Neuron–glia interactions in the rat supraoptic nucleus

https://doi.org/10.1016/S0079-6123(08)00410-XGet rights and content

Abstract

The adult hypothalamo-neurohypophysial system undergoes a striking activity-dependent morphological remodelling that modifies the glial enwrapping of its magnocellular neurons. Although the functional consequences of such remodelling remain hypothetical, recent evidence has provided new insights into the repercussions of glial environment modifications on the physiology of magnocellular neurosecretory cells at the synaptic level. These studies have revealed that the reduced astrocytic coverage of magnocellular neurons occurring in the SON affects various functions in which astrocytes play key roles. These functions include uptake of neurotransmitters such as glutamate, restricting diffusion of neuroactive substances within the extracellular space and release of informative molecules known as gliotransmitters that act on neighbouring neurons to modulate synaptic transmission and excitability. Overall, our observations indicate that the neuron–glial anatomical reorganization leads to modifications of glutamatergic transmission that might be important for the physiology of the hypothalamo-neurohypophysial system.

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.

References (39)

  • D.T. Theodosis

    Oxytocin-secreting neurons: a physiological model of morphological neuronal and glial plasticity in the adult hypothalamus

    Front. Neuroendocrinol.

    (2002)
  • J.S. Bains et al.

    Reciprocal interactions between CA3 network activity and strength of recurrent collateral synapses

    Nat. Neurosci.

    (1999)
  • L. Bonfanti et al.

    Radial glia-like cells in the supraoptic nucleus of the adult rat

    J. Neuroendocrinol.

    (1993)
  • C. Boudaba et al.

    Increased tonic activation of presynaptic metabotropic glutamate receptors in the rat supraoptic nucleus following chronic dehydration

    J. Physiol. (Lond.)

    (2003)
  • J.A. Cummings et al.

    Ca2+ signaling requirements for long-term depression in the hippocampus

    Neuron

    (1996)
  • N.C. Danbolt

    Glutamate uptake

    Prog. Neurobiol.

    (2000)
  • M. El Majdoubi et al.

    Activity-dependent morphological synaptic plasticity in an adult neurosecretory system: magnocellular oxytocin neurons of the hypothalamus

    Biochem. Cell. Biol.

    (2000)
  • G.R. Gordon et al.

    Norepinephrine triggers release of glial ATP to increase postsynaptic efficacy

    Nat. Neurosci.

    (2005)
  • P.G. Haydon et al.

    Astrocyte control of synaptic transmission and neurovascular coupling

    Physiol. Rev.

    (2006)
  • Cited by (39)

    • Emerging role of astrocytes in oxytocin-mediated control of neural circuits and brain functions

      2022, Progress in Neurobiology
      Citation Excerpt :

      Thus, a reduction in the clearance rate inevitably results in an increased extracellular concentration of neurotransmitters, which ultimately results in an amplification of post-synaptic currents. Moreover, the neurotransmitters can spill over the synaptic cleft and activate presynaptic (e.g. mGluRs) or extrasynaptic (e.g. NMDA) receptors to promote a feedback regulatory effect or to modulate the efficiency/potency of neighboring synapses (Oliet et al., 2008). Third, the retraction of astrocytic processes may declutter the extracellular space, allowing the formation of new synapses, as suggested for the hypothalamus (Hatton et al., 1984) (For a more general review on the effects of astrocytes morphological modification, see Lawal et al., 2022).

    • Models in neuroendocrinology

      2018, Mathematical Biosciences
    • The Neurobiology of D-Serine Signaling

      2018, Advances in Pharmacology
    • Physiological mechanisms, behavioral and psychological factors influencing the transfer of milk from mothers to their young

      2016, Hormones and Behavior
      Citation Excerpt :

      For example, Hatton and his colleagues have documented both increased dendritic bundling and a higher frequency of tight junctions in OT neurons during lactation (Hatton et al., 1992; Wang and Hatton, 2009). In addition, Theodosis and her colleagues have demonstrated that withdrawal of glial processes from around the cell bodies of oxytocinergic neurons in the PVN and SON that occurs in response to the hormonal profile of late pregnancy results in an increase in synaptic input to these cells (Oliet et al., 2008; Theodosis et al., 1986). There are also changes in the neurochemical content of magnocellular cells during lactation such that expression of nitric oxide synthase increases in OT cells (Popeski et al., 1999, 2003) and some magnocellular cells that previously expressed only vasopressin express OT (Kiss, 1988).

    • Central Nervous System Control of Oxytocin Secretion during Lactation

      2015, Knobil and Neill's Physiology of Reproduction: Two-Volume Set
    View all citing articles on Scopus
    View full text