Reciprocal interaction between GABAergic interneurons and astrocytes: implications for epileptiform activities

In a cortical slice model of focal seizures we recently reported that: i- astrocytes may favor ictal discharge generation (Gomez-Gonzalo et al 2010) and ii- ictal discharge propagation is controlled by parvalbumin fastspiking (Pv-FS) interneurons (Cammarota et al. 2013). We here advance the hypothesis of a reciprocal signaling between Pv-FS interneurons and astrocytes that contribute to control neuronal network excitability and epileptiform activities. Slices containing epileptogenic regions like entorhinal cortex and temporal cortex (EC, TC) or other regions like somatosensory cortex (SSC) were loaded with Fluo-4AM (or OGB1-AM) and SR101. We found that a large group of astrocytes (~60 %) are similarly activated by GABA or the GABAB agonist baclofen, showing large somatic Ca2+ increases. In optogenetic experiments we found that selective stimulation of Pv-FS interneurons with blue light evokes astrocytic Ca2+ events. Current pulse depolarization of single Pv-FS interneurons through a patch-pipette also evoked Ca2+ elevations in nearby astrocytes. Patch-clamp recordings from pyramidal neurons and Pv-FS interneurons revealed that GABAmediated astrocytic activation evoked NMDA receptor-mediated slow inward currents (SICs) in both pyramidal and Pv-FS interneurons. Notably, due to the different firing threshold in the two cell types, only 14% of GABA-evoked SICs reached action potential threshold in Pv-FS interneurons with respect to 63% of pyramidal neurons. Altogether our data show that astrocytes respond to GABAergic interneurons and release glutamate increasing neuronal network excitability. The elucidation of astrocytes-interneurons reciprocal interactions has the potential to unveil novel mechanisms for the modulation of network activity and generation/propagation of focal seizures.