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Ca2+ ions can trigger the release of two important neurotransmitters: glutamate and ATP (adenosine triphosphate). The release mechanism could be via hemichannels (HC) or exocytosis (Orellana and Stehberg, 2014). After being released, glutamate and ATP can affect the excitability of neighboring neurons (Figure 5-6).
Glutamate is an excitatory neurotransmitter, capable of opening NMDA receptors, allowing Na+ and Ca2+ ions to flow into the neuron, resulting in membrane depolarization. Glutamate release from astrocytes can even cause synchronized firing in surrounding neurons (Carmignoto and Fellin, 2006). On the other hand, glutamate can also activate the G protein-coupled receptor mGluR (Chapter 6) located either on astrocytes or adjacent neurons. Activation of mGluR may cause more Ca2+ ions to enter the cytosol from ER, thereby releasing even more glutamate and ATP. As a result, the neuronal excitability varies with the calcium wave which oscillates at infra-slow frequency.
The released ATP may break down into adenosine, which can lead to the opening of a special type of potassium channels known as GIRK channels. The opening of GIRK channels allows K+ ions to flow outward, reducing membrane potential. Hence, the opening of GIRK channels has inhibitory effects on neuronal firing, counteracting glutamate's excitatory effects. Figure 5-6 does not show the interaction between adenosine and GIRK channels. Its details will be discussed in Chapter 6.
Infra-slow oscillations (ISO) are very common. Not only do they appear in the brain's resting state networks, the blood vessel contraction and hemoglobin concentration also vary at the frequency around 0.1 Hz (Rayshubskiy et al., 2014), the depth of breathing fluctuates periodically at the frequency of 0.03 Hz (Birn et al., 2008), even the stomach may generate ISO (Richter et al., 2016). From the above discussion, we can understand that neurons coupled with astrocytes will oscillate at the infra-slow frequency, but how do they synchronize? The mechanism of neural synchrony in a local area has been well understood (see this article). However, ISO involves widely distributed brain regions, whose synchronization mechanism remains unclear. A possible mechanism is discussed in Section 10.5.
Global synchronization is required for the coordination among various brain areas. For instance, the alpha waves originate from at least two different areas: thalamus and anterior cingulate cortex (ACC), propagating to posterior and anterior parts of the brain, respectively (Connemann et al., 2005; Schreckenberger et al., 2004). Synchronization between the two sources could be crucial for the emergence of consciousness, as disruption of the anterior-posterior functional connectivity can cause unconsciousness (Section 5.1). Another example is the binding problem discussed in Section 4.5. The global synchronization of ISO can facilitate the binding of information that is being processed at various brain areas. Further details are presented in the next two sections.