title: Disinhibitory Action of Astrocytic GABA at the Perforant Path to Dentate Gyrus Granule Neuron Synapse Reverses to Inhibitory in Alzheimer's Disease Model.
abstract: Like neurons, astrocytes produce and release GABA to influence neuronal signaling. At the perforant path to dentate gyrus granule neuron synapse, GABA from astrocyte was found to be a strong inhibitory factor, which impairs synaptic transmission, synaptic plasticity and memory in Alzheimer's disease. Although astrocytic GABA is observed in many brain regions, its physiological role has not been clearly demonstrated yet. Here, we show that astrocytic GABA exerts disinhibitory action to dentate granule neurons by targeting GABAB receptors of GABAergic interneurons in wild-type mice. This disinhibitory effect is specific to a low intensity of electrical stimulation at perforant path fibers. Inversely in Alzheimer's disease model mice, astrocytic GABA targets GABAA receptors and exerts inhibitory action by reducing release probability of glutamatergic perforant path terminals. These results suggest that astrocytic GABA differentially modulates the signaling from cortical input to dentate gyrus under physiological and pathological conditions.
authors.affiliation: Center for Neuroscience and Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
authors.forename: Oleg
authors.initials: O
authors.lastname: Yarishkin
authors.affiliation: Center for Neuroscience and Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
authors.forename: Jaekwang
authors.initials: J
authors.lastname: Lee
authors.affiliation: Center for Neuroscience and Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea. ; Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.
authors.forename: Seonmi
authors.initials: S
authors.lastname: Jo
authors.affiliation: Center for Neuroscience and Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea. ; Neuroscience Program, University of Science and Technology (UST), Daejeon 34113, Korea.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Hwang
authors.affiliation: Center for Neuroscience and Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea. ; Neuroscience Program, University of Science and Technology (UST), Daejeon 34113, Korea. ; KU-KIST Graduate School of Converging Science and Technology, Seoul 02841, Korea.
authors.forename: C Justin
authors.initials: CJ
authors.lastname: Lee
keywords: Alzheimer's disease; Astrocyte; Dentate gyrus; GABA; Perforant path