Neuronal lipid droplets play a conserved and sex-biased role in maintaining whole-body energy homeostasis.

Lipids are essential for neuron development and physiology. Yet, the central hubs that coordinate lipid supply and demand in neurons remain unclear. Here, we combine invertebrate and vertebrate models to establish the presence and functional significance of neuronal lipid droplets (LD) .

A conceptual framework for astrocyte function.

The participation of astrocytes in brain computation was hypothesized in 1992, coinciding with the discovery that these cells display a form of intracellular Ca signaling sensitive to neuroactive molecules. This finding fostered conceptual leaps crystalized around the idea that astrocytes, once thought to be passive, participate actively in brain signaling and outputs. A multitude of disparate roles of astrocytes has since emerged, but their meaningful integration has been muddied by the lack of consensus and models of how we conceive the functional position of these cells in brain circuitry.

A genetically encoded fluorescent biosensor for extracellular L-lactate.

L-Lactate, traditionally considered a metabolic waste product, is increasingly recognized as an important intercellular energy currency in mammals. To enable investigations of the emerging roles of intercellular shuttling of L-lactate, we now report an intensiometric green fluorescent genetically encoded biosensor for extracellular L-lactate. This biosensor, designated eLACCO1.

Obesity-induced astrocyte dysfunction impairs heterosynaptic plasticity in the orbitofrontal cortex.

Overconsumption of highly palatable, energy-dense food is considered a key driver of the obesity pandemic. The orbitofrontal cortex (OFC) is critical for reward valuation of gustatory signals, yet how the OFC adapts to obesogenic diets is poorly understood. Here, we show that extended access to a cafeteria diet impairs astrocyte glutamate clearance, which leads to a heterosynaptic depression of GABA transmission onto pyramidal neurons of the OFC.

Whole brain irradiation in mice causes long-term impairment in astrocytic calcium signaling but preserves astrocyte-astrocyte coupling.

Whole brain irradiation (WBI) therapy is an important treatment for brain metastases and potential microscopic malignancies. WBI promotes progressive cognitive dysfunction in over half of surviving patients, yet, the underlying mechanisms remain obscure. Astrocytes play critical roles in the regulation of neuronal activity, brain metabolism, and cerebral blood flow, and while neurons are considered radioresistant, astrocytes are sensitive to γ-irradiation.

Author Correction: Stress gates an astrocytic energy reservoir to impair synaptic plasticity.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Stress gates an astrocytic energy reservoir to impair synaptic plasticity.

Astrocytes support the energy demands of synaptic transmission and plasticity. Enduring changes in synaptic efficacy are highly sensitive to stress, yet whether changes to astrocyte bioenergetic control of synapses contributes to stress-impaired plasticity is unclear. Here we show in mice that stress constrains the shuttling of glucose and lactate through astrocyte networks, creating a barrier for neuronal access to an astrocytic energy reservoir in the hippocampus and neocortex, compromising long-term potentiation.

Stress-induced structural and functional modifications of astrocytes-Further implicating glia in the central response to stress.

An organism's response to stress requires activation of multiple brain regions. This can have long-lasting effects on synaptic transmission and plasticity that likely provide adaptive benefits. Recent evidence implicates not only neurones, but also glial cells in the regulation of the central response to stress.

Cholecystokinin Switches the Plasticity of GABA Synapses in the Dorsomedial Hypothalamus via Astrocytic ATP Release.

Whether synapses in appetite-regulatory brain regions undergo long-term changes in strength in response to satiety peptides is poorly understood. Here we show that following bursts of afferent activity, the neuromodulator and satiety peptide cholecystokinin (CCK) shifts the plasticity of GABA synapses in the dorsomedial nucleus of the hypothalamus of male Sprague Dawley rats from long-term depression to long-term potentiation (LTP). This LTP requires the activation of both type 2 CCK receptors and group 5 metabotropic glutamate receptors, resulting in a rise in astrocytic intracellular calcium and subsequent ATP release.

Dynamics of surface neurotransmitter receptors and transporters in glial cells: Single molecule insights.

The surface dynamics of neurotransmitter receptors and transporters, as well as ion channels, has been well-documented in neurons, revealing complex molecular behaviour and key physiological functions. However, our understanding of the membrane trafficking and dynamics of the signalling molecules located at the plasma membrane of glial cells is still in its infancy. Yet, recent breakthroughs in the field of glial cells have been obtained using combination of superresolution microscopy, single molecule imaging, and electrophysiological recordings.

Steady-State Free Ca in Astrocytes Is Decreased by Experience and Impacts Arteriole Tone.

Astrocytes can control basal synaptic strength and arteriole tone via their resting Ca activity. However, whether resting astrocyte Ca can adjust to a new steady-state level, with an impact on surrounding brain cells, remains unknown. Using two-photon Ca imaging in male rat acute brain slices of the somatosensory neocortex, we found that theta burst neural activity produced an unexpected long-lasting reduction in astrocyte free Ca in the soma and endfeet.

Astroglial glutamate transporters in the brain: Regulating neurotransmitter homeostasis and synaptic transmission.

Astrocytes, the major glial cell type in the central nervous system (CNS), are critical for brain function and have been implicated in various disorders of the central nervous system. These cells are involved in a wide range of cerebral processes including brain metabolism, control of central blood flow, ionic homeostasis, fine-tuning synaptic transmission, and neurotransmitter clearance. Such varied roles can be efficiently carried out due to the intimate interactions astrocytes maintain with neurons, the vasculature, as well as with other glial cells.

Surface diffusion of astrocytic glutamate transporters shapes synaptic transmission.

Control of the glutamate time course in the synapse is crucial for excitatory transmission. This process is mainly ensured by astrocytic transporters, high expression of which is essential to compensate for their slow transport cycle. Although molecular mechanisms regulating transporter intracellular trafficking have been identified, the relationship between surface transporter dynamics and synaptic function remains unexplored.

Interleukin-1alpha and HMGB1 mediate hippocampal dysfunction in SIGIRR-deficient mice.

Single-Ig-interleukin-1 related receptor (SIGIRR) is a member of the interleukin (IL)-1/Toll-like receptor (TLR) family. It negatively regulates inflammation, rendering SIGIRR(-/-) mice more susceptible to inflammatory challenge. This susceptibility extends to the brain, where increased responsiveness to lipopolysaccharide has been observed in SIGIRR-deficient mice.