The hypothalamus is the single most important integrator of vegetative and endocrine regulation in the body
Neuroendocrine secretory neurons establish a permanent dialogue with hypothalamic glial cells to maintain body homeostasis
Hypothalamic astrocytes control the extracellular levels of neurotransmitters and neuromodulators in the neuroendocrine networks regulating body homeostasis
Hypothalamic tanycytes control both neuroendocrine secretions and the access of key peripheral homeostatic signals into the brain
The recognition of the clinical relevance of glia–neuron interactions in the hypothalamus might pave the way for the development of new treatment strategies in the central loss of body homeostasis in human syndromes
Natural fluctuations in physiological conditions require adaptive responses involving rapid and reversible structural and functional changes in the hypothalamic neuroendocrine circuits that control homeostasis. Here, we discuss the data that implicate hypothalamic glia in the control of hypothalamic neuroendocrine circuits, specifically neuron–glia interactions in the regulation of neurosecretion as well as neuronal excitability. Mechanistically, the morphological plasticity displayed by distal processes of astrocytes, pituicytes and tanycytes modifies the geometry and diffusion properties of the extracellular space. These changes alter the relationship between glial cells of the hypothalamus and adjacent neuronal elements, especially at specialized intersections such as synapses and neurohaemal junctions. The structural alterations in turn lead to functional plasticity that alters the release and spread of neurotransmitters, neuromodulators and gliotransmitters, as well as the activity of discrete glial signalling pathways that mediate feedback by peripheral signals to the hypothalamus. An understanding of the contributions of these and other non-neuronal cell types to hypothalamic neuroendocrine function is thus critical both to understand physiological processes such as puberty, the maintenance of bodily homeostasis and ageing and to develop novel therapeutic strategies for dysfunctions of these processes, such as infertility and metabolic disorders.
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This work was supported by the Agence National pour la Recherche (ANR) grant number ANR-15-CE14-0025. Jerome Clasadonte was supported by the Horizon 2020 Marie Skłodowska-Curie actions — European Research Fellowship (H2020-MSCA-IF-2014, ID656657). The authors are indebted to Dr Rasika for editing the manuscript and to the European consortium studying GnRH biology (COST Action BM1105) coordinated by Dr Nelly Pitteloud for insightful discussions.
The authors declare no competing financial interests.
Neural lobe (or posterior lobe) of the pituitary, where the unmyelinated axons of the magnocellular secretory neurons of the supraoptic and paraventricular hypothalamic nuclei project and release oxytocin and vasopressin directly into the general circulation for delivery to target tissues. In this protrusion of the brain, the neuroendocrine terminals of those secretory neurons interact closely with pituicytes that modulate their direct access to the pericapillary space.
- Tonic activation
Persistent membrane receptor activation resulting from the random and sustained release of transmitters in the extracellular space. Tonic activation is opposed to phasic activation, a transient membrane receptor activation resulting from a more spatially and temporally discrete release of transmitters in the synaptic cleft.
- Glial coverage
Degree of ensheathment (physical apposition) of a synapse or a soma by peripheral astrocytic processes.
- GABA transporters
Transporters that are involved in the synaptic reuptake of GABA.
- Vesicular GABA transporters
Transporters that are involved in the vesicular packaging of GABA.
- Heterosynaptic crosstalk
Dialogue between two synapses of different natures, in which the activity of one influences the other.
- Photoperiodic changes
Annual changes (homeostatic process) that occur in seasonal species based on day length in order to adapt to seasonal cycles.
- En passant
Of synapses, contacts established with axons or cell bodies along the trajectory of neural cell processes targeting deeper tissue structures.
Members of a family of secreted guidance molecules known to control the embryonic migration of neurons secreting gonadotropin-releasing hormone.
- Parenchymatous basal lamina
Basement membrane delimitating the surface of the brain tissue. In the median eminence, the parenchymatous basal lamina delineates the pericapillary space the secretory neuroendocrine terminals about to release their neurohormone into the hypothalamic–pituitary portal blood system.
- Vimentin-immunoreactive processes
Cellular extensions rich in vimentin, an intermediate filament protein that is selectively expressed in classical ependymal cells with beating cilia and tanycytes in vivo. Vimentin immunoreactivity heavily decorates the long and slender extensions sent by tanycytes towards the nervous parenchyma and hence is a good marker of tanycytic processes.
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Clasadonte, J., Prevot, V. The special relationship: glia–neuron interactions in the neuroendocrine hypothalamus. Nat Rev Endocrinol 14, 25–44 (2018). https://doi.org/10.1038/nrendo.2017.124
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