scholarly journals DENTATE GRANULE CELLS ARE HYPEREXCITABLE IN THE TGF344-AD RAT MODEL OF ALZHEIMER'S DISEASE

2021 ◽  
Author(s):  
Lindsey Smith ◽  
Anthoni M Goodman ◽  
Lori L McMahon
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Frequency ◽  
Granule Cells ◽  
Perforant Path ◽  
Membrane Properties ◽  
High Frequency Stimulation ◽  
Dentate Granule Cells ◽  
Active Membrane ◽  
Mechanistic Investigation

The dentate gyrus is both a critical gatekeeper for hippocampal signal processing and one of the first regions to dysfunction in Alzheimer's disease (AD). Accordingly, the appropriate balance of excitation and inhibition through the dentate is a compelling target for mechanistic investigation and therapeutic intervention of early AD. Previously, we reported increased LTP magnitude at medial perforant path-dentate granule cell (MPP-DGC) synapses in slices from TgF344-AD rats compared to Wt as early as 6 months. We next determined that the enhanced LTP magnitude was due to heightened function of β-ARs leading us to ask if dentate granule cells (DGCs) also have modified passive or active membrane properties which may also contribute to hyperexcitability or aberrant hippocampal processing. Although there was no detectable difference in spine density and presynaptic release probability, dentate granule cells (DGCs) themselves might have increased electrical response to synaptic input during LTP induction, which was measured as a significant increase in charge transfer during high-frequency stimulation. In this study, we found passive membrane properties and active membrane properties are altered, leading to increased TgF344-AD DGC excitability. Specifically, TgF344-AD DGCs have an increased input resistance and decreased rheobase, decreased sag, and increased action potential (AP) spike accommodation. Importantly, we find that the voltage response increased in DGCs from TgF344-AD compared to Wt accompanied by decreased delay to fire the first AP, indicating that for the same amount of depolarizing current injection TgF344-AD DGCs membranes are more excitable. Taken together, DGCs of TgF344-AD rats are more excitable, but due to heightened accommodation, may be unable to discharge at high frequency for longer durations of time, compared to their Wt littermates.

Neurofibrillary tangles in the dentate granule cells of patients with Alzheimer's disease, Lewy body disease and progressive supranuclear palsy

1997 ◽  
Vol 93 (1) ◽  
pp. 7-12 ◽  
Author(s):  
K. Wakabayashi ◽  
Lawrence A. Hansen ◽  
Inez Vincent ◽  
Margaret Mallory ◽  
E. Masliah
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Progressive Supranuclear Palsy ◽  
Neurofibrillary Tangles ◽  
Lewy Body ◽  
Granule Cells ◽  
Lewy Body Disease ◽  
Dentate Granule Cells

Decrement of GABAA receptor-mediated inhibitory postsynaptic currents in dentate granule cells in epileptic hippocampus

1996 ◽  
Vol 75 (5) ◽  
pp. 1901-1908 ◽  
Author(s):  
M. Isokawa
Keyword(s):  
Nmda Receptor ◽  
Granule Cells ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Patch Clamp Recording ◽  
Dentate Granule Cells ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Pilocarpine Model ◽  
Frequency Stimulation

1. Inhibitory postsynaptic currents (IPSCs) were studied in hippocampal dentate granule cells (DGCs) in the pilocarpine model and human temporal lobe epilepsy, with the use of the whole cell patch-clamp recording technique in slice preparations. 2. In the pilocarpine model, hippocampal slices were prepared from rats that were allowed to experience spontaneous seizures for 2 mo. Human hippocampal specimens were obtained from epileptic patients who underwent surgical treatment for medically intractable seizures. 3. IPSCs were generated by single perforant path stimulation and recorded at a membrane potential (Vm) of 0 mV near the reversal potential of glutamate excitatory postsynaptic currents in the voltage-clamp recording. IPSCs were pharmacologically identified as gamma-aminobutyric acid-A (GABAA) IPSCs by 10 microM bicuculline methiodide. 4. During low-frequency stimulation, IPSCs were not different in amplitude among non-seizure-experienced rat hippocampi, human nonsclerotic hippocampi, seizure-experienced rat hippocampi, and human sclerotic hippocampi. In the last two groups of DGCs, current-clamp recordings indicated the presence of prolonged excitatory postsynaptic potentials (EPSPs) mediated by the N-methyl-D-aspartate (NMDA) receptor. 5. High-frequency stimulation, administered at Vm = -30 mV to activate NMDA currents, reduced GABAA IPSC amplitude specifically in seizure-experienced rat hippocampi (t = 2.5, P < 0.03) and human sclerotic hippocampi (t = 7.7, P < 0.01). This reduction was blocked by an NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (APV) (50 microM). The time for GABAA IPSCs to recover to their original amplitude was also shortened by the application of APV. 6. I conclude that, when intensively activated, NMDA receptor-mediated excitatory transmission may interact with GABAergic synaptic inhibition in DGCs in seizure-experienced hippocampus to transiently reduce GABA(A) receptor-channel function. Such interactions may contribute to give rise to epileptic excitation in chronically seizure-prone hippocampus.

scholarly journals Effect of Adrenalectomy on Membrane Properties and Synaptic Potentials in Rat Dentate Granule Cells

2001 ◽  
Vol 85 (2) ◽  
pp. 699-707 ◽  
Author(s):  
M. Joëls ◽  
C. Stienstra ◽  
Y. Karten
Keyword(s):  
Dentate Gyrus ◽  
Granule Cells ◽  
Cell Loss ◽  
Perforant Path ◽  
Membrane Properties ◽  
Similar Extent ◽  
Dentate Granule Cells ◽  
Field Response ◽  
Induced Changes ◽  
Synaptic Responses

Adrenalectomy is known to accelerate both neurogenesis and cell death of granule cells located in the suprapyramidal blade of the rat dentate gyrus. Three days after adrenalectomy, some granule cells have already died by apoptosis while newly formed cells are not yet incorporated in the cell layer, resulting in a temporary loss of granule cells. Concomitantly, the field response to stimulation of perforant path afferents is reduced. While the temporary cell loss is likely to attenuate synaptic field responses, adrenalectomy-induced changes in properties of the surviving cells may also contribute to the reduction in field response amplitude. To address this possibility, we here investigated the membrane properties and synaptic responses of dentate granule cells, 3 days after adrenalectomy. We found that passive and most of the active membrane properties of granule cells in adrenalectomized rats were not significantly different from the cell properties in sham-operated controls. However, intracellularly recorded synaptic responses from surviving granule cells were markedly reduced after adrenalectomy. The N-methyl-d-aspartate (NMDA)– and the non-NMDA receptor–mediated components were reduced to a similar extent, suggesting that the attenuation of synaptic transmission after adrenalectomy could be partly of presynaptic origin. The data indicate that the earlier observed attenuation of synaptic field responses after adrenalectomy may be partly due to a diminished glutamatergic input to the dentate gyrus and not exclusively to a loss of granule cells participating in the synaptic circuit.

A high frequency of apolipoprotein E4 isoprotein in Japanese patients with late-onset nonfamilial Alzheimer's disease

1993 ◽  
Vol 163 (2) ◽  
pp. 166-168 ◽  
Author(s):  
Akira Ueki ◽  
Mikihiko Kawano ◽  
Yoshio Namba ◽  
Masanobu Kawakami ◽  
Kazuhiko Ikeda
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Frequency ◽  
Late Onset ◽  
Japanese Patients ◽  
Apolipoprotein E4

scholarly journals Effects of High-Frequency Cranial Electrostimulation on the Rest-Activity Rhythm and Salivary Cortisol in Alzheimer’s Disease

2006 ◽  
Vol 22 (4) ◽  
pp. 267-272 ◽  
Author(s):  
Erik Scherder ◽  
Dirk Knol ◽  
Marie-Jose van Tol ◽  
Eus van Someren ◽  
Jan-Berend Deijen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Salivary Cortisol ◽  
High Frequency ◽  
Activity Rhythm ◽  
Rest Activity

High frequency of getting out of bed in patients with Alzheimer's disease monitored by non-wearable actigraphy

2018 ◽  
Vol 19 (2) ◽  
pp. 130-134 ◽  
Author(s):  
Yoko Higami ◽  
Miyae Yamakawa ◽  
Kazue Shigenobu ◽  
Kei Kamide ◽  
Kiyoko Makimoto
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Frequency

scholarly journals High frequency of open-angle glaucoma in Japanese patients with Alzheimer's disease

2006 ◽  
Vol 246 (1-2) ◽  
pp. 79-83 ◽  
Author(s):  
Hiroki Tamura ◽  
Hideshi Kawakami ◽  
Takashi Kanamoto ◽  
Tomoko Kato ◽  
Tomoko Yokoyama ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Frequency ◽  
Open Angle Glaucoma ◽  
Japanese Patients ◽  
Open Angle
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