, presumably belonging to the perforant path. The spread of these axonal signals away from the site of stimulation was far less extensive than the spread of control signals through the same regions before blockade of excitatory synapses. Large control responses could be seen in regions distant from the stimulation site where the axonal signals were not detectable. A lack of correlation between control signals and axonal signals revealed by DNQX and APV supports the hypothesis that responses in distal regions of the molecular layer were not dependent on perforant path axons. 4. The perforant path was cut by producing a lesion in the outer two-thirds of the molecular layer. Both dye fluorescence and microelectrode recording showed that stimulation on one side of the lesion could produce signals on the same side as well as across the lesion. The lesion did not block the spread of excitation through the molecular layer. Across the lesion from the site of stimulation, negative-going field potentials were observed to peak in the inner molecular layer, which is the major field of projection of hilar mossy cells. 5. Electrical stimulation in the hilus adjacent to the granule cell layer evoked dye fluorescence responses in the molecular layer. Stimulation at this site evoked negative-going field potentials that peaked in the inner molecular layer. These signals were sensitive to excitatory amino acid receptor antagonists but not to gamma-aminobutyric acid-A (GABAA) receptor antagonists. 6. Activation of excitatory amino acid receptors in the hilus by focal application of (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) elicited negative-going field potentials in the granule cell layer and depolarization of granule cells. Field potentials were blocked by tetrodotoxin (TTX), indicating that they were not caused by direct activation of receptors on granule cells, but rather by synapses from hilar neurons on granule cells. 7. These results taken together with previous studies of hilar mossy cells suggest a fundamental circuit consisting of granule cells exciting hilar mossy cells, which then excite more granule cells. This circuit provides positive feedback and can be considered a form of "recurrent excitation" unique to the dentate gyrus. The robustness of this circuit in hippocampal slices under control conditions suggest that mossy cell excitation of granule cells could play an important role in the normal activity of the hippocampus, and, when inhibition is compromised, this circuit could contribute to the generation and spread of seizures.

scholarly journals Excitatory effects of dentate gyrus mossy cells and their ability to influence granule cell firing: an optogenetic study in adult mouse hippocampal slices

2020 ◽  
Author(s):  
Hannah L. Bernstein ◽  
Yi-Ling Lu ◽  
Justin J. Botterill ◽  
Áine M. Duffy ◽  
John J. LaFrancois ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Granule Cells ◽  
Molecular Layer ◽  
Hippocampal Slices ◽  
Gabaergic Neurons ◽  
Excitatory Effect ◽  
Experimental Conditions ◽  
Mossy Cells ◽  
Direct Excitation ◽  
Cell Firing

ABSTRACTGlutamatergic dentate gyrus (DG) mossy cells (MCs) innervate the primary cell type, granule cells (GCs), and GABAergic neurons which inhibit GCs. Prior studies suggest that the net effect of MCs is mainly to inhibit GCs, leading one to question why direct excitation of GCs is often missed. We hypothesized that MCs do have excitatory effects, but each GC is only excited weakly, at least under most experimental conditions. To address this hypothesis, MC axons were stimulated optogenetically in slices. A brief optogenetic stimulus to MC axons in the inner molecular layer (IML) led to a short-latency field EPSP (fEPSP) in the IML, suggesting there was a direct excitatory effect on GCs. Population spikes were negligible however, consistent with weak excitation. FEPSPs reflected AMPA/NMDA receptor-mediated EPSPs in GCs. EPSPs reached threshold after GC depolarization or facilitating NMDA receptors. GABAA and GABAB receptor-mediated IPSPs often followed EPSPs. At the network level, an optogenetic stimulus led to a brief, small facilitation of the PP-evoked population spike followed by a longer, greater inhibition. These data are consistent with rapid and selective GC firing by MCs (MC → GC) and disynaptic inhibition (MC → GABAergic neuron → GC). Notably, optogenetic excitation was evoked for both dorsal and ventral MCs, ipsilateral and contralateral MC axons, and two Cre lines. Together the results suggest a way to reconcile past studies and provide new insight into the balance of excitation and inhibition of GCs by MCs.SIGNIFICANCE STATEMENTMossy cells (MCs) of the dentate gyrus (DG) are glutamatergic and innervate granule cells (GCs). The net effect of MCs has been debated because MCs also innervate GABAergic neurons which inhibit GCs. The results shown here suggest that MCs excite numerous GCs, but excitation is weak at GC resting potentials, and requires specific conditions to trigger GC APs. The results are consistent with a GC network that is designed for selective activation.

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

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Soyoun Kim ◽  
Dajung Jung ◽  
Sébastien Royer
Keyword(s):  
Dentate Gyrus ◽  
Spatial Information ◽  
Granule Cells ◽  
Place Cells ◽  
Competitive Learning ◽  
Spatial Representations ◽  
Mossy Cells ◽  
Object Locations ◽  
Treadmill Belt ◽  
The Continuum

Abstract Place cells exhibit spatially selective firing fields that collectively map the continuum of positions in environments; how such activity pattern develops with experience is largely unknown. Here, we record putative granule cells (GCs) and mossy cells (MCs) from the dentate gyrus (DG) over 27 days as mice repetitively run through a sequence of objects fixed onto a treadmill belt. We observe a progressive transformation of GC spatial representations, from a sparse encoding of object locations and spatial patterns to increasingly more single, evenly dispersed place fields, while MCs show little transformation and preferentially encode object locations. A competitive learning model of the DG reproduces GC transformations via the progressive integration of landmark-vector cells and spatial inputs and requires MC-mediated feedforward inhibition to evenly distribute GC representations, suggesting that GCs slowly encode conjunctions of objects and spatial information via competitive learning, while MCs help homogenize GC spatial representations.

scholarly journals Population and Individual Firing Behaviors in Sparsely Synchronized Rhythms in The Hippocampal Dentate Gyrus

2021 ◽  
Author(s):  
Sang-Yoon Kim ◽  
Woochang Lim
Keyword(s):  
Dentate Gyrus ◽  
Granule Cells ◽  
Phase Locking ◽  
Random Phase ◽  
Firing Activity ◽  
Hippocampal Dentate Gyrus ◽  
Population Frequency ◽  
Mossy Cells ◽  
Winner Take All ◽  
Take All

We investigate population and individual firing behaviors in sparsely synchronized rhythms (SSRs) in a spiking neural network of the hippocampal dentate gyrus (DG). The main encoding granule cells (GCs) are grouped into lamellar clusters. In each GC cluster, there is one inhibitory (I) basket cell (BC) along with excitatory (E) GCs, and they form the E-I loop. Winner-take-all competition, leading to sparse activation of the GCs, occurs in each GC cluster. Such sparsity has been thought to enhance pattern separation performed in the DG. During the winner-take-all competition, SSRs are found to appear in each population of the GCs and the BCs through interaction of excitation of the GCs with inhibition of the BCs. Sparsely synchronized spiking stripes appear successively with the population frequency fp (= 13 Hz) in the raster plots of spikes. We also note that excitatory hilar mossy cells (MCs) control the firing activity of the GC-BC loop by providing excitation to both the GCs and the BCs. SSR also appears in the population of MCs via interaction with the GCs (i.e., GC-MC loop). Population behaviors in the SSRs are quantitatively characterized in terms of the synchronization measures. In addition, we investigate individual firing activity of GCs, BCs, and MCs in the SSRs. Individual GCs exhibit random spike skipping, leading to a multi-peaked inter-spike-interval histogram, which is well characterized in terms of the random phase-locking degree. In this case, population-averaged mean-firing-rate (MFR) <fi(GC)> is less than the population frequency fp. On the other hand, both BCs and MCs show "intrastripe" burstings within stripes, together with "interstripe" random spike skipping. Thus, the population-averaged MFR <fi(X)> (X= MC and BC) is larger than fp, in contrast to the case of the GCs. MC loss may occur during epileptogenesis. With decreasing the fraction of the MCs, changes in the population and individual firings in the SSRs are also studied. Finally, quantitative association between the population/individual firing behaviors in the SSRs and the winner-take-all competition is discussed.

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