title: Investigating local and long-range neuronal network dynamics by simultaneous optogenetics, reverse microdialysis and silicon probe recordings in vivo.
abstract: BACKGROUND
  The advent of optogenetics has given neuroscientists the opportunity to excite or inhibit neuronal population activity with high temporal resolution and cellular selectivity. Thus, when combined with recordings of neuronal ensemble activity in freely moving animals optogenetics can provide an unprecedented snapshot of the contribution of neuronal assemblies to (patho)physiological conditions in vivo. Still, the combination of optogenetic and silicone probe (or tetrode) recordings does not allow investigation of the role played by voltage- and transmitter-gated channels of the opsin-transfected neurons and/or other adjacent neurons in controlling neuronal activity.
  
  
  RESULTS
  We demonstrate that optogenetics and silicone probe recordings can be combined with intracerebral reverse microdialysis for the long-term delivery of neuroactive drugs around the optic fiber and silicone probe. In particular, we show the effect of antagonists of T-type Ca(2+) channels, hyperpolarization-activated cyclic nucleotide-gated channels and metabotropic glutamate receptors on silicone probe-recorded activity of the local opsin-transfected neurons in the ventrobasal thalamus, and demonstrate the changes that the block of these thalamic channels/receptors brings about in the network dynamics of distant somatotopic cortical neuronal ensembles.
  
  
  METHODS
  This is the first demonstration of successfully combining optogenetics and neuronal ensemble recordings with reverse microdialysis. This combination of techniques overcomes some of the disadvantages that are associated with the use of intracerebral injection of a drug-containing solution at the site of laser activation.
  
  
  CONCLUSIONS
  The combination of reverse microdialysis, silicone probe recordings and optogenetics can unravel the short and long-term effects of specific transmitter- and voltage-gated channels on laser-modulated firing at the site of optogenetic stimulation and the actions that these manipulations exert on distant neuronal populations.
authors.affiliation: Neuroscience Division, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK.
authors.forename: Hannah
authors.initials: H
authors.lastname: Taylor
authors.affiliation: Neuroscience Division, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK.
authors.forename: Joscha T
authors.initials: JT
authors.lastname: Schmiedt
authors.affiliation: Neuroscience Division, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK; Department of Pharmacology, Faculty of Pharmacy, Instanbul University, Istanbul, Turkey.
authors.forename: Nihan
authors.initials: N
authors.lastname: Carçak
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Marmara University, Istanbul, Turkey.
authors.forename: Filiz
authors.initials: F
authors.lastname: Onat
authors.affiliation: Neuroscience Division, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK; Department of Biochemistry and Physiology, University of Malta, Malta.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Giovanni
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UM CR18, Neuroscience Paris Seine (NPS), Paris F-75005, France; CNRS, UMR 8246, NPS, Paris F-75005, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Lambert
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UM CR18, Neuroscience Paris Seine (NPS), Paris F-75005, France; CNRS, UMR 8246, NPS, Paris F-75005, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Leresche
authors.affiliation: Neuroscience Division, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK. Electronic address: crunelli@cardiff.ac.uk.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Crunelli
authors.affiliation: Neuroscience Division, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, UK. Electronic address: davidfo@cardiff.ac.uk.
authors.forename: Francois
authors.initials: F
authors.lastname: David
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000378:metabolism; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000378:metabolism; D003700:Delta Rhythm / Q000187:drug effects / Q000502:physiology; D055615:Electrical Equipment and Supplies; D004569:Electroencephalography / Q000295:instrumentation / Q000379:methods; D004576:Electromyography; D008297:Male; D017551:Microdialysis / Q000295:instrumentation / Q000379:methods*; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology / Q000601:surgery; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D019635:Neurosurgical Procedures; D062308:Optogenetics / Q000295:instrumentation / Q000379:methods*; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D012815:Signal Processing, Computer-Assisted; D012828:Silicones; D013788:Thalamus / Q000187:drug effects / Q000502:physiology* / Q000601:surgery
chemical_list: D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D054815:Cyclic Nucleotide-Gated Cation Channels; D018094:Receptors, Metabotropic Glutamate; D012828:Silicones
keywords: Cortex; Delta waves; EEG; HCN channels; Metabotropic glutamate receptors; Sleep spindles; Slow waves; T-type Ca(2+) channels; Thalamus