Interneuron-specific signaling evokes distinctive somatostatin-mediated responses in adult cortical astrocytes

Abstract

The signaling diversity of GABAergic interneurons to post-synaptic neurons is crucial to generate the functional heterogeneity that characterizes brain circuits. Whether this diversity applies to other brain cells, such as the glial cells astrocytes, remains unexplored. Using optogenetics and two-photon functional imaging in the adult mouse neocortex, we here reveal that parvalbumin- and somatostatin-expressing interneurons, two key interneuron classes in the brain, differentially signal to astrocytes inducing weak and robust GABAB receptor-mediated Ca2+ elevations, respectively. Furthermore, the astrocyte response depresses upon parvalbumin interneuron repetitive stimulations and potentiates upon somatostatin interneuron repetitive stimulations, revealing a distinguished astrocyte plasticity. Remarkably, the potentiated response crucially depends on the neuropeptide somatostatin, released by somatostatin interneurons, which activates somatostatin receptors at astrocytic processes. Our study unveils, in the living brain, a hitherto unidentified signaling specificity between interneuron subtypes and astrocytes opening a new perspective into the role of astrocytes as non-neuronal components of inhibitory circuits.

Gi/o protein‐coupled receptors inhibit neurons but activate astrocytes and stimulate gliotransmission

“…Astrocytes are emerging as important cells in brain function by exchanging signaling with neurons through their participation in the tripartite synapse (Araque, Parpura, Sanzgiri, & Haydon, ). Rather than exhibiting electrical excitability like neurons, astrocytes display a form of excitability based on changes in intracellular Ca 2+ concentration (Araque et al, ; Araque, Carmignoto, & Haydon, ; Di Castro et al, ; Haydon & Carmignoto, ; Mariotti et al, ; Navarrete & Araque, ; Panatier et al, ; Perea et al, ; Perea & Araque, ; Perea, Navarrete, & Araque, ; Verkhratsky & Kettenmann, ; Volterra, Liaudet, & Savtchouk, ; Volterra & Meldolesi, ). Upon activation, astrocytes can release their own signaling molecules, termed gliotransmitters, that regulate neuronal excitability, synaptic transmission, and plasticity (Araque et al, ; Bezzi et al, ; Halassa & Haydon, ; Rusakov, ; Volterra & Meldolesi, ) see however (Fiacco & McCarthy, ).…”

GLIA Porto 2019: Abstracts Oral Presentations, Posters, Indexes

“…The blood is recruited to the capillary bed from the brain surface via penetrating arteries and arterioles. Recently, we provided in vivo evidence of an interneuron type-specific signalling to astrocytes in the mouse somatosensory cortex (Mariotti et al 2018). Since enhanced blood flow is generated by neuronal activation in deeper layers of the brain, the basis of vessel dilation differs between the cortical layers.…”

Whole cell patch clamp analysis of non-synaptic and synaptic signaling in rodent and human supragranular neocortex

“…In contrast, previous studies showing astrocytic calcium signalling due to GABA B receptor activation (Covelo and Araque, 2018;Kang et al, 1998;Mariotti et al, 2018;Meier, Kafitz, and Rose, 2008) or gliotransmission (Fiacco and McCarthy, 2018;Sloan and Barres, 2014), were shown mainly in cell cultures or in slice preparations from young rodents (p12-p25), in the timeframe where synaptogenesis takes place (Freeman, 2010). Interestingly, even the most recent articles supporting GABA B receptor presence and signalling in astrocytes of the adult cortex utilize young rodents for their key experiments (Covelo and Araque, 2018;Mariotti et al, 2018), probably due to technical limitations. We hypothesize that astrocytes are involved in GABA B receptor dependent calcium signaling only in young rodents before astrocytes gain their mature functions.…”

“…In spite of the apparent absence of synapses on other glial cells, the presence of GABA receptors and transporters is well established (Eulenburg and Gomeza, 2010;Porter and McCarthy, 1997), and depolarizing GABAergic responses are characteristic of glia (Kettenmann, Backus, and Schachner, 1984). Accordingly, potentially non-synaptic GABAergic interactions between neurons and glia have been suggested by exogenously applied agonists (Kettenmann, Backus, and Schachner, 1984;Meier, Kafitz, and Rose, 2008) or prolonged, high-frequency stimulation of GABAergic interneurons (Covelo and Araque, 2018;Egawa et al, 2013;Kaila et al, 1997;Kang et al, 1998;Mariotti et al, 2018;Perea et al, 2016). However, evidence for GABA-evoked astrocyte activation by physiological activity processes is lacking.…”

“…Our experiments were performed in brain slices prepared from young adult rats (p25-46, p37.4 ± 4.5) where the electrophysiological, anatomical and molecular properties of astrocytes are considered mature (Bushong, Martone, and Ellisman, 2004;Bushong et al, 2002;Cahoy et al, 2008;Freeman, 2010;Meier, Kafitz, and Rose, 2008;Mishima and Hirase, 2010;Ogata and Kosaka, 2002;Sun et al, 2013;Zhou, 2005). In contrast, previous studies showing astrocytic calcium signalling due to GABA B receptor activation (Covelo and Araque, 2018;Kang et al, 1998;Mariotti et al, 2018;Meier, Kafitz, and Rose, 2008) or gliotransmission (Fiacco and McCarthy, 2018;Sloan and Barres, 2014), were shown mainly in cell cultures or in slice preparations from young rodents (p12-p25), in the timeframe where synaptogenesis takes place (Freeman, 2010). Interestingly, even the most recent articles supporting GABA B receptor presence and signalling in astrocytes of the adult cortex utilize young rodents for their key experiments (Covelo and Araque, 2018;Mariotti et al, 2018), probably due to technical limitations.…”