Multi‐array silicon probes with integrated optical fibers: light‐assisted perturbation and recording of local neural circuits in the behaving animal

Recordings of large neuronal ensembles and neural stimulation of high spatial and temporal precision are important requisites for studying the real‐time dynamics of neural networks. Multiple‐shank silicon probes enable large‐scale monitoring of individual neurons. Optical stimulation of genetically targeted neurons expressing light‐sensitive channels or other fast (milliseconds) actuators offers the means for controlled perturbation of local circuits. Here we describe a method to equip the shanks of silicon probes with micron‐scale light guides for allowing the simultaneous use of the two approaches. We then show illustrative examples of how these compact hybrid electrodes can be used in probing local circuits in behaving rats and mice. A key advantage of these devices is the enhanced spatial precision of stimulation that is achieved by delivering light close to the recording sites of the probe. When paired with the expression of light‐sensitive actuators within genetically specified neuronal populations, these devices allow the relatively straightforward and interpretable manipulation of network activity.

[1]  D. Amaral,et al.  The three-dimensional organization of the hippocampal formation: A review of anatomical data , 1989, Neuroscience.

[2]  William T. Newsome,et al.  Cortical microstimulation influences perceptual judgements of motion direction , 1990, Nature.

[3]  K D Wise,et al.  Microfabrication techniques for integrated sensors and microsystems. , 1991, Science.

[4]  G. Buzsáki,et al.  High-frequency network oscillation in the hippocampus. , 1992, Science.

[5]  B L McNaughton,et al.  Dynamics of the hippocampal ensemble code for space. , 1993, Science.

[6]  R. Samulski Adeno-associated Viral Vectors , 1995 .

[7]  G. Buzsáki,et al.  Interneurons of the hippocampus , 1998, Hippocampus.

[8]  R. Morris Foundations of cellular neurophysiology , 1996 .

[9]  J. Csicsvari,et al.  Reliability and State Dependence of Pyramidal Cell–Interneuron Synapses in the Hippocampus an Ensemble Approach in the Behaving Rat , 1998, Neuron.

[10]  J. Csicsvari,et al.  Accuracy of tetrode spike separation as determined by simultaneous intracellular and extracellular measurements. , 2000, Journal of neurophysiology.

[11]  E. Seidemann,et al.  Dynamics of Depolarization and Hyperpolarization in the Frontal Cortex and Saccade Goal , 2002, Science.

[12]  C. Schwarz,et al.  Spatiotemporal effects of microstimulation in rat neocortex: a parametric study using multielectrode recordings. , 2003, Journal of neurophysiology.

[13]  P. Somogyi,et al.  Brain-state- and cell-type-specific firing of hippocampal interneurons in vivo , 2003, Nature.

[14]  J. Csicsvari,et al.  Massively parallel recording of unit and local field potentials with silicon-based electrodes. , 2003, Journal of neurophysiology.

[15]  E. Lehtonen,et al.  Adeno-associated viral vectors. , 2003, International review of neurobiology.

[16]  E. Bamberg,et al.  Channelrhodopsin-2, a directly light-gated cation-selective membrane channel , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[17]  J. Csicsvari,et al.  Organization of cell assemblies in the hippocampus , 2003, Nature.

[18]  W. Newsome,et al.  What electrical microstimulation has revealed about the neural basis of cognition , 2004, Current Opinion in Neurobiology.

[19]  G. Buzsáki Large-scale recording of neuronal ensembles , 2004, Nature Neuroscience.

[20]  H. Markram,et al.  Interneurons of the neocortical inhibitory system , 2004, Nature Reviews Neuroscience.

[21]  G. Buzsáki,et al.  Characterization of neocortical principal cells and interneurons by network interactions and extracellular features. , 2004, Journal of neurophysiology.

[22]  K. Deisseroth,et al.  Millisecond-timescale, genetically targeted optical control of neural activity , 2005, Nature Neuroscience.

[23]  Kensall D. Wise,et al.  Band-tunable and multiplexed integrated circuits for simultaneous recording and stimulation with microelectrode arrays , 2005, IEEE Transactions on Biomedical Engineering.

[24]  S. Arber,et al.  A Developmental Switch in the Response of DRG Neurons to ETS Transcription Factor Signaling , 2005, PLoS biology.

[25]  H. Chiel,et al.  Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[26]  T. Ishizuka,et al.  Kinetic evaluation of photosensitivity in genetically engineered neurons expressing green algae light-gated channels , 2006, Neuroscience Research.

[27]  G. Feng,et al.  Next-Generation Optical Technologies for Illuminating Genetically Targeted Brain Circuits , 2006, The Journal of Neuroscience.

[28]  J. Grieger,et al.  Production and characterization of adeno-associated viral vectors , 2006, Nature Protocols.

[29]  H. Monyer,et al.  Effects of electrically coupled inhibitory networks on local neuronal responses to intracortical microstimulation. , 2006, Journal of neurophysiology.

[30]  K. Svoboda,et al.  Channelrhodopsin-2–assisted circuit mapping of long-range callosal projections , 2007, Nature Neuroscience.

[31]  K. Deisseroth,et al.  Circuit-breakers: optical technologies for probing neural signals and systems , 2007, Nature Reviews Neuroscience.

[32]  E. Boyden,et al.  Multiple-Color Optical Activation, Silencing, and Desynchronization of Neural Activity, with Single-Spike Temporal Resolution , 2007, PloS one.

[33]  Feng Zhang,et al.  Multimodal fast optical interrogation of neural circuitry , 2007, Nature.

[34]  G. Buzsáki,et al.  Behavior-dependent short-term assembly dynamics in the medial prefrontal cortex , 2008, Nature Neuroscience.

[35]  Matthew A Wilson,et al.  Large-scale chronically implantable precision motorized microdrive array for freely behaving animals. , 2008, Journal of neurophysiology.

[36]  P. Somogyi,et al.  Neuronal Diversity and Temporal Dynamics: The Unity of Hippocampal Circuit Operations , 2008, Science.

[37]  I. Fried,et al.  Internally Generated Reactivation of Single Neurons in Human Hippocampus During Free Recall , 2008, Science.

[38]  Daryl R Kipke,et al.  Advanced Neurotechnologies for Chronic Neural Interfaces: New Horizons and Clinical Opportunities , 2008, The Journal of Neuroscience.

[39]  S. Sternson,et al.  A FLEX Switch Targets Channelrhodopsin-2 to Multiple Cell Types for Imaging and Long-Range Circuit Mapping , 2008, The Journal of Neuroscience.

[40]  Asohan Amarasingham,et al.  Internally Generated Cell Assembly Sequences in the Rat Hippocampus , 2008, Science.

[41]  Jessica A. Cardin,et al.  Driving fast-spiking cells induces gamma rhythm and controls sensory responses , 2009, Nature.

[42]  K. Svoboda,et al.  Reverse engineering the mouse brain , 2009, Nature.

[43]  K. Svoboda,et al.  The subcellular organization of neocortical excitatory connections , 2009, Nature.

[44]  R. Reid,et al.  Direct Activation of Sparse, Distributed Populations of Cortical Neurons by Electrical Microstimulation , 2009, Neuron.

[45]  Jacob G. Bernstein,et al.  Millisecond-Timescale Optical Control of Neural Dynamics in the Nonhuman Primate Brain , 2009, Neuron.

[46]  Jeroen J Bos,et al.  The Lantern: An ultra-light micro-drive for multi-tetrode recordings in mice and other small animals , 2009, Journal of Neuroscience Methods.

[47]  K. Deisseroth,et al.  Parvalbumin neurons and gamma rhythms enhance cortical circuit performance , 2009, Nature.

[48]  Patrick D Wolf,et al.  A fully implantable 96-channel neural data acquisition system , 2009, Journal of neural engineering.

[49]  G. Buzsáki,et al.  Distinct Representations and Theta Dynamics in Dorsal and Ventral Hippocampus , 2010, The Journal of Neuroscience.

[50]  Asohan Amarasingham,et al.  Hippocampus Internally Generated Cell Assembly Sequences in the Rat , 2011 .