Acute intracerebral treatment with amyloid-beta (1–42) alters the profile of neuronal oscillations that accompany LTP induction and results in impaired LTP in freely behaving rats

Abstract

Accumulation of amyloid plaques comprises one of the major hallmarks of Alzheimer’s disease (AD). In rodents, acute treatment with amyloid-beta (Aβ; 1–42) elicits immediate debilitating effects on hippocampal long-term potentiation (LTP). Whereas LTP contributes to synaptic information storage, information is transferred across neurons by means of neuronal oscillations. Furthermore, changes in theta-gamma oscillations, that appear during high-frequency stimulation (HFS) to induce LTP, predict whether successful LTP will occur. Here, we explored if intra-cerebral treatment with Aβ(1–42), that prevents LTP, also results in alterations of hippocampal oscillations that occur during HFS of the perforant path-dentate gyrus synapse in 6-month-old behaving rats. HFS resulted in LTP that lasted for over 24 h. In Aβ-treated animals, LTP was significantly prevented. During HFS, spectral power for oscillations below 100 Hz (δ, θ, α, β and γ) was significantly higher in Aβ-treated animals compared to controls. In addition, the trough-to-peak amplitudes of theta and gamma cycles were higher during HFS in Aβ-treated animals. We also observed a lower amount of envelope-to-signal correlations during HFS in Aβ-treated animals. Overall, the characteristic profile of theta-gamma oscillations that accompany successful LTP induction was disrupted. These data indicate that alterations in network oscillations accompany Aβ-effects on hippocampal LTP. This may comprise an underlying mechanism through which disturbances in synaptic information storage and hippocampus-dependent memory occurs in AD.

Optogenetic activation of SST-positive interneurons restores hippocampal theta oscillation impairment induced by soluble amyloid beta oligomersin vivo

“…Reduction in theta oscillation power has also been observed in other genetically modified AD mice models such as 3xTg (Mondragon-Rodriguez et al, 2018), CRND8 (Goutagny et al, 2013), and APP23 transgenic AD mice models (Ittner et al, 2014). However, in addition to the reduction of theta oscillation power, hypersynchrony and epileptic activities were also observed in transgenic AD mice models (Bezzina et al, 2015; Ittner et al, 2014; Palop and Mucke, 2010) which was absent in the AβO-injected mice in ours and other studies (Kalweit et al, 2015). Hence, long-term effects of AβO may cause differing effects on the hippocampal neural circuits, which will require further investigation.…”

“…In our study, we injected AβO into the hippocampus to create AβO pathology in vivo , a method adopted in many studies investigating the impact of AβO physiological and cognitive functions (Balducci et al, 2010; Brouillette et al, 2012; Cetin and Dincer, 2007; Faucher et al, 2015; Kalweit et al, 2015; Kim et al, 2014b; Nicole et al, 2016; Orban et al, 2010; Villette et al, 2010; Yi et al, 2018). After three weeks of recovery following AβO injection in SST-Cre and PV-Cre mice, we observed a significant reduction in peak power of theta oscillations across all hippocampal sublayers compared to that in control SST-Cre and PV-Cre mice (Fig.…”

“…AβOs have deleterious effects on neurons and synapses, causing synaptic dysfunction (Lacor et al, 2004; Shankar et al, 2008) and neural death (Alberdi et al, 2010; De Felice et al, 2007; Decker et al, 2010). Experimentally, AβO have been injected into the hippocampus in vivo to investigate the effect of AβO in hippocampal network oscillations, synaptic plasticity, and behavioral memory performance (Kalweit et al, 2015; Kim et al, 2014b; Nicole et al, 2016; Orban et al, 2010; Villette et al, 2010; Yi et al, 2018). In these studies, hippocampal theta oscillation, which is important in providing a clock mechanism for spike phase coding in spatial information processing (Dragoi and Buzsaki, 2006; Lisman and Jensen, 2013; O’Keefe and Recce, 1993) and support synaptic plasticity (Bikbaev and Manahan-Vaughan, 2008; Buzsaki, 2002; Huerta and Lisman, 1993; Nyhus and Curran, 2012; Tsanov and Manahan-Vaughan, 2009), was impaired in AD by showing decreased power compared to normal conditions.…”

Neurodegeneration-related beta-amyloid as autocatabolism-attenuator in amicro-in vivosystem

“…The concentrations of the stock solutions were 1 mg/mL in distilled water; the aggregation time was 3h (25 °C, pH 3.5); the neutralization (to pH 7.5) was performed with NaOH (1 N). (Kalweit et al, 2015) The final concentrations of Aβ were 100 µg/mL. The standard medium content (mg/L) were: Ca 2+ 31.05; Mg 2+ 17.6; Na + 0.9; K + 0.25; Fe 2+ 0.001; HCO3 -153.097; SO4 -3; Cl -0.8; F -0.02; H2SiO3 3.3 (pH=7.5).…”

Multivalent foldamer-based affinity assay for selective recognition of Aβ oligomers

“…The Aβ solutions with different aggregation state were prepared according to literature protocols. [36,39] …”