Plasticity of astroglial networks in olfactory glomeruli

Abstract

Several recent findings have shown that neurons as well as astrocytes are organized into networks. Indeed, astrocytes are interconnected through connexin-formed gap junction channels allowing exchanges of ions and signaling molecules. The aim of this study is to characterize astrocyte network properties in mouse olfactory glomeruli where neuronal connectivity is highly ordered. Dyecoupling experiments performed in olfactory bulb acute slices (P16-P22) highlight a preferential communication between astrocytes within glomeruli and not between astrocytes in adjacent glomeruli. Such organization relies on the oriented morphology of glomerular astrocytes to the glomerulus center and the enriched expression of two astroglial connexins (Cx43 and Cx30) within the glomeruli. Glomerular astrocytes detect neuronal activity showing membrane potential fluctuations correlated with glomerular local field potentials. Accordingly, gap junctional coupling of glomerular networks is reduced when neuronal activity is silenced by TTX treatment or after early sensory deprivation. Such modulation is lost in Cx30 but not in Cx43 KO mice, indicating that Cx30-formed channels are the molecular targets of this activity-dependent modulation. Extracellular potassium is a key player in this neuroglial interaction, because (i) the inhibition of dye coupling observed in the presence of TTX or after sensory deprivation is restored by increasing [K + ] e and (ii) treatment with a K ir channel blocker inhibits dye spread between glomerular astrocytes. Together, these results demonstrate that extracellular potassium generated by neuronal activity modulates Cx30-mediated gap junctional communication between glomerular astrocytes, indicating that strong neuroglial interactions take place at this first relay of olfactory information processing.O lfactory glomeruli (OG) represent functional units where olfactory signals are first processed (1, 2). The combination of the anatomical organization and the functional activity results in a highly ordered spatial map of glomerular activation associated with each odor (3, 4). However, this well-described organization refers only to neuronal circuits, and information concerning astroglial connectivity is lacking. In the brain, astrocytes express the highest rate of connexins (Cxs), the protein constituents of gap junction channels that provide the molecular basis for direct cellto-cell communication. Though astrocytes were initially thought to form a glial syncitium, there is now evidence for a more specialized network organization (5). As increasing evidence argues for dynamic interactions between neurons and astrocytes (6), a coordinated population of astrocytes working in concert with neurons could contribute to sensory integration occurring in OG. The goal of this study is to determine how Cx-mediated intercellular communication in astrocytes is organized and modulated in this brain structure characterized by functional units. Features of OG astrocytes studied so far include their morphology (7,8), membrane...

Astrocytic glutamate transport regulates a Drosophila CNS synapse that lacks astrocyte ensheathment

“…The restriction of astrocyte coupling to cells within a hemisegment is reminiscent of findings in the olfactory bulb (Roux et al, 2011) and barrel cortex (Houades et al, 2008), where astrocytes were preferentially coupled within, and not across, anatomo-functional compartments (also reviewed in Giaume and Liu, 2012). We found no difference in the frequency of coupling in channelrhodopsin-stimulated and unstimulated preparations.…”

“…We hypothesized that the subset of astrocytes that were filled with dye during experiments in which neuronal activity was artificially increased (via channelrhodopsin expression under the control of the D42-GAL4 driver, see "Astrocyte response to broad neuronal network activity" below) would display a higher frequency of astrocyte dye-coupling (Roux et al, 2011). However, there was no difference between our sample of unstimulated preparations, where 4 of 14 astrocytes were dye-coupled, and stimulated preparations, where 4 of 12 astrocytes were dye-coupled.…”

Astroglial connexin 43 sustains glutamatergic synaptic efficacy

“…Cx functions, however, extend beyond GJ communication, and also include extracellular exchanges mediated by hemichannels, as well as channel-independent functions involving cell adhesion or signalling [4,13]. Interestingly, Cx43 differs from Cx30 in several aspects, including temporal and regional distribution patterns [4], biophysical properties, intracellular C-terminal domain [14], regulation by neuronal activity [15] and contribution to behaviour [7,16,17]. Therefore, determining whether each Cx confers specific features to astrocytes, and unravelling the underlying differential regulations of neurotransmission are crucial issues.…”

Topology Drives Calcium Wave Propagation in 3D Astrocyte Networks

“…Beyond this general setting, the structure of astrocyte networks is still unknown. Recent experimental evidence however suggests that astrocytes networks display different topologies depending on the brain region [18] and even that neuronal activity can modify these topologies by regulating inter-astrocyte GJC [9]. In contrast, in the modeling literature, most articles consider astrocyte networks embedded in a two dimensional space [7,13] and connected using regular lattices [10,11,13].…”