Aging Alters Olfactory Bulb Network Oscillations and Connectivity: Relevance for Aging-Related Neurodegeneration Studies

The aging process eventually cause a breakdown in critical synaptic plasticity and connectivity leading to deficits in memory function. The olfactory bulb (OB) and the hippocampus, both regions of the brain considered critical for the processing of odors and spatial memory, are commonly affected by...

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Main Authors: A. Ahnaou, D. Rodriguez-Manrique, S. Embrechts, R. Biermans, N. V. Manyakov, S. A. Youssef, W. H. I. M. Drinkenburg
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2020/1703969
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author A. Ahnaou
D. Rodriguez-Manrique
S. Embrechts
R. Biermans
N. V. Manyakov
S. A. Youssef
W. H. I. M. Drinkenburg
author_facet A. Ahnaou
D. Rodriguez-Manrique
S. Embrechts
R. Biermans
N. V. Manyakov
S. A. Youssef
W. H. I. M. Drinkenburg
author_sort A. Ahnaou
collection DOAJ
description The aging process eventually cause a breakdown in critical synaptic plasticity and connectivity leading to deficits in memory function. The olfactory bulb (OB) and the hippocampus, both regions of the brain considered critical for the processing of odors and spatial memory, are commonly affected by aging. Using an aged wild-type C57B/6 mouse model, we sought to define the effects of aging on hippocampal plasticity and the integrity of cortical circuits. Specifically, we measured the long-term potentiation of high-frequency stimulation (HFS-LTP) at the Shaffer-Collateral CA1 pyramidal synapses. Next, local field potential (LFP) spectra, phase-amplitude theta-gamma coupling (PAC), and connectivity through coherence were assessed in the olfactory bulb, frontal and entorhinal cortices, CA1, and amygdala circuits. The OB of aged mice showed a significant increase in the number of histone H2AX-positive neurons, a marker of DNA damage. While the input-output relationship measure of basal synaptic activity was found not to differ between young and aged mice, a pronounced decline in the slope of field excitatory postsynaptic potential (fEPSP) and the population spike amplitude (PSA) were found in aged mice. Furthermore, aging was accompanied by deficits in gamma network oscillations, a shift to slow oscillations, reduced coherence and theta-gamma PAC in the OB circuit. Thus, while the basal synaptic activity was unaltered in older mice, impairment in hippocampal synaptic transmission was observed only in response to HFS. However, age-dependent alterations in neural network appeared spontaneously in the OB circuit, suggesting the neurophysiological basis of synaptic deficits underlying olfactory processing. Taken together, the results highlight the sensitivity and therefore potential use of LFP quantitative network oscillations and connectivity at the OB level as objective electrophysiological markers that will help reveal specific dysfunctional circuits in aging-related neurodegeneration studies.
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spelling doaj-art-f5774b2d144549bfb075454a1d8308a72025-02-03T01:04:06ZengWileyNeural Plasticity2090-59041687-54432020-01-01202010.1155/2020/17039691703969Aging Alters Olfactory Bulb Network Oscillations and Connectivity: Relevance for Aging-Related Neurodegeneration StudiesA. Ahnaou0D. Rodriguez-Manrique1S. Embrechts2R. Biermans3N. V. Manyakov4S. A. Youssef5W. H. I. M. Drinkenburg6Department of Neuroscience, Janssen Research & Development, a Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, BelgiumDepartment of Neuroscience, Janssen Research & Development, a Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, BelgiumDepartment of Neuroscience, Janssen Research & Development, a Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, BelgiumDepartment of Neuroscience, Janssen Research & Development, a Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, BelgiumDepartment of Neuroscience, Janssen Research & Development, a Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, BelgiumDepartment of Non-Clinical Safety, Janssen Research & Development, a Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, BelgiumDepartment of Neuroscience, Janssen Research & Development, a Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, BelgiumThe aging process eventually cause a breakdown in critical synaptic plasticity and connectivity leading to deficits in memory function. The olfactory bulb (OB) and the hippocampus, both regions of the brain considered critical for the processing of odors and spatial memory, are commonly affected by aging. Using an aged wild-type C57B/6 mouse model, we sought to define the effects of aging on hippocampal plasticity and the integrity of cortical circuits. Specifically, we measured the long-term potentiation of high-frequency stimulation (HFS-LTP) at the Shaffer-Collateral CA1 pyramidal synapses. Next, local field potential (LFP) spectra, phase-amplitude theta-gamma coupling (PAC), and connectivity through coherence were assessed in the olfactory bulb, frontal and entorhinal cortices, CA1, and amygdala circuits. The OB of aged mice showed a significant increase in the number of histone H2AX-positive neurons, a marker of DNA damage. While the input-output relationship measure of basal synaptic activity was found not to differ between young and aged mice, a pronounced decline in the slope of field excitatory postsynaptic potential (fEPSP) and the population spike amplitude (PSA) were found in aged mice. Furthermore, aging was accompanied by deficits in gamma network oscillations, a shift to slow oscillations, reduced coherence and theta-gamma PAC in the OB circuit. Thus, while the basal synaptic activity was unaltered in older mice, impairment in hippocampal synaptic transmission was observed only in response to HFS. However, age-dependent alterations in neural network appeared spontaneously in the OB circuit, suggesting the neurophysiological basis of synaptic deficits underlying olfactory processing. Taken together, the results highlight the sensitivity and therefore potential use of LFP quantitative network oscillations and connectivity at the OB level as objective electrophysiological markers that will help reveal specific dysfunctional circuits in aging-related neurodegeneration studies.http://dx.doi.org/10.1155/2020/1703969
spellingShingle A. Ahnaou
D. Rodriguez-Manrique
S. Embrechts
R. Biermans
N. V. Manyakov
S. A. Youssef
W. H. I. M. Drinkenburg
Aging Alters Olfactory Bulb Network Oscillations and Connectivity: Relevance for Aging-Related Neurodegeneration Studies
Neural Plasticity
title Aging Alters Olfactory Bulb Network Oscillations and Connectivity: Relevance for Aging-Related Neurodegeneration Studies
title_full Aging Alters Olfactory Bulb Network Oscillations and Connectivity: Relevance for Aging-Related Neurodegeneration Studies
title_fullStr Aging Alters Olfactory Bulb Network Oscillations and Connectivity: Relevance for Aging-Related Neurodegeneration Studies
title_full_unstemmed Aging Alters Olfactory Bulb Network Oscillations and Connectivity: Relevance for Aging-Related Neurodegeneration Studies
title_short Aging Alters Olfactory Bulb Network Oscillations and Connectivity: Relevance for Aging-Related Neurodegeneration Studies
title_sort aging alters olfactory bulb network oscillations and connectivity relevance for aging related neurodegeneration studies
url http://dx.doi.org/10.1155/2020/1703969
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