scholarly journals Simultaneous optogenetic manipulation and calcium imaging in freely movingC. elegans

2013 ◽  
Author(s):  
Frederick B. Shipley ◽  
Christopher M. Clark ◽  
Mark J. Alkema ◽  
Andrew M. Leifer
Keyword(s):  
Neural Activity ◽  
Calcium Imaging ◽  
Neural Circuits ◽  
Neural Response ◽  
Sensory Stimuli ◽  
Systems Neuroscience ◽  
C Elegans ◽  
Fundamental Goal ◽  
Freely Moving ◽  
Interneuron Activity

A fundamental goal of systems neuroscience is to probe the dynamics of neural activity that drive behavior. Here we present an instrument to simultaneously manipulate neural activity via Channelrhodopsin, monitor neural response via GCaMP3, and observes behavior in freely moving C. elegans. We use the instrument to directly observe the relation between sensory stimuli, interneuron activity and locomotion in the mechanosensory circuit. Now published as: Front Neural Circuits 8:28, doi:10.3389/fncir.2014.00028

scholarly journals A novel device for real-time measurement and manipulation of licking behavior in head-fixed mice

2018 ◽  
Vol 120 (6) ◽  
pp. 2975-2987 ◽  
Author(s):  
Brice Williams ◽  
Anderson Speed ◽  
Bilal Haider
Keyword(s):  
Real Time ◽  
Neural Activity ◽  
Closed Loop ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Visual Behavior ◽  
Sensory Stimuli ◽  
Neural Recordings ◽  
Control Signals ◽  
Sensory Motor

The mouse has become an influential model system for investigating the mammalian nervous system. Technologies in mice enable recording and manipulation of neural circuits during tasks where they respond to sensory stimuli by licking for liquid rewards. Precise monitoring of licking during these tasks provides an accessible metric of sensory-motor processing, particularly when combined with simultaneous neural recordings. There are several challenges in designing and implementing lick detectors during head-fixed neurophysiological experiments in mice. First, mice are small, and licking behaviors are easily perturbed or biased by large sensors. Second, neural recordings during licking are highly sensitive to electrical contact artifacts. Third, submillisecond lick detection latencies are required to generate control signals that manipulate neural activity at appropriate time scales. Here we designed, characterized, and implemented a contactless dual-port device that precisely measures directional licking in head-fixed mice performing visual behavior. We first determined the optimal characteristics of our detector through design iteration and then quantified device performance under ideal conditions. We then tested performance during head-fixed mouse behavior with simultaneous neural recordings in vivo. We finally demonstrate our device’s ability to detect directional licks and generate appropriate control signals in real time to rapidly suppress licking behavior via closed-loop inhibition of neural activity. Our dual-port detector is cost effective and easily replicable, and it should enable a wide variety of applications probing the neural circuit basis of sensory perception, motor action, and learning in normal and transgenic mouse models. NEW & NOTEWORTHY Mice readily learn tasks in which they respond to sensory cues by licking for liquid rewards; tasks that involve multiple licking responses allow study of neural circuits underlying decision making and sensory-motor integration. Here we design, characterize, and implement a novel dual-port lick detector that precisely measures directional licking in head-fixed mice performing visual behavior, enabling simultaneous neural recording and closed-loop manipulation of licking.

scholarly journals A distributed neural code in the dentate gyrus and in CA1

2018 ◽  
Author(s):  
Fabio Stefanini ◽  
Mazen A. Kheirbek ◽  
Lyudmila Kushnir ◽  
Jessica Jimenez ◽  
Joshua H. Jennings ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Calcium Imaging ◽  
Neural Circuits ◽  
Population Analysis ◽  
Neural Code ◽  
Response Properties ◽  
Instantaneous Position ◽  
Relevant Variables ◽  
Freely Moving ◽  
Single Cell Response

ABSTRACTThe tuning properties of neurons in a given brain region have been traditionally viewed as the under-pinnings of computation in neural circuits. However, at the higher levels of processing, specialization is often elusive, instead a mix of sensory, cognitive and behavioural quantities drive neural activity. In such networks, ensembles of neurons, rather than single units with easily interpretable tuning properties, encode behaviourally relevant variables. Here we show that this is the case also in the dentate gyrus and CA1 subregions of the hippocampus. Using calcium imaging in freely moving mice, we decoded the instantaneous position, direction of motion and speed from the activity of hundreds of cells in the hippocampus of mice freely exploring an arena. For the vast majority of neurons in both regions, their response properties were not predictive of their importance for encoding position. Furthermore, we could decode position from populations of cells that were important for decoding direction of motion and vice versa, showing that these quantities are encoded by largely overlapping ensembles as in distributed neural code. Finally, we found that correlated activities had an impact on decoding performance in CA1 but not in dentate gyrus, suggesting different enconding strategies for these areas. Our analysis indicates that classical methods of analysis based on single cell response properties might be insufficient to accurately characterize the neural computation in a given area. In contrast, population analysis may help highlight previously overlooked properties of hippocampal circuits.

scholarly journals All-optical imaging and patterned stimulation with a one-photon endoscope

2021 ◽  
Author(s):  
Jinyong Zhang ◽  
Ryan N Hughes ◽  
Namsoo Kim ◽  
Isabella P Fallon ◽  
Konstantin I bakhurin ◽  
...  
Keyword(s):  
Neural Activity ◽  
Calcium Imaging ◽  
Neural Circuit ◽  
Integrated System ◽  
Striatal Neurons ◽  
Indirect Pathway ◽  
Cellular Resolution ◽  
All Optical ◽  
Freely Moving

While in vivo calcium imaging makes it possible to record activity in defined neuronal populations with cellular resolution, optogenetics allows selective manipulation of neural activity. Recently, these two tools have been combined to stimulate and record neural activity at the same time, but current approaches often rely on two-photon microscopes that are difficult to use in freely moving animals. To address these limitations, we have developed a new integrated system combining a one-photon endoscope and a digital micromirror device for simultaneous calcium imaging and precise optogenetic photo-stimulation with near cellular resolution (Miniscope with All-optical Patterned Stimulation and Imaging, MAPSI). Using this highly portable system in freely moving mice, we were able to image striatal neurons from either the direct pathway or the indirect pathway while simultaneously activating any neuron of choice in the field of view, or to synthesize arbitrary spatiotemporal patterns of photo-stimulation. We could also select neurons based on their relationship with behavior and recreate the behavior by mimicking the natural neural activity with photo-stimulation. MAPSI thus provides a powerful tool for interrogation of neural circuit function in freely moving animals.

The C. elegans homeodomain gene unc-42 regulates chemosensory and glutamate receptor expression

Development ◽  
1999 ◽  
Vol 126 (10) ◽  
pp. 2241-2251 ◽  
Author(s):  
R. Baran ◽  
R. Aronoff ◽  
G. Garriga
Keyword(s):  
Axon Guidance ◽  
Cell Fate ◽  
Glutamate Receptor ◽  
Sensory Neurons ◽  
Motor Neurons ◽  
Neural Circuits ◽  
Receptor Expression ◽  
Homeodomain Protein ◽  
Sensory Stimuli ◽  
C Elegans

Genes that specify cell fate can influence multiple aspects of neuronal differentiation, including axon guidance, target selection and synapse formation. Mutations in the unc-42 gene disrupt axon guidance along the C. elegans ventral nerve cord and cause distinct functional defects in sensory-locomotory neural circuits. Here we show that unc-42 encodes a novel homeodomain protein that specifies the fate of three classes of neurons in the Caenorhabditis elegans nervous system: the ASH polymodal sensory neurons, the AVA, AVD and AVE interneurons that mediate repulsive sensory stimuli to the nematode head and anterior body, and a subset of motor neurons that innervate head and body-wall muscles. unc-42 is required for the expression of cell-surface receptors that are essential for the mature function of these neurons. In mutant animals, the ASH sensory neurons fail to express SRA-6 and SRB-6, putative chemosensory receptors. The AVA, AVD and AVE interneurons and RME and RMD motor neurons of unc-42 mutants similarly fail to express the GLR-1 glutamate receptor. These results show that unc-42 performs an essential role in defining neuron identity and contributes to the establishment of neural circuits in C. elegans by regulating the transcription of glutamate and chemosensory receptor genes.

scholarly journals Distinct neural circuits establish the same chemosensory behavior in C. elegans

2021 ◽  
Author(s):  
Navonil Banerjee ◽  
Pei-Yin Shih ◽  
Elisa J. Rojas Palato ◽  
Paul W. Sternberg ◽  
Elissa A. Hallem
Keyword(s):  
Neural Circuits ◽  
Life Stage ◽  
Neural Mechanisms ◽  
Life Stages ◽  
C Elegans ◽  
Evoked Activity ◽  
Molecular Signals ◽  
Dauer Larvae ◽  
Chemosensory Behavior ◽  
Interneuron Activity

AbstractAnimals frequently exhibit the same behavior under different environmental or physiological conditions. To what extent these behaviors are generated by similar vs. distinct mechanisms is unclear. Moreover, the circumstances under which divergent neural mechanisms establish the same behavior, and the molecular signals that regulate the same behavior across conditions, are poorly understood. We show that in C. elegans, distinct neural mechanisms mediate the same chemosensory behavior at two different life stages. Both dauer larvae and starved adults are attracted to carbon dioxide (CO2), but CO2 attraction is mediated by distinct sets of interneurons at the two life stages. Some interneurons mediate CO2 response only in dauers, some show CO2-evoked activity in adults and dauers but contribute to CO2 response only in adults, and some show CO2-evoked activity that opposes CO2 attraction in adults but promotes CO2 attraction in dauers. We also identify a novel role for insulin signaling in establishing life-stage-specific CO2 responses by modulating interneuron activity. Further, we show that a combinatorial code of both shared and life-stage-specific molecular signals regulate CO2 attraction. Our results identify a mechanism by which the same chemosensory behavior can be generated by distinct neural circuits, revealing an unexpected complexity to chemosensory processing.

scholarly journals Ramp-to-Threshold Dynamics in a Hindbrain Population Controls the Timing of Spontaneous Saccades

2018 ◽  
Author(s):  
Alexandro D. Ramirez ◽  
Emre R.F. Aksay
Keyword(s):  
Calcium Imaging ◽  
Neural Circuits ◽  
Threshold Model ◽  
Activity Patterns ◽  
Threshold Dynamics ◽  
Sensory Stimuli ◽  
Larval Zebrafish ◽  
The Times ◽  
Population Controls ◽  
Made In

SummaryOrganisms have the capacity to make decisions based solely on internal drives. However, it is unclear how neural circuits form decisions in the absence of sensory stimuli. Here we provide a comprehensive map of the activity patterns underlying the generation of saccades made in the absence of visual stimuli. We performed calcium imaging in the larval zebrafish to discover a range of responses surrounding spontaneous saccades, from cells that displayed tonic discharge only during fixations to neurons whose activity rose in advance of saccades by multiple seconds. We lesioned cells in these populations and found that ablation of neurons with pre-saccadic rise delayed saccade initiation. We analyzed spontaneous saccade initiation using a ramp-to-threshold model and were able to predict the times of upcoming saccades using pre-saccadic activity. These findings suggest that ramping of neuronal activity to a bound is a critical component of self-initiated saccadic movements.

scholarly journals Automated long-term recording and analysis of neural activity in behaving animals

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Ashesh K Dhawale ◽  
Rajesh Poddar ◽  
Steffen BE Wolff ◽  
Valentin A Normand ◽  
Evi Kopelowitz ◽  
...  
Keyword(s):  
Neural Activity ◽  
Neural Circuits ◽  
Large Datasets ◽  
Neural Dynamics ◽  
Single Unit Activity ◽  
Firing Rates ◽  
Freely Moving ◽  
Automated Platform ◽  
And Behavior

Addressing how neural circuits underlie behavior is routinely done by measuring electrical activity from single neurons in experimental sessions. While such recordings yield snapshots of neural dynamics during specified tasks, they are ill-suited for tracking single-unit activity over longer timescales relevant for most developmental and learning processes, or for capturing neural dynamics across different behavioral states. Here we describe an automated platform for continuous long-term recordings of neural activity and behavior in freely moving rodents. An unsupervised algorithm identifies and tracks the activity of single units over weeks of recording, dramatically simplifying the analysis of large datasets. Months-long recordings from motor cortex and striatum made and analyzed with our system revealed remarkable stability in basic neuronal properties, such as firing rates and inter-spike interval distributions. Interneuronal correlations and the representation of different movements and behaviors were similarly stable. This establishes the feasibility of high-throughput long-term extracellular recordings in behaving animals.

scholarly journals Three-dimensional Two-Photon Optogenetics and Imaging of Neural Circuits in vivo

2017 ◽  
Author(s):  
Weijian Yang ◽  
Luis Carrillo-Reid ◽  
Yuki Bando ◽  
Darcy S. Peterka ◽  
Rafael Yuste
Keyword(s):  
Visual Cortex ◽  
Neural Activity ◽  
Calcium Imaging ◽  
Pyramidal Neurons ◽  
Neural Circuits ◽  
Three Dimensional ◽  
Two Photon ◽  
Cellular Resolution ◽  
Photon Excitation

We demonstrate a holographic system for simultaneous three-dimensional (3D) two-photon stimulation and imaging of neural activity in the mouse neocortex in vivo with cellular resolution. Dual two-photon excitation paths are implemented with independent 3D targeting for calcium imaging and precision optogenetics. We validate the usefulness of the microscope by photoactivating local pools of interneurons in awake mice visual cortex in 3D, which suppress the nearby pyramidal neurons’ response to visual stimuli.

scholarly journals Simultaneous optogenetic manipulation and calcium imaging in freely moving C. elegans

2014 ◽  
Vol 8 ◽  
Author(s):  
Frederick B. Shipley ◽  
Christopher M. Clark ◽  
Mark J. Alkema ◽  
Andrew M. Leifer
Keyword(s):  
Calcium Imaging ◽  
C Elegans ◽  
Freely Moving

scholarly journals Chronically implanted Neuropixels probes enable high-yield recordings in freely moving mice

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Ashley L Juavinett ◽  
George Bekheet ◽  
Anne K Churchland
Keyword(s):  
Neural Activity ◽  
Neural Circuits ◽  
High Yield ◽  
High Signal ◽  
Signal To Noise ◽  
Novel Device ◽  
Approaches To Study ◽  
Freely Moving

The advent of high-yield electrophysiology using Neuropixels probes is now enabling researchers to simultaneously record hundreds of neurons with remarkably high signal to noise. However, these probes have not been well-suited to use in freely moving mice. It is critical to study neural activity in unrestricted animals for many reasons, such as leveraging ethological approaches to study neural circuits. We designed and implemented a novel device that allows Neuropixels probes to be customized for chronically implanted experiments in freely moving mice. We demonstrate the ease and utility of this approach in recording hundreds of neurons during an ethological behavior across weeks of experiments. We provide the technical drawings and procedures for other researchers to do the same. Importantly, our approach enables researchers to explant and reuse these valuable probes, a transformative step which has not been established for recordings with any type of chronically-implanted probe.

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