Glutamate-mediated bi-directional signaling between neurons and astrocytes

Abstract

Functional plasticity is an important property of the central nervous system (CNS). A major site for this plasticity is at the chemical synapse. Here, neurons and astrocytes intermingle forming a morphologically intimate relationship (Chapters 3 and 4) where astrocytes are favorably positioned to exchange signals with neurons (Figure 15.1). Ca²⁺ entry though voltage-gated channels into the presynaptic terminal signals to the secretory machinery, which allows the release of neurotransmitter stored in synaptic vesicles into the synaptic cleft. Released neurotransmitter then signals to the postsynaptic neuron by activating its receptors (Figure 15.1, arrow 1). Under certain circumstances, neurotransmitter can ‘spillover’ from the synaptic cleft and reach neurotransmitter receptors in adjacent astrocytes (Figure 15.1, arrow 2), eliciting astrocytic increases in intracellular Ca²⁺ ion concentration [Ca²⁺]_i. These evoked and/or spontaneous elevations of [Ca²⁺]_i in astrocytes can cause the release of a neurotransmitter, e.g., glutamate, from astrocytes, which signals to the presynaptic nerve terminal to modulate synaptic neurotransmission and/or released glutamate can affect postsynaptic cells (Figure 15.1, arrows 3 and 4). Additional signaling can occur between astrocytes in the form of intercellular Ca²⁺ waves (Figure 15.1, arrows 5; Chapters 12-14). In this chapter the focus is on glutamate-mediated bi-directional signaling between neurons and astrocytes.