Decreased Rhythmic GABAergic Septal Activity and Memory-Associated θ Oscillations after Hippocampal Amyloid-β Pathology in the Rat

Villette, Vincent; Poindessous‐Jazat, Frédérique; Simon, A.; Léna, Clément; Roullot, Elodie; Bellessort, Brice; Epelbaum, Jacques; Dutar, P.; Stéphan, Aline

doi:10.1523/jneurosci.6284-09.2010

Cited by 97 publications

(94 citation statements)

References 91 publications

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“…Although in this work, we only focus on the system dynamical changes caused by the pathological changes in the hippocampal pyramidal neurons, it should be admitted that the Aβ-indued hippocampal dysfunction may be more complex. For example, it has been shown in (Villette et al 2010;Colom et al 2010) that Aβ-induced GABAergic and cholinergic system degeneration in the medial septum may also cause hippocampal dysfunctions. GABAergic neurons inhibit hippocampal OLM and basket neurons and act as a hippocampal theta rhythm pacemaker and cholinergic neurons control the acetylcholine level in the hippocampus, which can change the dynamics of pyramidal neurons and synapses.…”

Section: Discussionmentioning

confidence: 99%

Beta-amyloid induced changes in A-type K+ current can alter hippocampo-septal network dynamics

et al. 2011

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Alzheimer's disease (AD) progression is usually associated with memory deficits and cognitive decline. A hallmark of AD is the accumulation of beta-amyloid (Aβ) peptide, which is known to affect the hippocampal pyramidal neurons in the early stage of AD. Previous studies have shown that Aβ can block A-type K(+) currents in the hippocampal pyramidal neurons and enhance the neuronal excitability. However, the mechanisms underlying such changes and the effects of the hyper-excited pyramidal neurons on the hippocampo-septal network dynamics are still to be investigated. In this paper, Aβ-blocked A-type current is simulated, and the resulting neuronal and network dynamical changes are evaluated in terms of the theta band power. The simulation results demonstrate an initial slight but significant theta band power increase as the A-type current starts to decrease. However, the theta band power eventually decreases as the A-type current is further decreased. Our analysis demonstrates that Aβ blocked A-type currents can increase the pyramidal neuronal excitability by preventing the emergence of a steady state. The increased theta band power is due to more pyramidal neurons recruited into spiking mode during the peak of pyramidal theta oscillations. However, the decreased theta band power is caused by the spiking phase relationship between different neuronal populations, which is critical for theta oscillation, is violated by the hyper-excited pyramidal neurons. Our findings could provide potential implications on some AD symptoms, such as memory deficits and AD caused epilepsy.

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Section: Discussionmentioning

confidence: 99%

Beta-amyloid induced changes in A-type K+ current can alter hippocampo-septal network dynamics

et al. 2011

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“…In fact, impairment of hippocampal theta oscillation was considered to underlie compromised hippocampal-dependent cognitive function in APP/PS1 mice (Howlett et al, 2004;Villette et al, 2010). Therefore, we studied the efficacy…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Hippocampal network dynamics in response to α7 nACh receptors activation in amyloid-β overproducing transgenic mice

Stoiljković

Kelley

Hajós

et al. 2016

Neurobiology of Aging

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“…A decreased neocortical inhibition in an AD model has been reported by Busche et al (2008), who found that near amyloid plaques neurons are hyperactive, probably because of a less efficient inhibition by GABAergic neurons. Moreover, it has been recently shown that rhythmic bursting neurons of the medial septum, which are necessary for hippocampal theta rhythm and learning and are fast spiking neurons expressing Kv3.1 (Henderson et al 2010), fire at lower rates after injection of betaamyloid (Villette et al 2010). Therefore, it can be hypothesised that the reduction of Kv3.1 expression could modify Kv3 current density and channel stoichiometry and thereby play a role in the impairment of inhibition in neocortical networks in AD.…”

Section: Kv3 Expression In Appps1 Micementioning

confidence: 99%

Brain Expression of Kv3 Subunits During Development, Adulthood and Aging and in a Murine Model of Alzheimer’s Disease

et al. 2011

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In neurons, voltage-dependent Kv3 potassium channels are essential for the generation of action potentials at high frequency. A dysregulation of the Kv3.1 and Kv3.4 channel subunits has been suggested to contribute to neuronal and glial alterations in Alzheimer's disease, but a quantitative evaluation of these subunits in a mouse model of the pathology is still lacking. We analysed the profile of expression of the four Kv3 subunits by quantitative reverse transcription PCR and Western blot in the whole mouse brain and in dissected brain regions (olfactory bulb, septum, neocortex, hippocampus, brainstem and cerebellum) from 14 days after conception to 18 months after birth. In addition, we measured the levels of Kv3.1 and Kv3.4 messenger RNAs (mRNAs) and proteins in neocortex and hippocampus of APPPS1 mice, a transgenic model of Alzheimer's disease. Although all Kv3 transcripts were significantly expressed in embryonic age in whole brain extracts, only Kv3.1, Kv3.2 and Kv3.4 subunit proteins were present, suggesting a novel role for Kv3 channels at this developmental stage. With the exception of Kv3.4, during postnatal development, Kv3 transcripts and proteins showed a progressive increase in expression and reached an asymptote in adulthood, suggesting that the increase in Kv3 expression during development might contribute to the maturation of the electrical activity of neurons. During aging, Kv3 expression was rather stable. In contrast, in the neocortex of aged APPPS1 mice, Kv3.1 mRNA and protein levels were significantly lower compared to wild type, suggesting that a decrease in Kv3 currents could play a role in the cognitive symptoms of Alzheimer's disease.

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Decreased Rhythmic GABAergic Septal Activity and Memory-Associated θ Oscillations after Hippocampal Amyloid-β Pathology in the Rat

Cited by 97 publications

References 91 publications

Beta-amyloid induced changes in A-type K+ current can alter hippocampo-septal network dynamics

Beta-amyloid induced changes in A-type K+ current can alter hippocampo-septal network dynamics

Hippocampal network dynamics in response to α7 nACh receptors activation in amyloid-β overproducing transgenic mice

Brain Expression of Kv3 Subunits During Development, Adulthood and Aging and in a Murine Model of Alzheimer’s Disease

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