Neuron–glia interactions in the rat supraoptic nucleus
Introduction
The hypothalamo-neurohypophysial system is a neuroendocrine system essential for animal survival. It is composed of magnocellular neurons located in the paraventricular (PVN) and supraoptic (SON) nuclei. These neurons synthesize the hormones oxytocin (OXT) and vasopressin (AVP) (Swaab et al., 1975). Whereas OXT plays a key role in reproductive functions like parturition and lactation, AVP is essential to body fluid and cardiovascular homoeostasis (Poulain and Wakerley, 1982). Magnocellular neurons send their axons to the neurohypophysis where OXT and AVP are secreted directly in the blood stream. In addition, these peptides can be released centrally in various brain regions including within the PVN and SON (Ludwig and Pittman, 2003) where they exert local regulatory actions (Kombian et al., 2002; Ludwig et al., 2002; Oliet et al., 2007). OXT and AVP secretion depends on the electrical activity of magnocellular neurons which is itself under the influence of excitatory glutamatergic and inhibitory GABAergic synaptic afferent inputs (Leng et al., 1999; El Majdoubi et al., 2000).
Under basal conditions of secretion, like in virgin rats, OXT neurons often occur in tightly packed clusters. In spite of their tight apposition, they are separated by neuropil elements including fine lamella-like processes of astrocytic origin (Theodosis, 2002). Interestingly, under conditions of strong neurohypophysial hormone secretion, such as during chronic dehydration, parturition and lactation, the hypothalamo-neurohypophysial system, and in particular its oxytocinergic portion, undergoes a remarkable anatomical remodelling that is reversible upon cessation of the stimulation (Myiata and Hatton, 2002; Theodosis, 2002). This remodelling is primarily characterized by a pronounced reduction of the astrocytic coverage of neurons and synapses. Thus, under certain physiological conditions, a diminished astrocytic coverage of neurons and synapses may impact the magnocellular system in view of the different functions ensured by glial cells in the central nervous system.
Work performed during the last decade has revealed that glial cells were an active component of the chemical synapse, leading to the emerging concept of the tripartite synapse (Volterra and Meldolesi, 2005; Haydon and Carmignoto, 2006). Among the different roles played by astrocytes, it is well admitted that they represent physical barrier to diffusion in the extracellular space (Syková, 2001) and that they are responsible for the clearance of neurotransmitters like glutamate and GABA (Schousboe, 2003). Furthermore, glial cells can detect synaptic activity through the expression of specific receptors at their surface whose stimulation can lead to the release of signalling molecules named gliotransmitters by analogy to neurotransmitters. In view of these functions, the change in glial environment might impact the concentration and range of action of both neuro- and glio-transmitters in the SON.
Three types of astrocytes are present in the SON. There are typical stellate astrocytes found interspersed in the nucleus (Montagnese et al., 1988; Bonfanti et al., 1993). The most numerous are radial-like astrocytes whose cell bodies are located in the ventral part of the nucleus. These cells send long processes oriented ventro-dorsally through the nucleus (Bonfanti et al., 1993). The last type of astrocytes, found in the ventral glia lamina (VGL) close to the subarachnoid space, is characterized by small and round cell bodies with few processes (Salm, 2000; Israel et al., 2003). Recent electrophysiological analyses performed in lactating and dehydrated animals have investigated the consequences of astroglial remodelling onto synaptic transmission in the SON and PVN (Oliet et al., 2001; Boudaba et al., 2003; Piet et al., 2004; Gordon et al., 2005; Panatier et al., 2006). Here, we will review the results obtained in lactating and dehydrated rats and their putative repercussions for the physiology of the hypothalamo-neurohypophysial system.
Section snippets
Diffusion properties in the SON
Clearance of neurotransmitters depends on degradation, uptake and diffusion. Indeed, fine astrocytic processes hinder diffusion of molecules in the extracellular space (Syková, 2001). Glial wrapping of synapses and neuronal elements is therefore likely to limit the amount of transmitter escaping from the synaptic cleft, a phenomenon known as “spillover”. As a consequence, the astrocytic environment of neurons appears to govern crosstalk between adjacent synapses and intercellular communication
Glial contribution to glutamatergic and GABAergic transmission in the SON
Besides the key role played by astrocytes in hindering the diffusion of molecules in the extracellular space, astrocytes play a prominent role in the clearance of synaptically-released glutamate (Danbolt, 2000). This is ensured thanks to the high-affinity glutamate transporters GLT-1 and GLAST located on their plasma membrane. There is compelling evidence indicating that astrocytic GLT-1 subtype of transporter is responsible for most, if not all, of the uptake of synaptically-released glutamate
Gliotransmission in the SON and modulation of NMDA receptors
It is now acknowledged that glial cells can modulate synaptic transmission by releasing gliotransmitters (Volterra and Meldolesi, 2005; Haydon and Carmignoto, 2006). One of them is d-serine, a d-amino acid acting as a ligand at the glycine-binding site of NMDA receptors (NMDARs). This is of strong relevance for the central nervous system since NMDA receptors play an important role in fast excitatory transmission and long-term synaptic plasticity. NMDAR activation depends on the binding of
Conclusions
Taken together, the data reviewed here, provide new insights on the functional consequences of the anatomical remodelling occurring in the SON during lactation or chronic dehydration. In particular, modification of the astrocytic environment of neurons appears to modify both synaptic and extrasynaptic transmission mediated by glutamate. This is directly related to the presence on glial cells of transporters that clear away the excitatory amino acid and to the fact that fine astrocytic processes
Abbreviations
- AVP
Vasopressin
- dAAO
d-amino acid oxidase
- GABA
gamma-aminobutyric acid
- GO
glycine oxidase
- LTD
long-term depression
- LTP
long-term potentiation
- mGluR
metabotropic glutamate receptor
- NMDA
n-methyl-d-aspartic acid
- OXT
oxytocin
- PVN
paraventricular nucleus
- SON
supraoptic nucleus
- TMA+
tetramethylammonium
- VGL
ventral glia lamina
Acknowledgements
Work in the authors’ laboratory is supported in part by grants from Inserm, Human Frontier Science Program, ANR, FRC and the Conseil Régional d’Aquitaine. SHRO is the recipient of a NARSAD independent investigator award. Aude Panatier and Richard Piet were funded by studentships from the French Ministry of Education and Research.
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