Lamina‐specific properties of spinal astrocytes

Abstract

Astrocytes are indispensable for proper neuronal functioning. Given the diverse needs of neuronal circuits and the variety of tasks astrocytes perform, the perceived homogeneous nature of astrocytes has been questioned. In the spinal dorsal horn, complex neuronal circuitries regulate the integration of sensory information of different modalities. The dorsal horn is organized in a distinct laminar manner based on termination patterns of high‐ and low‐threshold afferent fibers and neuronal properties. Neurons in laminae I (L1) and II (L2) integrate potentially painful, nociceptive information, whereas neurons in lamina III (L3) and deeper laminae integrate innocuous, tactile information from the periphery. Sensory information is also integrated by an uncharacterized network of astrocytes. How these lamina‐specific characteristics of neuronal circuits of the dorsal horn are of functional importance for properties of astrocytes is currently unknown. We addressed if astrocytes in L1, L2, and L3 of the upper dorsal horn of mice are differentially equipped for the needs of neuronal circuits that process sensory information of different modalities. We found that astrocytes in L1 and L2 were characterized by a higher density, higher expression of GFAP, Cx43, and GLAST and a faster coupling speed than astrocytes located in L3. L1 astrocytes were more responsive to Kir4.1 blockade and had higher levels of AQP4 compared to L3 astrocytes. In contrast, basic membrane properties, network formation, and somatic intracellular calcium signaling were similar in L1–L3 astrocytes. Our data indicate that the properties of spinal astrocytes are fine‐tuned for the integration of nociceptive versus tactile information.

A perspective on astrocyte regulation of neural circuit function and animal behavior

“…• Transporter expression (e.g., GLAST) • Ion channel expression (e.g., Kir4.1) • Gap junctional coupling (e.g., Cx43) • Ca 2+ signaling (e.g., hippocampus vs. striatum) • Metabolism • Structural properties (e.g., GFAP expression, spine coverage) Chai et al, 2017;Fernández-Moncada et al, 2021;Herde et al, 2020;Hirrlinger et al, 2008;Kelley et al, 2018;Köhler et al, 2021;Köhler et al, 2018;Kronschläger et al, 2021;Miller et al, 2019;Oheim et al, 2018;Olsen et al, 2007 used to study primate-specific interlaminar astrocytes in mice (Padmashri et al, 2021). Strikingly, grafting human astrocytes into the mouse forebrain enhanced synaptic plasticity and learning (Han et al, 2013).…”

“…Chai et al, 2017; Fernández‐Moncada et al, 2021; Herde et al, 2020; Hirrlinger et al, 2008; Kelley et al, 2018; Köhler et al, 2021; Köhler et al, 2018; Kronschläger et al, 2021; Miller et al, 2019; Oheim et al, 2018; Olsen et al, 2007; Theis & Giaume, 2012…”

“…Recent studies have also indicated that spinal cord astrocytes are regionally heterogeneous ( Kronschläger et al, 2021 ; Molofsky et al, 2014 ; Shekhtmeyster, Carey, et al, 2021 ), that this heterogeneity is functionally relevant ( Kelley et al, 2018 ; Kohro et al., 2020 ) and associated with distinct spatiotemporal excitation patterns. For example, using translaminar imaging in behaving mice with chronically implanted microprisms, astrocytes in sensory and premotor areas of the spinal dorsal horn were found to respond to noxious mechanical stimuli and locomotion in a lamina-specific manner ( Shekhtmeyster, Carey, et al, 2021 ).…”

Lunatic Fringe-GFP Marks Lamina-Specific Astrocytes That Regulate Sensory Processing

“…In addition to distinct interactions with neurons, spinal cord astrocytes also exhibit unique physiological properties. A recent study demonstrated that while astrocytes in lamina I have faster coupling speed, higher responsiveness to potassium channel blockage and higher expression of AQP4 than astrocytes in lamina III, their basal membrane properties are similar (Kronschläger et al, 2021). This prompted us to compare passive conductance, I-V curve, and resting membrane potential between Lfng-GFP 1 and ventral Lfng-GFPastrocytes, where we found no differences between these populations.…”

“…Synaptic inputs from peripheral sensory neurons into the CNS occur in the dorsal horn of the spinal cord, which is densely populated by astrocytes. Recent studies found that dorsal astrocytes exhibit unique patterns of marker gene expression and laminar-specific coupling speed (Kronschläger et al, 2021). Accordingly, astrocytes have been implicated in sensory processing, where the inhibition of astrocyte proliferation reduced injury-induced tactile allodynia (Tsuda et al, 2011).…”