Extensive astrocyte synchronization advances neuronal coupling in slow wave activity in vivo

Abstract

Slow wave activity (SWA) is a characteristic brain oscillation in sleep and quiet wakefulness. Although the cell types contributing to SWA genesis are not yet identified, the principal role of neurons in the emergence of this essential cognitive mechanism has not been questioned. To address the possibility of astrocytic involvement in SWA, we used a transgenic rat line expressing a calcium sensitive fluorescent protein in both astrocytes and interneurons and simultaneously imaged astrocytic and neuronal activity in vivo. Here we demonstrate, for the first time, that the astrocyte network display synchronized recurrent activity in vivo coupled to UP states measured by field recording and neuronal calcium imaging. Furthermore, we present evidence that extensive synchronization of the astrocytic network precedes the spatial build-up of neuronal synchronization. The earlier extensive recruitment of astrocytes in the synchronized activity is reinforced by the observation that neurons surrounded by active astrocytes are more likely to join SWA, suggesting causality. Further supporting this notion, we demonstrate that blockade of astrocytic gap junctional communication or inhibition of astrocytic Ca2+ transients reduces the ratio of both astrocytes and neurons involved in SWA. These in vivo findings conclusively suggest a causal role of the astrocytic syncytium in SWA generation.

Copper signalling: causes and consequences

“…4 . ) [ 6 , 22 , 80 , 179 , 180 , 233 , 234 , 236 – 243 , 245 , 254 , 255 , 336 , 339 , 340 , 342 – 362 ]. GABA can be synthesized from the pA putrescine by copper-containing CuAO in astrocytes.…”

“…The increased GABA release and the generated tonic inhibition thereby modulate the power of gamma range oscillation in the CA1 region in vivo. The concentration of cytosolic and extracellular putrescine has been determined to be 22 nmol/g and 12 nmol/g , respectively [ 339 ]. In contrast, copper may decrease tonic inhibition via acting on delta subunit-containing extrasynaptic GABA A receptors [ 235 , 237 , 246 ], thus adding a new layer to disinhibitory mechanisms in copper-rich brain areas.…”

“…The proposed scheme conjectures activity-dependent changes of copper pools [ 179 , 180 ] and polyamines (pAs), produced by CuAOs in astrocytes. First, an enhanced gap junction communication can be achieved by pAs [ 356 – 358 ], possibly promoting activity-dependent synchronization [ 339 , 359 ]. Second, major inhibitory neurotransmitter gamma-aminobutyric acid (GABA) formed from pAs is released by astrocyte-specific GABA transporter [ 360 ].…”

Subcortical theta oscillations alternate with high amplitude neocortical population within synchronized states

“…Glia are also known to be involved in homeostatic processes during sleep (Bjorness et al, 2016; Clinton, Davis, Zielinski, Jewett, & Krueger, 2011; de Andrés, Garzón, & Reinoso-Suárez, 2011b; Fellin, Ellenbogen, De Pittà, Ben-Jacob, & Halassa, 2012; Poskanzer & Yuste, 2011). Furthermore, recent work with calcium imaging shows heavy glial involvement prior to neuronal involvement during SWA (Szabó et al, 2017). Therefore, BL5 may include glia.…”

Amyloid pathology disrupts gliotransmitter release in astrocytes

“…Increased astrocytic synchronization in the form of coherent Ca 2+ and gliotransmitter release events boosts neural synchrony in vivo and ex vivo 79,80 . Synchronous Ca 2+ activity in astrocytes is also associated with pathological neuronal discharges in several disease models including epilepsy and AD 14,81 .…”