Astrocytic modulation of cortical oscillations

Abstract

Brain waves are rhythmic voltage oscillations emerging from the synchronization of individual neurons into a neuronal network. These oscillations range from slow to fast fluctuations, and are classified by power and frequency band, with different frequency bands being associated with specific behaviours. It has been postulated that at least ten distinct mechanisms are required to cover the frequency range of neural oscillations, however the mechanisms that gear the transition between distinct oscillatory frequencies are unknown. In this study, we have used electrophysiological recordings to explore the involvement of astrocytic K+ clearance processes in modulating neural oscillations at both network and cellular levels. Our results indicate that impairment of astrocytic K+ clearance capabilities, either through blockade of K+ uptake or astrocytic connectivity, enhance network excitability and form high power network oscillations over a wide range of frequencies. At the cellular level, local increases in extracellular K+ results in modulation of the oscillatory behaviour of individual neurons, which underlies the network behaviour. Since astrocytes are central for maintaining K+ homeostasis, our study suggests that modulation of their inherent capabilities to clear K+ from the extracellular milieu is a potential mechanism to optimise neural resonance behaviour and thus tune neural oscillations.

Soft Ring‐Shaped Cellu‐Robots with Simultaneous Locomotion in Batches

“…The ring‐shaped brain surrogate can also biosense and respond to GABAergic inhibitor picrotoxin and neurotransmitter glutamate with a longer response time in the middle of the cellular aggregate but shorter response time at the edge positions (Figure M), which can be explained by the mass transfer of external chemicals (Video S7, Supporting Information). Our coculture brain surrogate had a calcium oscillation rate of 125 Hz, which is close to the native brain slice with an oscillation frequency of 130 mHz . We observed the increase in spiking amplitude and decrease in frequency (38 mHz) after picrotoxin addition, and a steep hoist of fluorescent intensity after glutamate addition (Figure M).…”

“…Our coculture brain surrogate had a calcium oscillation rate of 125 Hz, which is close to the native brain slice with an oscillation frequency of 130 mHz. [39] We observed the increase in spiking amplitude and decrease in frequency (38 mHz) after picrotoxin addition, and a steep hoist of fluorescent intensity after glutamate addition ( Figure 4M). The transient ascent in fluorescence intensity upon glutamate addition of cell 3 and 4 in Figure 4M suggests that these cells are astrocytes, which are mainly distributed at the inner side of the ring structure.…”

Neuromodulation of astrocytic K+ clearance

“…Due to the absence of a selective blocker for astrocytic Na+/K+ ATPase, and our interest in assessing K+ uptake into astrocytes via Kir channels, these measurements were performed at room temperature (22oC), when Na+/K+ ATPase activity is fairly low. Various KCl concentrations, corresponding to low (~5 mM), high (~15 mM) and excessive (~30 mM), were added to physiological aCSF and locally applied at a constant distance (~10 µm) from the K+-selective microelectrode through a puffing pipette (tip diameter of 1 μm) for 0.1 sec, as previously described (Bellot-Saez et al, 2018). Preparation and calibration of the K+-selective microelectrodes were performed as detailed in (Deveau et al, 2005;Haack & Rose, 2014).…”

“…To selectively block K + spatial buffering through the astrocytic network, we incubated the slices with a mixture of connexin-43 (Cx43) mimetic peptides 300μM), that selectively decrease astrocytic connectivity via electrical GJs (Bellot-Saez et al, 2018). Indeed, selective blockade of Cx43 significantly reduced the K+ clearance rate (F(1, 82) = 58.54, p < 0.0001, two-way ANOVA).…”

“…To do so, animals are constantly switching between behavioral states, which are correlated to different network oscillations. We recently showed that local alterations in the extracellular K+ concentration ([K+]o) can affect the oscillatory activity of neuronal networks (Buskila et al, 2019) and that specific impairments of the astrocytic clearance mechanism can affect the resonance and oscillatory behaviour of neurons both at single cell and network levels (Bellot-Saez et al, 2018), implying that astrocytes can modulate neuronal network activity. However, the cellular and molecular mechanisms that affect this clearance process by astrocytes are still unknown.…”