Activation of large-conductance Ca2+-activated K+ channels depresses basal synaptic transmission in the hippocampal CA1 area in APP (swe/ind) TgCRND8 mice

Ye, Hui; Jalini, Shirin; Mylvaganam, Shanthini; Carlen, Peter L.

doi:10.1016/j.neurobiolaging.2008.05.012

Cited by 57 publications

(42 citation statements)

References 69 publications

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“…Directly related to the present work, some studies have shown suppression in basal synaptic transmission and a severe impairment in LTP from TgCRND8 mice [7][8][9]. Our findings confirm and extend these previous reports regarding synaptic dysfunction in the hippocampus from TgCRND8 mice, which appears to have a strong correlation with progressive cognitive impairment in this mouse model of AD [9].…”

Section: Discussionsupporting

confidence: 93%

Carvedilol Reestablishes Long-Term Potentiation in a Mouse Model of Alzheimer's Disease

Arrieta‐Cruz

Wang

Pavlides

et al. 2010

JAD

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Abstract. In this study, we examined acute effects of carvedilol, a nonselective α/β-adrenergic receptor blocker, on neuronal transmission and long-term potentiation (LTP) in six month-old TgCRND8 mice and their wild-type age-matched controls. Field excitatory postsynaptic potentials were recorded in the CA1 region of the hippocampus from carvedilol-or vehicle dimethyl sulfoxide-treated slices, and differences in basal synaptic transmission and LTP were assessed. Carvedilol treatment produced a significant increase in basal synaptic transmission and LTP in TgCRND8 mice, as compared to their vehicle-treated slices, in which basal neuronal transmission and LTP decreased. Interestingly, carvedilol significantly suppressed spontaneous seizure activity in TgCRND8 mice as measured by the number of slices showing epileptic discharges as well as the number of spikes within these and the amplitude of the second spike, measured at baseline and end of recording. In contrast, vehicle-treated slices in TgCRND8 mice did not show a significant decrease in epileptic discharges. These results suggest that carvedilol reestablishes basal synaptic transmission, enhances neuronal plasticity and suppresses neuronal hyperexcitability in TgCRND8 mice.

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Section: Discussionsupporting

confidence: 93%

Carvedilol Reestablishes Long-Term Potentiation in a Mouse Model of Alzheimer's Disease

Arrieta‐Cruz

Wang

Pavlides

et al. 2010

JAD

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“…Disruption of neuronal excitability and abnormal AHP might contribute to neurodegeneration, in aging and AD brain (Ohno et al, 2004;Disterhoft and Oh, 2007;Driver et al, 2007;Ye et al, 2008). Transgenic mice overexpressing hAPPswe have an impairment of hippocampal gamma-frequency oscillations (Driver et al, 2007).…”

Section: Discussion Happ Expression In Rat Cortical Neurons Increasesmentioning

confidence: 99%

Expression of Human Amyloid Precursor Protein in Rat Cortical Neurons Inhibits Calcium Oscillations

Santos¹,

Pierrot²,

Morel³

et al. 2009

J. Neurosci.

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Synchronous calcium oscillations are observed in primary cultures of rat cortical neurons when mature networks are formed. This spontaneous neuronal activity needs an accurate control of calcium homeostasis. Alteration of intraneuronal calcium concentration is described in many neurodegenerative disorders, including Alzheimer disease (AD). Although processing of amyloid precursor protein (APP) that generates A␤ peptide has critical implications for AD pathogenesis, the neuronal function of APP remains unclear. Here, we report that expression of human APP (hAPP) in rat cortical neurons increases L-type calcium currents, which stimulate SK channels, calcium-dependent K ϩ channels responsible for medium afterhyperpolarization (mAHP). In a neuronal network, increased mAHP in some neurons expressing hAPP leads to inhibition of calcium oscillations in all the cells of the network. This inhibition is independent of production and secretion of A␤ and other APP metabolites. In a neuronal network, reduction of endogenous APP expression using shRNA increases the frequency and reduces the amplitude of calcium oscillations. Altogether, these data support a key role for APP in the control of neuronal excitability.

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“…Aβ acts as a neurotoxin causing neuronal dysfunction and apoptosis (Hardy and Higgins 1992) and synaptic plasticity impairment (Holscher et al 2007). Aβ may change the activity of various ionic channels in pyramidal neurons, e.g., L-type Ca 2+ channels (I Ca ) (Webster et al 2006); A-type fast-inactivating K + channels (I A ) and delayed rectifying K + channels (I K ) (Good et al 1996); large-conductance Ca 2+ -activated K + channels (I CT ) (Ye et al 2010;Chi and Qi 2006). In addition, Aβ can disturb the neuromodulators, (Tran et al 2002;Palop and Mucke 2010), which control memory encoding and recall (Hasselmo et al 1996).…”

Section: Introductionmentioning

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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Activation of large-conductance Ca2+-activated K+ channels depresses basal synaptic transmission in the hippocampal CA1 area in APP (swe/ind) TgCRND8 mice

Cited by 57 publications

References 69 publications

Carvedilol Reestablishes Long-Term Potentiation in a Mouse Model of Alzheimer's Disease

Carvedilol Reestablishes Long-Term Potentiation in a Mouse Model of Alzheimer's Disease

Expression of Human Amyloid Precursor Protein in Rat Cortical Neurons Inhibits Calcium Oscillations

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

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