title: Optogenetic stimulation reveals distinct modulatory properties of thalamostriatal vs corticostriatal glutamatergic inputs to fast-spiking interneurons.
abstract: Parvalbumin-containing fast-spiking interneurons (FSIs) exert a powerful feed-forward GABAergic inhibition on striatal medium spiny neurons (MSNs), playing a critical role in timing striatal output. However, how glutamatergic inputs modulate their firing activity is still unexplored. Here, by means of a combined optogenetic and electrophysiological approach, we provide evidence for a differential modulation of cortico- vs thalamo-striatal synaptic inputs to FSIs in transgenic mice carrying light-gated ion channels channelrhodopsin-2 (ChR2) in glutamatergic fibers. Corticostriatal synapses show a postsynaptic facilitation, whereas thalamostriatal synapses present a postsynaptic depression. Moreover, thalamostriatal synapses exhibit more prominent AMPA-mediated currents than corticostriatal synapses, and an increased release probability. Furthermore, during current-evoked firing activity, simultaneous corticostriatal stimulation increases bursting activity. Conversely, thalamostriatal fiber activation shifts the canonical burst-pause activity to a more prolonged, regular firing pattern. However, this change in firing pattern was accompanied by a significant rise in the frequency of membrane potential oscillations. Notably, the responses to thalamic stimulation were fully abolished by blocking metabotropic glutamate 1 (mGlu1) receptor subtype, whereas both acetylcholine and dopamine receptor antagonists were ineffective. Our findings demonstrate that cortical and thalamic glutamatergic input differently modulate FSIs firing activity through specific intrinsic and synaptic properties, exerting a powerful influence on striatal outputs.
authors.affiliation: University of Rome "Tor Vergata", Dept. of Systems Medicine, via Montpellier 1 -00133, Rome.|Fondazione Santa Lucia IRCCS, Neurophysiology and Plasticity lab, via Fosso di Fiorano 64 -00143, Rome.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sciamanna
authors.affiliation: Fondazione Santa Lucia IRCCS, Neurophysiology and Plasticity lab, via Fosso di Fiorano 64 -00143, Rome.
authors.forename: Giulia
authors.initials: G
authors.lastname: Ponterio
authors.affiliation: Fondazione Santa Lucia IRCCS, Neurophysiology and Plasticity lab, via Fosso di Fiorano 64 -00143, Rome.
authors.forename: Georgia
authors.initials: G
authors.lastname: Mandolesi
authors.affiliation: Fondazione Santa Lucia IRCCS, Neurophysiology and Plasticity lab, via Fosso di Fiorano 64 -00143, Rome.
authors.forename: Paola
authors.initials: P
authors.lastname: Bonsi
authors.affiliation: University of Rome "Tor Vergata", Dept. of Systems Medicine, via Montpellier 1 -00133, Rome.|Fondazione Santa Lucia IRCCS, Neurophysiology and Plasticity lab, via Fosso di Fiorano 64 -00143, Rome.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pisani
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D000075402:Channelrhodopsins; D003342:Corpus Striatum / Q000502:physiology*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D016202:N-Methylaspartate / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D013569:Synapses / Q000378:metabolism; D013788:Thalamus / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
chemical_list: D000075402:Channelrhodopsins; D011993:Recombinant Fusion Proteins; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D002118:Calcium