scholarly journals Large-scale all-optical dissection of motor cortex connectivity reveals a segregated functional organization of mouse forelimb representations

2021 ◽  
Author(s):  
Francesco Resta ◽  
Elena Montagni ◽  
Giuseppe de Vito ◽  
Alessandro Scaglione ◽  
Anna Letizia Allegra Mascaro ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Large Scale ◽  
Functional Organization ◽  
Voluntary Movements ◽  
Motor Representation ◽  
Activation Patterns ◽  
Optogenetic Stimulation ◽  
All Optical ◽  
The Brain ◽  
Stimulation Of

In rodent motor cortex, the rostral forelimb area (RFA) and the caudal forelimb area (CFA) are major actors in orchestrating the control of forelimb complex movements. However, their intrinsic connections and reciprocal functional organization are still unclear, limiting our understanding of how the brain coordinates and executes voluntary movements. Here we causally probed cortical connectivity and activation patterns triggered by transcranial optogenetic stimulation of ethologically relevant complex movements exploiting a novel large-scale all-optical method in awake mice. Results show specific activation features for each movement class, providing evidence for a segregated functional organization of CFA and RFA. Importantly, we identified a second discrete lateral grasping representation area, namely lateral forelimb area (LFA), with unique connectivity and activation patterns. Therefore, we propose the LFA as a distinct motor representation in the forelimb somatotopic motor map.

scholarly journals Coordination of brain wide activity dynamics by dopaminergic neurons

2016 ◽  
Author(s):  
Garret Stuber ◽  
Heather Decot ◽  
Vijay Namboodiri ◽  
Wei Gao ◽  
Jenna McHenry ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Large Scale ◽  
Cerebral Blood Volume ◽  
Brain Activity ◽  
Functional Magnetic Resonance ◽  
Transgenic Rats ◽  
Optogenetic Stimulation ◽  
The Brain ◽  
Neuropsychiatric Conditions ◽  
Stimulation Of

Several neuropsychiatric conditions, such as addiction, schizophrenia, and depression may arise in part from dysregulated activity of ventral tegmental area dopaminergic (THVTA) neurons, as well as from more global maladaptation in neurocircuit function. However, whether THVTA activity affects large-scale brain-wide function remains unknown. Here, we selectively activated THVTA neurons in transgenic rats and measured resulting changes in whole-brain activity using stimulus-evoked functional magnetic resonance imaging (fMRI). Selective optogenetic stimulation of THVTA neurons not only enhanced cerebral blood volume (CBV) signals in striatal target regions in a dopamine receptor dependent fashion, but also engaged many additional anatomically defined regions throughout the brain. In addition, repeated pairing of THVTA neuronal activity with forepaw stimulation, produced an expanded brain-wide sensory representation. These data suggest that modulation of THVTA neurons can impact brain dynamics across many distributed anatomically distinct regions, even those that receive little to no direct THVTA input.

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.

Striatal dopamine mediates hallucination-like perception in mice

Science ◽  
2021 ◽  
Vol 372 (6537) ◽  
pp. eabf4740
Author(s):  
K. Schmack ◽  
M. Bosc ◽  
T. Ott ◽  
J. F. Sturgill ◽  
A. Kepecs
Keyword(s):  
Psychotic Disorders ◽  
Neural Circuit ◽  
Dopamine Neurons ◽  
Striatal Dopamine ◽  
Model Organisms ◽  
High Confidence ◽  
Optogenetic Stimulation ◽  
The Brain ◽  
Central Symptom ◽  
Stimulation Of

Hallucinations, a central symptom of psychotic disorders, are attributed to excessive dopamine in the brain. However, the neural circuit mechanisms by which dopamine produces hallucinations remain elusive, largely because hallucinations have been challenging to study in model organisms. We developed a task to quantify hallucination-like perception in mice. Hallucination-like percepts, defined as high-confidence false detections, increased after hallucination-related manipulations in mice and correlated with self-reported hallucinations in humans. Hallucination-like percepts were preceded by elevated striatal dopamine levels, could be induced by optogenetic stimulation of mesostriatal dopamine neurons, and could be reversed by the antipsychotic drug haloperidol. These findings reveal a causal role for dopamine-dependent striatal circuits in hallucination-like perception and open new avenues to develop circuit-based treatments for psychotic disorders.

scholarly journals Effective intracortical microstimulation parameters applied to primary motor cortex for evoking forelimb movements to stable spatial end points

2013 ◽  
Vol 110 (5) ◽  
pp. 1180-1189 ◽  
Author(s):  
Gustaf M. Van Acker ◽  
Sommer L. Amundsen ◽  
William G. Messamore ◽  
Hongyu Y. Zhang ◽  
Carl W. Luchies ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Large Scale ◽  
Primary Motor Cortex ◽  
Emg Activity ◽  
Intracortical Microstimulation ◽  
End Points ◽  
End Point ◽  
Motor Effects ◽  
Forelimb Movements ◽  
Stimulation Of

High-frequency, long-duration intracortical microstimulation (HFLD-ICMS) applied to motor cortex is recognized as a useful and informative method for corticomotor mapping by evoking natural-appearing movements of the limb to consistent stable end-point positions. An important feature of these movements is that stimulation of a specific site in motor cortex evokes movement to the same spatial end point regardless of the starting position of the limb. The goal of this study was to delineate effective stimulus parameters for evoking forelimb movements to stable spatial end points from HFLD-ICMS applied to primary motor cortex (M1) in awake monkeys. We investigated stimulation of M1 as combinations of frequency (30–400 Hz), amplitude (30–200 μA), and duration (0.5–2 s) while concurrently recording electromyographic (EMG) activity from 24 forelimb muscles and movement kinematics with a motion capture system. Our results suggest a range of parameters (80–140 Hz, 80–140 μA, and 1,000-ms train duration) that are effective and safe for evoking forelimb translocation with subsequent stabilization at a spatial end point. The mean time for stimulation to elicit successful movement of the forelimb to a stable spatial end point was 475.8 ± 170.9 ms. Median successful frequency and amplitude were 110 Hz and 110 μA, respectively. Attenuated parameters resulted in inconsistent, truncated, or undetectable movements, while intensified parameters yielded no change to movement end points and increased potential for large-scale physiological spread and adverse focal motor effects. Establishing cortical stimulation parameters yielding consistent forelimb movements to stable spatial end points forms the basis for a systematic and comprehensive mapping of M1 in terms of evoked movements and associated muscle synergies. Additionally, the results increase our understanding of how the central nervous system may encode movement.

scholarly journals Optogenetic Stimulation Reduces Neuronal Nitric Oxide Synthase Expression After Stroke

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Arjun Vivek Pendharkar ◽  
Daniel L Smerin ◽  
Lorenzo Gonzales ◽  
Eric Wang ◽  
Sabrina L Levy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Motor Cortex ◽  
Functional Recovery ◽  
Neuronal Nitric Oxide Synthase ◽  
Optogenetic Stimulation ◽  
Oxide Synthase ◽  
Nnos Expression ◽  
Stimulation Of ◽  
Nnos Inhibition

Abstract INTRODUCTION Poststroke optogenetic stimulation has been shown to enhance neurovascular coupling and functional recovery. Neuronal nitric oxide synthase (nNOS) has been implicated as a key regulator of neurovascular response in acute stroke but its role in subacute recovery remains unclear. Here we investigate nNOS expression in stroke mice undergoing optogenetic stimulation of the contralesional lateral cerebellar nucleus (cLCN). We also examine the effects of nNOS inhibition on functional recovery using a pharmacological inhibitor targeting nNOS. METHODS Transgenic Thy1-ChR2-YFP male mice (10-12 wk) were used. Stereotaxic surgery was performed to implant a fiber cannula in the cLCN and animals underwent intraluminal middle cerebral artery suture occlusion (30 min). Optogenetic stimulation began at poststroke (PD) day 5 and continued until PD14. Sensorimotor tests were used to assess behavioral recovery at PD4, 7, 10, and 14. At PD15, primary motor cortex from both ipsi- and contralesional motor cortex (iM1, cM1) were dissected. nNOS mRNA and protein levels were examined using quantitative polymerase chain reaction and western blot. In another set of studies, nNOS inhibitor ARL 17477 dihydrochloride (10 mg/kg, intraperitoneally) was administered daily between PD5-14 and functional recovery was evaluated using sensorimotor tests. RESULTS cLCN stimulated stroke mice demonstrated significant improvement in speed (cm/s) on the rotating beam task at PD10 and 14 day (P < .05, P < .001 respectively). nNOS mRNA and protein expression was significantly and selectively decreased in cM1 of cLCN stimulated mice (P < .05). The reduced nNOS expression in cM1 was negatively correlated with improved recovery (R2 = −0.839, Pearson P = .009). nNOS inhibitor-treated stroke mice exhibited a significant functional improvement in speed at PD10, when compared to stroke mice receiving vehicle (saline) (P < .05). CONCLUSION Our results suggest that nNOS may play a maladaptive role in poststroke recovery. Optogenetic stimulation of cLCN and systemic nNOS inhibition produce functional benefits after stroke.

scholarly journals Parylene photonics: a flexible, broadband optical waveguide platform with integrated micromirrors for biointerfaces

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Jay W. Reddy ◽  
Maya Lassiter ◽  
Maysamreza Chamanzar
Keyword(s):  
Optical Waveguides ◽  
Brain Activity ◽  
Low Loss ◽  
Parylene C ◽  
Optogenetic Stimulation ◽  
Patterned Illumination ◽  
The Brain ◽  
532 Nm ◽  
Stimulation Of

Abstract Targeted light delivery into biological tissue is needed in applications such as optogenetic stimulation of the brain and in vivo functional or structural imaging of tissue. These applications require very compact, soft, and flexible implants that minimize damage to the tissue. Here, we demonstrate a novel implantable photonic platform based on a high-density, flexible array of ultracompact (30 μm × 5 μm), low-loss (3.2 dB/cm at λ = 680 nm, 4.1 dB/cm at λ = 633 nm, 4.9 dB/cm at λ = 532 nm, 6.1 dB/cm at λ = 450 nm) optical waveguides composed of biocompatible polymers Parylene C and polydimethylsiloxane (PDMS). This photonic platform features unique embedded input/output micromirrors that redirect light from the waveguides perpendicularly to the surface of the array for localized, patterned illumination in tissue. This architecture enables the design of a fully flexible, compact integrated photonic system for applications such as in vivo chronic optogenetic stimulation of brain activity.

scholarly journals Arm movements induced by noninvasive optogenetic stimulation of the motor cortex in the common marmoset

2019 ◽  
Vol 116 (45) ◽  
pp. 22844-22850 ◽  
Author(s):  
Teppei Ebina ◽  
Keitaro Obara ◽  
Akiya Watakabe ◽  
Yoshito Masamizu ◽  
Shin-Ichiro Terada ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Nonhuman Primates ◽  
Arm Movements ◽  
Common Marmoset ◽  
Blue Laser ◽  
Optogenetic Stimulation ◽  
Long Duration ◽  
The Common ◽  
Forelimb Movements ◽  
Stimulation Of

Optogenetics is now a fundamental tool for investigating the relationship between neuronal activity and behavior. However, its application to the investigation of motor control systems in nonhuman primates is rather limited, because optogenetic stimulation of cortical neurons in nonhuman primates has failed to induce or modulate any hand/arm movements. Here, we used a tetracycline-inducible gene expression system carrying CaMKII promoter and the gene encoding a Channelrhodopsin-2 variant with fast kinetics in the common marmoset, a small New World monkey. In an awake state, forelimb movements could be induced when Channelrhodopsin-2−expressing neurons in the motor cortex were illuminated by blue laser light with a spot diameter of 1 mm or 2 mm through a cranial window without cortical invasion. Forelimb muscles responded 10 ms to 50 ms after photostimulation onset. Long-duration (500 ms) photostimulation induced discrete forelimb movements that could be markerlessly tracked with charge-coupled device cameras and a deep learning algorithm. Long-duration photostimulation mapping revealed that the primary motor cortex is divided into multiple domains that can induce hand and elbow movements in different directions. During performance of a forelimb movement task, movement trajectories were modulated by weak photostimulation, which did not induce visible forelimb movements at rest, around the onset of task-relevant movement. The modulation was biased toward the movement direction induced by the strong photostimulation. Combined with calcium imaging, all-optical interrogation of motor circuits should be possible in behaving marmosets.

scholarly journals Dissociable effects of local inhibitory and excitatory theta-burst stimulation on large-scale brain dynamics

2015 ◽  
Vol 113 (9) ◽  
pp. 3375-3385 ◽  
Author(s):  
Luca Cocchi ◽  
Martin V. Sale ◽  
Anton Lord ◽  
Andrew Zalesky ◽  
Michael Breakspear ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Large Scale ◽  
Dynamic Balance ◽  
Normal Brain ◽  
Human Motor Cortex ◽  
Normal Brain Function ◽  
Large Scale Integration ◽  
Internal Integration ◽  
Scale Integration ◽  
Stimulation Of

Normal brain function depends on a dynamic balance between local specialization and large-scale integration. It remains unclear, however, how local changes in functionally specialized areas can influence integrated activity across larger brain networks. By combining transcranial magnetic stimulation with resting-state functional magnetic resonance imaging, we tested for changes in large-scale integration following the application of excitatory or inhibitory stimulation on the human motor cortex. After local inhibitory stimulation, regions encompassing the sensorimotor module concurrently increased their internal integration and decreased their communication with other modules of the brain. There were no such changes in modular dynamics following excitatory stimulation of the same area of motor cortex nor were there changes in the configuration and interactions between core brain hubs after excitatory or inhibitory stimulation of the same area. These results suggest the existence of selective mechanisms that integrate local changes in neural activity, while preserving ongoing communication between brain hubs.

scholarly journals Distributed affective space represents multiple emotion categories across the brain

2017 ◽  
Author(s):  
Heini Saarimäki ◽  
Lara Farzaneh Ejtehadian ◽  
Enrico Glerean ◽  
liro P. Jääskeläinen ◽  
Patrik Vuilleumier ◽  
...  
Keyword(s):  
Functional Organization ◽  
Brain Activity ◽  
Premotor Cortex ◽  
Subjective Feeling ◽  
Neural Activation ◽  
Functional Magnetic Resonance ◽  
Activation Patterns ◽  
Discrete Emotion ◽  
Subcortical Regions ◽  
The Brain

The functional organization of human emotion systems as well as their neuroanatomical basis and segregation in the brain remains unresolved. Here we used pattern classification and hierarchical clustering to reveal and characterize the organization of discrete emotion categories in the human brain. We induced 14 emotions (6 “basic”, such as fear and anger; and 8 “non-basic”, such as shame and gratitude) and a neutral state in participants using guided mental imagery while their brain activity was measured with functional magnetic resonance imaging (fMRI). Twelve out of 14 emotions could be reliably classified from the fMRI signals. All emotions engaged a multitude of brain areas, primarily in midline cortices including anterior and posterior cingulate and precuneus, in subcortical regions, and in motor regions including cerebellum and premotor cortex. Similarity of subjective emotional experiences was associated with similarity of the corresponding neural activation patterns. We conclude that the emotions included in the study have discrete neural bases characterized by specific, distributed activation patterns in widespread cortical and subcortical circuits, and highlight both overlaps and differences in the locations of these for each emotion. Locally differentiated engagement of these globally shared circuits defines the unique neural fingerprint activity pattern and the corresponding subjective feeling associated with each emotion.

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