scholarly journals Scaling up to meet new challenges of brain and behaviour: Deep brain electrophysiology in freely moving sheep

2021 ◽  
Author(s):  
Nikolas Perentos ◽  
Marino Krstulovic ◽  
A Jennifer Morton
Keyword(s):  
Brain Function ◽  
Large Scale ◽  
Electrophysiological Recording ◽  
Large Animal ◽  
Freely Moving ◽  
Hippocampal Theta ◽  
Exceptional Stability ◽  
Oscillatory Rhythms ◽  
Deep Brain

While rodents are arguably the easiest animals to use for studying brain function, relying on them as model species for translational research comes with its own sets of limitations. Here, we propose sheep as a practical large animal species for in vivo brain function studies performed in naturalistic settings. To demonstrate their experimental usefulness, we performed proof-of-principle deep brain electrophysiological recording experiments from unrestrained sheep. Recordings were made from cortex and hippocampus both whilst sheep performed goal-directed behaviours (two-choice discrimination tasks), and across states of vigilance that included natural sleep. Hippocampal and cortical oscillatory rhythms were consistent with those seen in rodents and non-human primates, and included cortical alpha oscillations during immobility, hippocampal theta oscillations (5-6Hz) during locomotion and hippocampal sharp wave ripple oscillations (~150 Hz) during immobility. Moreover, we found clear examples of neurons whose activity was modulated by task, speed of locomotion, spatial position, reward and vigilance states. Recordings were conducted over a period of many months. Due to the exceptional stability of individual electrodes we were able to record from some neurons continuously for more than 1 month. Together these experiments demonstrate that sheep are an excellent experimental animal model to use in longitudinal electrophysiological and imaging studies, particularly those requiring a large brained mammal, large scale recordings across distributed neuronal networks, experimentation outside the confounds of the traditional laboratory, or all the above concomitantly.

Implantable neural interfaces

2018 ◽  
Author(s):  
Stefano Vassanelli
Keyword(s):  
Brain Function ◽  
Large Scale ◽  
Ionic Channels ◽  
Patch Clamp Technique ◽  
Advantages And Disadvantages ◽  
Optogenetic Stimulation ◽  
Physical Interfaces ◽  
The Brain

Establishing direct communication with the brain through physical interfaces is a fundamental strategy to investigate brain function. Starting with the patch-clamp technique in the seventies, neuroscience has moved from detailed characterization of ionic channels to the analysis of single neurons and, more recently, microcircuits in brain neuronal networks. Development of new biohybrid probes with electrodes for recording and stimulating neurons in the living animal is a natural consequence of this trend. The recent introduction of optogenetic stimulation and advanced high-resolution large-scale electrical recording approaches demonstrates this need. Brain implants for real-time neurophysiology are also opening new avenues for neuroprosthetics to restore brain function after injury or in neurological disorders. This chapter provides an overview on existing and emergent neurophysiology technologies with particular focus on those intended to interface neuronal microcircuits in vivo. Chemical, electrical, and optogenetic-based interfaces are presented, with an analysis of advantages and disadvantages of the different technical approaches.

scholarly journals In vivo photopharmacology enabled by multifunctional fibers

2020 ◽  
Author(s):  
James A. Frank ◽  
Marc-Joseph Antonini ◽  
Po-Han Chiang ◽  
Andres Canales ◽  
David B. Konrad ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Optical Switch ◽  
Brain Regions ◽  
Behavioral Experiments ◽  
Mesolimbic Pathway ◽  
Molecular Neuroscience ◽  
Freely Moving ◽  
Thermal Drawing ◽  
Deep Brain

ABSTRACTTo reversibly manipulate neural circuits with increased spatial and temporal control, photoswitchable ligands can add an optical switch to a target receptor or signaling cascade. This approach, termed photopharmacology, has been enabling to molecular neuroscience, however, its application to behavioral experiments has been impeded by a lack of integrated hardware capable of delivering both light and compounds to deep brain regions in moving subjects. Here, we devise a hybrid photochemical genetic approach to target neurons using a photoswitchable agonist of capsaicin receptor (TRPV1), red-AzCA-4. Using the thermal drawing process we created multifunctional fibers that can deliver viruses, photoswitchable ligands, and light to deep brain regions in awake, freely moving mice. We implanted our fibers into the ventral tegmental area (VTA), a midbrain hub of the mesolimbic pathway, and used them to deliver a transgene coding for TRPV1. This sensitized excitatory VTA neurons to red-AzCA-4, and allowed us to optically control conditioned place preference using a mammalian ion-channel, thus extending applications of photopharmacology to behavioral experiments. Applied to endogenous receptors, our approach may accelerate studies of molecular mechanisms underlying animal behavior.

scholarly journals Injectable Nanoelectrodes Enable Wireless Deep Brain Stimulation of Native Tissue in Freely Moving Mice

2020 ◽  
Author(s):  
Kristen L. Kozielski ◽  
Ali Jahanshahi ◽  
Hunter B. Gilbert ◽  
Yan Yu ◽  
Önder Erin ◽  
...  
Keyword(s):  
Behavioral Changes ◽  
Less Invasive ◽  
Magnetoelectric Materials ◽  
The Central Nervous System ◽  
Freely Moving ◽  
The Brain ◽  
Deep Brain ◽  
Stimulation Of

AbstractDevices that electrically modulate the central nervous system have enabled important breakthroughs in the management of neurological and psychiatric disorders. Such devices typically have centimeter-scale dimensions, requiring surgical implantation and wired-in powering. Using smaller, remotely powered materials could lead to less invasive neuromodulation. Herein, we present injectable magnetoelectric nanoelectrodes that wirelessly transmit electrical signals to the brain in response to an external magnetic field. Importantly, this mechanism of modulation requires no genetic modification of the brain, and allows animals to freely move during stimulation. Using these nanoelectrodes, we demonstrate neuronal modulation in vitro and in deep brain targets in vivo. We also show that local thalamic modulation promotes modulation in other regions connected via basal ganglia circuitry, leading to behavioral changes in mice. Magnetoelectric materials present a versatile platform technology for less invasive, deep brain neuromodulation.

scholarly journals Wireless optoelectronic photometers for monitoring neuronal dynamics in the deep brain

2018 ◽  
Vol 115 (7) ◽  
pp. E1374-E1383 ◽  
Author(s):  
Luyao Lu ◽  
Philipp Gutruf ◽  
Li Xia ◽  
Dionnet L. Bhatti ◽  
Xinying Wang ◽  
...  
Keyword(s):  
In Vivo Studies ◽  
Polymer Support ◽  
Neuronal Dynamics ◽  
Physical Constraints ◽  
Neuroscience Research ◽  
Calcium Indicators ◽  
Freely Moving ◽  
Complex Features ◽  
Deep Brain

Capabilities for recording neural activity in behaving mammals have greatly expanded our understanding of brain function. Some of the most sophisticated approaches use light delivered by an implanted fiber-optic cable to optically excite genetically encoded calcium indicators and to record the resulting changes in fluorescence. Physical constraints induced by the cables and the bulk, size, and weight of the associated fixtures complicate studies on natural behaviors, including social interactions and movements in environments that include obstacles, housings, and other complex features. Here, we introduce a wireless, injectable fluorescence photometer that integrates a miniaturized light source and a photodetector on a flexible, needle-shaped polymer support, suitable for injection into the deep brain at sites of interest. The ultrathin geometry and compliant mechanics of these probes allow minimally invasive implantation and stable chronic operation. In vivo studies in freely moving animals demonstrate that this technology allows high-fidelity recording of calcium fluorescence in the deep brain, with measurement characteristics that match or exceed those associated with fiber photometry systems. The resulting capabilities in optical recordings of neuronal dynamics in untethered, freely moving animals have potential for widespread applications in neuroscience research.

scholarly journals Multichannel optogenetics combined with laminar recordings for ultra-controlled neuronal interrogation

2021 ◽  
Author(s):  
David Eriksson ◽  
Artur Schneider ◽  
Anupriya Thirumalai ◽  
Mansour Alyahyaey ◽  
Brice de la Crompe ◽  
...  
Keyword(s):  
Optical Fibers ◽  
Brain Function ◽  
Large Scale ◽  
High Quality ◽  
Brain Areas ◽  
New Techniques ◽  
Neuronal Communication ◽  
Flexible Fiber ◽  
Freely Moving ◽  
New Framework

Abstract Highlights: To combine large-scale recordings with optical perturbation we have developed a number of new techniques such as thin optical side-emitting fibers, a fiber matrix connector for thin fibers, an electro-optical commutator for multiple thin fibers, an active patch cord, a flexible fiber bundle ribbon cable, and a modular multi-optrode implantation holder.Summary: Simultaneous large-scale recordings and optogenetic interventions hold the promise to decipher the fast-paced and multifaceted dialogue between neurons that sustains brain function. Here we developed unprecedentedly thin, cell-sized Lambertian side-emitting optical fibers and combined them with silicon probes to achieve high quality recordings and ultrafast multichannel optogenetic inhibition in freely moving animals. Our new framework paves the way for large-scale photo tagging and controlled interrogation of rapid neuronal communication in any combination of brain areas.

scholarly journals Low and high frequency intracranial neural signals match in the human associative cortex

2022 ◽  
Author(s):  
Corentin Jacques ◽  
Jacques Jonas ◽  
Sophie Colnat-Coulbois ◽  
Louis Maillard ◽  
Bruno Rossion
Keyword(s):  
Human Brain ◽  
High Frequency ◽  
Brain Function ◽  
Large Scale ◽  
Temporal Cortex ◽  
High Signal ◽  
Associative Cortex ◽  
The Relationship ◽  
Intracranial Recordings

In vivo intracranial recordings of neural activity offer a unique opportunity to understand human brain function. Intracranial electrophysiological (iEEG) activity related to sensory, cognitive or motor events manifests mostly in two types of signals: event-related local field potentials in lower frequency bands (<30 Hz, LF) and broadband activity in the higher end of the frequency spectrum (>30 Hz, High frequency, HF). While most current studies rely exclusively on HF, thought to be more focal and closely related to spiking activity, the relationship between HF and LF signals is unclear, especially in human associative cortex. Here we provide a large-scale in-depth investigation of the spatial and functional relationship between these 2 signals based on intracranial recordings from 121 individual brains (8000 recording sites). We measure selective responses to complex ecologically salient visual stimuli – human faces - across a wide cortical territory in the ventral occipito-temporal cortex (VOTC), with a frequency-tagging method providing high signal-to-noise ratio (SNR) and the same objective quantification of signal and noise for the two frequency ranges. While LF face-selective activity has higher SNR across the VOTC, leading to a larger number of significant electrode contacts especially in the anterior temporal lobe, LF and HF display highly similar spatial, functional, and timing properties. Specifically, and contrary to a widespread assumption, our results point to nearly identical spatial distribution and local spatial extent of LF and HF activity at equal SNR. These observations go a long way towards clarifying the relationship between the two main iEEG signals and reestablish the informative value of LF iEEG to understand human brain function.

scholarly journals Nonresonant powering of injectable nanoelectrodes enables wireless deep brain stimulation in freely moving mice

2021 ◽  
Vol 7 (3) ◽  
pp. eabc4189
Author(s):  
K. L. Kozielski ◽  
A. Jahanshahi ◽  
H. B. Gilbert ◽  
Y. Yu ◽  
Ö. Erin ◽  
...  
Keyword(s):  
Neural Tissue ◽  
Behavioral Changes ◽  
Less Invasive ◽  
Magnetoelectric Materials ◽  
Freely Moving ◽  
Risk Of Hemorrhage ◽  
The Brain ◽  
Deep Brain

Devices that electrically modulate the deep brain have enabled important breakthroughs in the management of neurological and psychiatric disorders. Such devices are typically centimeter-scale, requiring surgical implantation and wired-in powering, which increases the risk of hemorrhage, infection, and damage during daily activity. Using smaller, remotely powered materials could lead to less invasive neuromodulation. Here, we present injectable, magnetoelectric nanoelectrodes that wirelessly transmit electrical signals to the brain in response to an external magnetic field. This mechanism of modulation requires no genetic modification of neural tissue, allows animals to freely move during stimulation, and uses nonresonant carrier frequencies. Using these nanoelectrodes, we demonstrate neuronal modulation in vitro and in deep brain targets in vivo. We also show that local subthalamic modulation promotes modulation in other regions connected via basal ganglia circuitry, leading to behavioral changes in mice. Magnetoelectric materials present a versatile platform technology for less invasive, deep brain neuromodulation.

scholarly journals In vivo validation of a new portable stimulator for chronic deep brain stimulation in freely moving rats

2020 ◽  
Vol 333 ◽  
pp. 108577
Author(s):  
Houyam Tibar ◽  
Frédéric Naudet ◽  
Florian Kölbl ◽  
Bastien Ribot ◽  
Emilie Faggiani ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Freely Moving Rats ◽  
Freely Moving ◽  
Deep Brain ◽  
In Vivo Validation

scholarly journals Large-scale recording of thalamocortical circuits: in vivo electrophysiology with the two-dimensional electronic depth control silicon probe

2016 ◽  
Vol 116 (5) ◽  
pp. 2312-2330 ◽  
Author(s):  
Richárd Fiáth ◽  
Patrícia Beregszászi ◽  
Domonkos Horváth ◽  
Lucia Wittner ◽  
Arno A. A. Aarts ◽  
...  
Keyword(s):  
Large Scale ◽  
Complementary Metal Oxide Semiconductor ◽  
Oxide Semiconductor ◽  
Electrophysiological Recording ◽  
Multielectrode Arrays ◽  
Two Dimensional ◽  
Single Experiment ◽  
Brain Functions ◽  
Depth Control

Recording simultaneous activity of a large number of neurons in distributed neuronal networks is crucial to understand higher order brain functions. We demonstrate the in vivo performance of a recently developed electrophysiological recording system comprising a two-dimensional, multi-shank, high-density silicon probe with integrated complementary metal-oxide semiconductor electronics. The system implements the concept of electronic depth control (EDC), which enables the electronic selection of a limited number of recording sites on each of the probe shafts. This innovative feature of the system permits simultaneous recording of local field potentials (LFP) and single- and multiple-unit activity (SUA and MUA, respectively) from multiple brain sites with high quality and without the actual physical movement of the probe. To evaluate the in vivo recording capabilities of the EDC probe, we recorded LFP, MUA, and SUA in acute experiments from cortical and thalamic brain areas of anesthetized rats and mice. The advantages of large-scale recording with the EDC probe are illustrated by investigating the spatiotemporal dynamics of pharmacologically induced thalamocortical slow-wave activity in rats and by the two-dimensional tonotopic mapping of the auditory thalamus. In mice, spatial distribution of thalamic responses to optogenetic stimulation of the neocortex was examined. Utilizing the benefits of the EDC system may result in a higher yield of useful data from a single experiment compared with traditional passive multielectrode arrays, and thus in the reduction of animals needed for a research study.

scholarly journals MAPSSIC, a communicating MAPS-based intracerebral positrons probe for deep brain imaging in awake and freely-moving rats

2020 ◽  
Vol 225 ◽  
pp. 09002
Author(s):  
F. Gensolen ◽  
L. Ammour ◽  
M. Bautista ◽  
J. Heymes ◽  
S. Fieux ◽  
...  
Keyword(s):  
Human Brain ◽  
Neural Mechanisms ◽  
Small Animals ◽  
Biological Mechanisms ◽  
Behavioral Experiments ◽  
Freely Moving ◽  
The Brain ◽  
Significant Model ◽  
Deep Brain

Radioisotope imaging is a powerful tool to understand the biological mechanisms in-vivo, especially in the brain of small animals, providing a significant model to study the human brain. In this context, we have developed and built a pixelated intracerebral positron probe to be embedded on awake and freely moving small animals, typically rats. This pixelated probe will represent a key instrument for neuroscientists to study neural mechanisms and correlate them to behavioral experiments. We describe in this paper the simulations carried out to design the intracerebral sensor, its architecture, and the detection of positrons in a volume with a couple of sensors assembled back-to-back. We also depict the architecture of the wireless acquisition system. Finally, we present the first measurements performed in real-time by this miniaturized probe with sealed radioactive sources and a 18F solution.

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