Early appearance of developmental alterations in the dendritic tree of the hippocampal granule cells in the Ts65Dn model of Down syndrome

Hippocampus ◽  
2021 ◽  
Author(s):  
Beatrice Uguagliati ◽  
Abdel‐Rahman Al‐Absi ◽  
Fiorenza Stagni ◽  
Marco Emili ◽  
Andrea Giacomini ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Granule Cells ◽  
Dendritic Tree ◽  
Early Appearance

Membrane properties of dentate gyrus granule cells: comparison of sharp microelectrode and whole-cell recordings

1992 ◽  
Vol 67 (5) ◽  
pp. 1346-1358 ◽  
Author(s):  
K. J. Staley ◽  
T. S. Otis ◽  
I. Mody
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Dentate Gyrus ◽  
Granule Cells ◽  
Dendritic Tree ◽  
Membrane Voltage ◽  
Membrane Properties ◽  
Whole Cell ◽  
Calcium Buffers ◽  
Whole Cell Recordings

1. Whole-cell and sharp electrode recordings from adult rat dentate gyrus GCs were performed in the 400-microns-thick hippocampal slice preparation maintained at 34 +/- 1 degrees C. Intrinsic membrane properties of granule cells (GCs) were evaluated with the use of a switching current-clamp amplifier. 2. With the whole-cell technique, the average resting membrane potential (RMP) of GCs was -85 mV when a potassium gluconate electrode solution was used versus -74 mV measured with potassium acetate-filled sharp microelectrodes. The membrane voltage response to injected current was linear over two membrane potential ranges, greater than 10 mV hyperpolarized from RMP and between 10 mV more negative than RMP and -62 mV. The average input resistances (RN) calculated over these ranges were 107 and 228 M omega in the whole-cell recordings versus 37 and 54 M omega in the sharp electrode recordings. There was no correlation between RMP and RN with either recording technique. The membrane time constant (tau m) determined at the RMP was 26.9 ms for whole-cell recordings and 13.9 ms for sharp electrode recordings. 3. There was no evidence of time-dependent changes in RMP, RN, and tau m in whole-cell recordings, although the slow inward rectification seen at hyperpolarized potentials decreased over 30-60 min. Addition of calcium buffers to the whole-cell recording solution did not result in a significant change in the average RMP, the average RN, or the average tau m. 4. Action potential threshold was comparable in whole-cell (-49 mV) and sharp electrode (-52 mV) recordings, but action potential amplitude was larger in whole-cell (126 mV) than in sharp electrode (106 mV) recordings. Spike frequency adaptation was present in the whole-cell recordings and could be abolished by addition of calcium buffers to the electrode solution. 5. We estimated rho, the ratio of dendritic to somatic conductance, to be 5.1 for the whole-cell records and 2.1 for sharp electrode recordings. The electrotonic length of the equivalent cylinder representing the cell processes was estimated to be 0.49 from the whole-cell data and 0.79 from the sharp electrode recordings. This implies that at rest there is only a 10% decrement in steady-state membrane voltage along the length of the dendrite due to shunting across the membrane resistance; small synaptic events occurring in the distal dendritic tree will therefore have a more substantial influence on the soma than previous analyses suggested.(ABSTRACT TRUNCATED AT 400 WORDS)

Remodelling during development of the Purkinje cell dendritic tree in the mouse

1984 ◽  
Vol 221 (1224) ◽  
pp. 349-367 ◽  
Keyword(s):  
Purkinje Cell ◽  
Granule Cells ◽  
Dendritic Tree ◽  
Growth Front ◽  
Cell Number ◽  
Terminal Segment ◽  
Entire Study ◽  
Dendritic Trees ◽  
Cell Counts ◽  
Parallel Fibres

The development of the Purkinje cells in normal C57 mice was studied from 7-100 d post natum . The growth of the dendritic trees was analysed both metrically and topologically using the method of vertex analysis (Berry & Flinn 1983a). Granule and Purkinje cell counts were made so that Purkinje cell segment production could be correlated with the number of parallel fibres deposited. Both topological and metrical results indicate that from 7 to 30 d post natum the Purkinje cell dendritic trees expand massively; accounting for 87 % of total segment elaboration, reaching their lateral boundaries by 12-15 d post natum and then advancing towards the pial surface. Continued lateral expansion is constrained by the proximity of dendrites from neighbouring trees. Growth proceeds upwards through the neuropil as a front of prolific random terminal branching with inhibitory forces acting at the edges of the growth corridor and behind the growth front to prevent overlapping of dendrites. By 30 d post natum all boundaries are reached and the size of the dendritic field is fixed. Trees averaged 711.2 segments ±21.45 with a mean distance from root to terminal segment of 133.5 ± 2.9 pm. The Va/Vb vertex ratios and the levels of trichotomy during this period indicate that branching patterns deviate from pure random terminal additions in a dichotomous tree. There is opportunity for non-random growth at the areas of inhibitory action. Beyond 30 d post natum remodelling occurs within the arbor which involves segment loss in the subpial region (orders above 16) and segment elaboration within the tree (orders 8- 16) causing increased density of dendrites and overlapping of segments. The frequencies of segments and terminals are restored to symmetrical distributions through the orders of the trees from the skewed distributions associated with the frontal advance in earlier growth. During remodelling the Va/Vb vertex ratios and percentage of trichotomous nodes are consistent with growth through dichotomous random terminal branching. Path lengths of 8 um between each order are seen as regular increments throughout entire trees at 100 d post natum. The final tree produced is indistinguishable from a network grown entirely by random terminal dichotomous branching with some 6% trichotomy and a Va/Vb vertex ratios of 0.92. Granule cell number within the granular layer increases rapidly up to 15 d post natum after which cell death causes a decrease to stable levels beyond 30 d post natum . Purkinje cell number is constant throughout the entire study. However, there is no correlation between the numbers of granule cells (parallel fibres) per Purkinje cell and the number of Purkinje cell branches elaborated beyond early development.

Electrotonic parameters of rat dentate granule cells measured using short current pulses and HRP staining

1983 ◽  
Vol 50 (5) ◽  
pp. 1080-1097 ◽  
Author(s):  
D. Durand ◽  
P. L. Carlen ◽  
N. Gurevich ◽  
A. Ho ◽  
H. Kunov
Keyword(s):  
Time Constant ◽  
Granule Cells ◽  
Short Pulse ◽  
Dendritic Tree ◽  
Input Resistance ◽  
Synaptic Activity ◽  
Branch Points ◽  
Pulse Technique ◽  
Current Pulses ◽  
Branching Points

The passive electrotonic parameters of nerve cells in the dentate gyrus of the rat were studied in vitro. Intracellular recordings from 30 granule cells and 3 pyramidal basket cells followed by intracellular injection of horseradish peroxidase (HRP), allowed calculations of input resistance (RN), membrane time constant (tau m), electrotonic length (L), ratio of dendritic to somatic conductance (rho), membrane specific capacitance and resistance (Rm, Cm), and specific axoplasmic resistance (Ri). The analysis of the voltage decays from long saturating (100 ms) and short (0.5 ms) current pulses showed that the short-pulse method gave better resolution for the measurement of the time constants and avoided some of the time-dependent nonlinearities but required larger currents than the long pulse. Morphological analysis of 49 branching points taken from the dendritic trees of granule cells showed that the branching power, n, is equal to 1.56 +/- 0.186 and was fairly constant throughout the tree. Given the fact that all dendrites have approximately the same length and number of branch points, the granule cell dendritic tree can be meaningfully collapsed into an equivalent cable. Moreover, electrophysiological data suggested that the cable had a "sealed" end or at least a high-impedance termination. Based on an equivalent cable model with a sealed end and a lumped soma impedance, a method was implemented to analyze the multiexponential decays from hyperpolarizing current pulses and to solve the equations of the model. This was done successfully in only 40% of the cells and yielded the following mean values for L = 1.13 and rho = 7.58. From the measurements of the soma surface area (S) and the equivalent cable diameter (D), the average specific membrane parameters were calculated: Rm = 2,726 alpha x cm2, Cm = 5.24 microF/cm2, Ri = 101 alpha x cm. The input resistance and time constant of the granule cells as measured from the short-pulse technique averaged to RN 58.57 M alpha and tau m = 16.21 ms. The failure of the model to fit 60% of the cells was interpreted to be due to the presence of a somatic shunt resulting from electrode injury, tonic synaptic activity, a lower somatic membrane specific resistance, or electronic coupling.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals The flavonoid 7,8-DHF fosters prenatal brain proliferation potency in a mouse model of Down syndrome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fiorenza Stagni ◽  
Beatrice Uguagliati ◽  
Marco Emili ◽  
Andrea Giacomini ◽  
Renata Bartesaghi ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Intellectual Disability ◽  
Granule Cells ◽  
Neonatal Period ◽  
Hippocampal Neurogenesis ◽  
Chromosome 21 ◽  
Prenatal Treatment ◽  
Long Term Effects ◽  
Neonatal Treatment

AbstractNeurogenesis impairment is a key determinant of intellectual disability in Down syndrome (DS), a genetic pathology due to triplication of chromosome 21. Since neurogenesis ceases after birth, apart in the hippocampus and olfactory bulb, the only means to tackle the problem of neurogenesis impairment in DS at its root is to intervene during gestation. A few studies in DS mouse models show that this is possible, although the drugs used may raise caveats in terms of safety. We previously found that neonatal treatment with 7,8-dihydroxyflavone (7,8-DHF), a flavonoid present in plants, restores hippocampal neurogenesis in the Ts65Dn model of DS. The goal of the current study was to establish whether prenatal treatment with 7,8-DHF improves/restores overall brain proliferation potency. Pregnant Ts65Dn females received 7,8-DHF from embryonic day 10 until delivery. On postnatal day 2 (P2) the pups were injected with BrdU and were killed after either 2 h or 52–60 days (P52–60). Evaluation of the number of proliferating (BrdU+) cells in various forebrain neurogenic niches of P2 mice showed that in treated Ts65Dn mice proliferation potency was improved or even restored in most of the examined regions, including the hippocampus. Quantification of the surviving BrdU+ cells in the dentate gyrus of P52–60 mice showed no difference between treated and untreated Ts65Dn mice. At P52–60, however, treated Ts65Dn mice exhibited a larger number of granule cells in comparison with their untreated counterparts, although their number did not reach that of euploid mice. Results show that 7,8-DHF has a widespread impact on prenatal proliferation potency in Ts65Dn mice and exerts mild long-term effects. It remains to be established whether treatment extending into the neonatal period can lead to an improvement in brain development that is retained in adulthood.

Ca(2+)-dependent plasticity of miniature inhibitory postsynaptic currents after amputation of dendrites in central neurons

1995 ◽  
Vol 73 (5) ◽  
pp. 1763-1773 ◽  
Author(s):  
I. Soltesz ◽  
I. Mody
Keyword(s):  
Granule Cells ◽  
Dendritic Tree ◽  
Granule Cell Layer ◽  
Na Channel ◽  
Decay Kinetics ◽  
Whole Cell ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Population Spikes ◽  
Whole Cell Recordings

1. The effects of cutting off the bulk (> 2/3) of the dendritic tree (dendrotomy) on GABAergic miniature inhibitory postsynaptic currents (mIPCSs) were studied in granule cells of the adult rat dentate gyrus in 400-microns-thick slices in vitro. 2. After dendrotomy carried out in warm (32 degrees C) control artificial cerebrospinal fluid (ACSF), only small antidromic population spikes could be evoked in the granule cell layer, and no viable whole cell recordings could be obtained. However, when dendrotomy was performed in cold (8-10 degrees C) control ACSF, the amplitude of the antidromic population spikes increased, and stable whole cell recordings became possible. 3. Whole cell recordings, with CsCl-filled pipettes, from granule cells dendrotomized in cold control ACSF, revealed significant alterations, lasting > 10 h, in the decay kinetics of mIPSACs. The change consisted of a calcium-dependent transformation of the normal, single exponential decay into a prolonged double exponential that effectively increased the charge transferred by the synaptic events (the total area of the currents) by 67%. When 30 mM 1,2 bis-(2-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA) was included in the pipette, the changes in the mIPSCs decay kinetics could still be observed after dendrotomy, indicating that the maintenance phase of this plasticity did not depend on elevated intracellular calcium levels. 4. Viable whole cell recordings could also be obtained in dendrotomized granule cells when the amputation of dendrites was carried out at 32 degrees C after incubation for 2 h with the cell-permeant Ca2+ chelator, BAPTA-AM (50 microM), or the cutting process was done in an ACSF containing either a combination of excitatory amino acid receptor antagonists 2-amino-5-phosphonovaleric acid (APV; 25 microM) + 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM), a blocker of intracellular Ca2+ release dantrolene-Na (20 microM), or the voltage-gated Na+ channel blocker tetrodotoxin (TTX; 1 microM). 5. After dendrotomy in BAPTA-AM, APV + CNQX, APV + CNQX + TTX, and/or dantrolene, the changes in decay kinetics were prevented, indicating that a rise in intracellular Ca2+ concentration plays a pivotal role in this plasticity. 6. Computer simulations of mIPSCs suggested that changes in single channel kinetics alone can, in principle, account for the Ca(2+)-dependent changes in mIPSC decay kinetics. 7. These findings are consistent with a lasting Ca(2+)-dependent increase in gamma-aminobutyric acid-A (GABAA) receptor function in cells that survive physical injury to their dendrites.

GABAergic hyperinnervation of dentate granule cells in the Ts65Dn mouse model of down syndrome: Exploring the role ofApp

Hippocampus ◽  
2016 ◽  
Vol 26 (12) ◽  
pp. 1641-1654 ◽  
Author(s):  
Fatemeh S. Mojabi ◽  
Atoossa Fahimi ◽  
Shahrzad Moghadam ◽  
Sarah Moghadam ◽  
M. Windy McNerneny ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Mouse Model ◽  
Granule Cells ◽  
Ts65dn Mouse ◽  
Dentate Granule Cells

scholarly journals Dentate Granule Cells Recruited in the Home Environment Display Distinctive Properties

2021 ◽  
Vol 14 ◽  
Author(s):  
Claire Pléau ◽  
Angélique Peret ◽  
Edouard Pearlstein ◽  
Thomas Scalfati ◽  
Alexandre Vigier ◽  
...  
Keyword(s):  
Home Environment ◽  
Home Cage ◽  
Granule Cells ◽  
Ex Vivo ◽  
Dendritic Tree ◽  
Input Resistance ◽  
Dentate Granule Cells ◽  
Shunting Inhibition ◽  
Cage Condition ◽  
Functional Features

The dentate granule cells (DGCs) play a crucial role in learning and memory. Many studies have described the role and physiological properties of these sparsely active neurons using different behavioral contexts. However, the morpho-functional features of DGCs recruited in mice maintained in their home cage (without training), considered as a baseline condition, have not yet been established. Using fosGFP transgenic mice, we observed ex vivo that DGCs recruited in animals maintained in the home cage condition are mature neurons that display a longer dendritic tree and lower excitability compared with non-activated cells. The higher GABAA receptor-mediated shunting inhibition contributes to the lower excitability of DGCs activated in the home environment by shifting the input resistance towards lower values. Remarkably, that shunting inhibition is neither observed in non-activated DGCs nor in DGCs activated during training in virtual reality. In short, our results suggest that strong shunting inhibition and reduced excitability could constitute a distinctive neural signature of mature DGCs recruited in the context of the home environment.

Passive Normalization of Synaptic Integration Influenced by Dendritic Architecture

1999 ◽  
Vol 82 (6) ◽  
pp. 3268-3285 ◽  
Author(s):  
David B. Jaffe ◽  
Nicholas T. Carnevale
Keyword(s):  
Pyramidal Neurons ◽  
Granule Cells ◽  
Primary Dendrite ◽  
Current Source ◽  
Dendritic Tree ◽  
Pyramidal Cells ◽  
Neuronal Morphology ◽  
Synaptic Integration ◽  
Dendritic Location ◽  
A Current

We examined how biophysical properties and neuronal morphology affect the propagation of individual postsynaptic potentials (PSPs) from synaptic inputs to the soma. This analysis is based on evidence that individual synaptic activations do not reduce local driving force significantly in most central neurons, so each synapse acts approximately as a current source. Therefore the spread of PSPs throughout a dendritic tree can be described in terms of transfer impedance ( Zc ), which reflects how a current applied at one location affects membrane potential at other locations. We addressed this topic through four lines of study and uncovered new implications of neuronal morphology for synaptic integration. First, Zc was considered in terms of two-port theory and contrasted with dendrosomatic voltage transfer. Second, equivalent cylinder models were used to compare the spatial profiles of Zc and dendrosomatic voltage transfer. These simulations showed that Zc is less affected by dendritic location than voltage transfer is. Third, compartmental models based on morphological reconstructions of five different neuron types were used to calculate Zc , input impedance ( ZN ), and voltage transfer throughout the dendritic tree. For all neurons, there was no significant variation of Zc with location within higher-order dendrites. Furthermore, Zc was relatively independent of synaptic location throughout the entire cell in three of the five neuron types (CA3 interneurons, CA3 pyramidal neurons, and dentate granule cells). This was quite unlike ZN , which increased with distance from the soma and was responsible for a parallel decrease of voltage transfer. Fourth, simulations of fast excitatory PSPs (EPSPs) were consistent with the analysis of Zc ; peak EPSP amplitude varied <20% in the same three neuron types, a phenomenon that we call “passive synaptic normalization” to underscore the fact that it does not require active currents. We conclude that the presence of a long primary dendrite, as in CA1 or neocortical pyramidal cells, favors substantial location-dependent variability of somatic PSP amplitude. In neurons that lack long primary dendrites, however, PSP amplitude at the soma will be much less dependent on synaptic location.

scholarly journals MCT8 deficiency in Purkinje cells disrupts embryonic chicken cerebellar development

2017 ◽  
Vol 232 (2) ◽  
pp. 259-272 ◽  
Author(s):  
Joke Delbaere ◽  
Pieter Vancamp ◽  
Stijn L J Van Herck ◽  
Nele M A Bourgeois ◽  
Mary J Green ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Purkinje Cell ◽  
Purkinje Cells ◽  
Granule Cells ◽  
Dendritic Tree ◽  
Monocarboxylate Transporter ◽  
Cerebellar Development ◽  
Germinal Layer ◽  
Radial Migration ◽  
Mct8 Deficiency

Inactivating mutations in the human SLC16A2 gene encoding the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) result in the Allan–Herndon–Dudley syndrome accompanied by severe locomotor deficits. The underlying mechanisms of the associated cerebellar maldevelopment were studied using the chicken as a model. Electroporation of an MCT8-RNAi vector into the cerebellar anlage of a 3-day-old embryo allowed knockdown of MCT8 in Purkinje cell precursors. This resulted in the downregulation of the thyroid hormone-responsive gene RORα and the Purkinje cell-specific differentiation marker LHX1/5 at day 6. MCT8 knockdown also results in a smaller and less complex dendritic tree at day 18 suggesting a pivotal role of MCT8 for cell-autonomous Purkinje cell maturation. Early administration of the thyroid hormone analogue 3,5,3′-triiodothyroacetic acid partially rescued early Purkinje cell differentiation. MCT8-deficient Purkinje cells also induced non-autonomous effects as they led to a reduced granule cell precursor proliferation, a thinner external germinal layer and a loss of PAX6 expression. By contrast, at day 18, the external germinal layer thickness was increased, with an increase in presence of Axonin-1-positive post-mitotic granule cells in the initial stage of radial migration. The concomitant accumulation of presumptive migrating granule cells in the molecular layer, suggests that inward radial migration to the internal granular layer is stalled. In conclusion, early MCT8 deficiency in Purkinje cells results in both cell-autonomous and non-autonomous effects on cerebellar development and indicates that MCT8 expression is essential from very early stages of development, providing a novel insight into the ontogenesis of the Allan–Herndon–Dudley syndrome.

Quantifying the Role of Inhibition in Associative Long-Term Potentiation in Dentate Granule Cells With Computational Models

1997 ◽  
Vol 78 (1) ◽  
pp. 103-116 ◽  
Author(s):  
William R. Holmes ◽  
William B. Levy
Keyword(s):  
Computational Models ◽  
Granule Cells ◽  
Dendritic Tree ◽  
Long Term Potentiation ◽  
Inhibitory Synapses ◽  
Shunting Inhibition ◽  
Term Potentiation ◽  
Spatial Convergence ◽  
Voltage Attenuation

Holmes, William R. and William B. Levy. Quantifying the role of inhibition in associative long-term potentiation in dentate granule cells with computational models. J. Neurophysiol. 78: 103–116, 1997. In the dentate gyrus, coactivation of a mildly strong ipsilateral perforant path (pp) input with a weak contralateral pp input will not induce associative long-term potentiation in the weak input path unless both inputs project to the same part of the molecular layer. This “spatial convergence requirement” is thought to arise from either voltage attenuation between input locations or inhibition. Simulations with a detailed model of a dentate granule cell were performed to rule out voltage attenuation and to quantify the inhibition necessary to obtain the spatial convergence requirement. Strong lateral and weak medial or strong medial and weak lateral pp input were activated eight times at 400 Hz. Calcium current through N-methyl-d-aspartate receptor channels and subsequent changes in calcium concentration and the concentration of calmodulin bound with four calcium ions ([Cal-Ca4]) in the spine head were computed for a medial and a lateral pp synapse. To satisfy the spatial convergence requirement, peak [Cal-Ca4] had to be much larger in the strongly activated path synapse than in the weakly activated path synapse. With no inhibition in the model, differences in peak [Cal-Ca4] at the two synapses were small, ruling out voltage attenuation as the explanation of the spatial convergence requirement. However, with shunting inhibition, modeled by reducing membrane resistivity to 1,600 Ω cm2 in the distal two-thirds of the dendritic tree, peak [Cal-Ca4] was 3–5 times larger in the strongly activated path synapse than in the weakly activated path synapse. The magnitude of shunting inhibition was varied to determine the level that maximized this difference in peak [Cal-Ca4]. For strong lateral and weak medial pp input, the optimal level was one that prevented the cell from firing an action potential. For strong medial and weak lateral pp input, the optimal level was one at which the cell fired two action potentials. The distribution of shunting inhibition that best satisfied the spatial convergence requirement was inhibition on the distal two-thirds of the dendritic tree with or without inhibition at the soma, with inhibition stronger in the distal third than in the middle third. It was estimated that the number of inhibitory synapses involved in the shunting inhibition should be 25–50% of the number of excitatory synapses activated by the eight-pulse, 400-Hz tetanus. This number could be 20–50% of the total number of inhibitory synapses in the distal two-thirds of the dendritic tree. The addition of a single inhibitory synapse on a dendrite had a significant effect on peak spine head [Cal-Ca4] in nearby spines. Inhibitory synapses had to be activated four or more times at 100 Hz for effective shunting to take place, and the inhibition had to begin no later than2–5 ms after the first excitatory input. The results suggest that inhibition can isolate potentiated synapses to particular dendritic domains and that the location of activated inhibitory synapses may affect potentiation of individual synapses on individual dendrites.

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