ABSTRACT:Communication between neurons rests on their capacity to change their firing pattern to encode different messages. For several vital functions, such as respiration and mastication, neurons need to generate a rhythmic firing pattern. Here we show in the rat trigeminal sensori-motor circuit for mastication that this ability depends on regulation of the extracellular Ca 2+ concentration ([Ca 2+ ] e ) by astrocytes. In this circuit, astrocytes respond to sensory stimuli that induce neuronal rhythmic activity, and their blockade with a Ca 2+ chelator prevents neurons from generating a rhythmic bursting pattern.This ability is restored by adding S100β, an astrocytic Ca 2+ -binding protein, to the extracellular space, while application of an anti-S100β antibody prevents generation of rhythmic activity. These results indicate that astrocytes regulate a fundamental neuronal property: the capacity to change firing pattern. These findings may have broad implications for many other neural networks whose functions depend on the generation of rhythmic activity.
Dendritic defects occur in neurodegenerative diseases accompanied by axonopathy,
yet the mechanisms that regulate these pathologic changes are poorly understood.
Using Thy1-YFPH mice subjected to optic nerve axotomy, we demonstrate early
retraction of retinal ganglion cell (RGC) dendrites and selective loss of
mammalian target of rapamycin (mTOR) activity, which precede soma loss. Axonal
injury triggered rapid upregulation of the stress-induced protein REDD2
(regulated in development and DNA damage response 2), a potent inhibitor of
mTOR. Short interfering RNA-mediated REDD2 knockdown restored mTOR activity and
rescued dendritic length, area and branch complexity in a rapamycin-dependent
manner. Whole-cell recordings demonstrated that REDD2 depletion leading to mTOR
activation in RGCs restored their light response properties. Lastly, we show
that REDD2-dependent mTOR activity extended RGC survival following axonal
damage. These results indicate that injury-induced stress leads to REDD2
upregulation, mTOR inhibition and dendrite pathology causing neuronal
dysfunction and subsequent cell death.
Proper function of all excitable cells depends on ion homeostasis. Nowhere is this more critical than in the brain where the extracellular concentration of some ions determines neurons' firing pattern and ability to encode information. Several neuronal functions depend on the ability of neurons to change their firing pattern to a rhythmic bursting pattern, whereas, in some circuits, rhythmic firing is, on the contrary, associated to pathologies like epilepsy or Parkinson's disease. In this review, we focus on the four main ions known to fluctuate during rhythmic firing: calcium, potassium, sodium, and chloride. We discuss the synergistic interactions between these elements to promote an oscillatory activity. We also review evidence supporting an important role for astrocytes in the homeostasis of each of these ions and describe mechanisms by which astrocytes may regulate neuronal firing by altering their extracellular concentrations. A particular emphasis is put on the mechanisms underlying rhythmogenesis in the circuit forming the central pattern generator (CPG) for mastication and other CPG systems. Finally, we discuss how an impairment in the ability of glial cells to maintain such homeostasis may result in pathologies like epilepsy and Parkinson's disease.
Light regulates physiology, mood, and behavior through signals sent to the brain by intrinsically photosensitive retinal ganglion cells (ipRGCs). How primate ipRGCs sense light is unclear, as they are rare and challenging to target for electrophysiological recording. We developed a method of acute identification within the live, ex vivo retina. Using it, we found that ipRGCs of the macaque monkey are highly specialized to encode irradiance (the overall intensity of illumination) by blurring spatial, temporal, and chromatic features of the visual scene. We describe mechanisms at the molecular, cellular, and population scales that support irradiance encoding across orders-of-magnitude changes in light intensity. These mechanisms are conserved quantitatively across the ~70 million years of evolution that separate macaques from mice.
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