Morphological and physiological interactions of NG2‐glia with astrocytes and neurons

Abstract

Models of central nervous system (CNS) function have historically been based on neurons and their synaptic contacts -the neuronal doctrine. This doctrine envisages glia as passive supportive cells. However, electrophysiological and imaging studies in brain slices show us that astrocytes, the most numerous cells in the brain, express a wide range of neurotransmitter receptors that are activated in response to synaptic activity. Furthermore, astrocytes communicate via calcium signals that are propagated over long distances by the release of 'gliotransmitters', the most abundant being adenosine triphosphate (ATP). This has led to the concept of the neuron-astroglial functional unit as the substrate of integration in the CNS. Recently, a novel glial cell type has been characterized by expression of the proteoglycan NG2. These NG2-glia receive presynaptic input from neurons and responds to neurotransmitters released at synapses. Now, studies on transgenic mice in which fluorescent proteins are specifically expressed by subclasses of glia are helping to address the question of where NG2-glia fit in the neuron-astroglial model of integrated brain function. NG2-glia, as well as astrocytes, have been shown to respond to neuronal and astroglial signals by raised intracellular calcium, which is a potential communications mechanism by which NG2-glia may be active partners in neuron-glial circuits. Moreover, a current concept of NG2-glia considers them to be 'neural stem cells' and an exciting prospect is that neuron-glial signalling may regulate the differentiation capacity of NG2-glia and their response to injury.

Abstinence From Moderate Alcohol Self‐Administration Alters Progenitor Cell Proliferation and Differentiation in Multiple Brain Regions of Male and Female P Rats

“…It is possible that this increase in NG 2 + expressing cells represents the recovery of myelination upon abstinence. Interestingly, NG 2 + cells have recently been found to have a broader potential than just oligodendrocyte precursors (Wigley et al, 2007). NG 2 + cells have recently been found be uniquely different from standard adult neurons and astrocytes.…”

“…NG 2 + cells have recently been found be uniquely different from standard adult neurons and astrocytes. They integrate as functional neuron-glial cells that respond to synaptic transmission and changes in long-term potentiation (LTP) representing a new type of signaling progenitor cell that can also form new neurons (Wigley et al, 2007). Although the exact functional roles of NG 2 + cells remain unknown, at least some of them in mature brain are generally considered as the precursors of oligodendrocytes (Levine et al, 2001;Levison et al, 1999;Peters, 2004;Stallcup, 2002), which could contribute partially to the restoration of myelination in the cingulum upon abstinence.…”

Analysis of Astroglial K+ Channel Expression in the Developing Hippocampus Reveals a Predominant Role of the Kir4.1 Subunit

“…Based on initial recordings in acute hippocampal brain slices, glial cells with predominating passive and "complex" current patterns have been distinguished (Steinhäuser et al, 1994), and later work has established that passive cells represent bona fide astrocytes whereas complex cells constitute a different cell type (termed GluR cells or NG2 glia) (Matthias et al, 2003;Wigley et al, 2007). However, it is still unclear which ion channel(s), in addition to Kir4.1, underlies the passive currents of astrocytes in the hippocampus.…”

Dividing glial cells maintain differentiated properties including complex morphology and functional synapses

“…Importantly, NG2 cells receive synaptic inputs from neurons (10)(11)(12)(13)(14), and the neuron-NG2 glia synapses can undergo activitydependent modification analogous to long-term potentiation (11), a hallmark of the cellular mechanism underlying learning and memory (15). NG2 cells also make contact with nodes of Ranvier (16) in the white matter and hence are capable of responding to or modulating neuronal activity in a manner perhaps similar to the function of astrocytes (17). Given the unique morphological, physiological, and functional properties of NG2 cells, which are widely distributed in the adult brain, they are now recognized as a distinct, differentiated, macroglial cell population (18,19).…”