scholarly journals Simultaneous mesoscopic and two-photon imaging of neuronal activity in cortical circuits

2018 ◽  
Author(s):  
D Barson ◽  
AS Hamodi ◽  
X Shen ◽  
G Lur ◽  
RT Constable ◽  
...  
Keyword(s):  
Calcium Imaging ◽  
Spatial Scales ◽  
Cortical Circuits ◽  
Orthogonal Axis ◽  
Two Photon ◽  
Evoked Activity ◽  
Sensory Evoked ◽  
Local Circuits ◽  
The Brain ◽  
Juvenile Mouse

AbstractSpontaneous and sensory-evoked activity propagates across spatial scales in the mammalian cortex but technical challenges have generally precluded establishing conceptual links between the function of local circuits of neurons and brain-wide network dynamics. To solve this problem, we developed a method for simultaneous cellular-resolution two-photon calcium imaging of a local microcircuit and mesoscopic widefield calcium imaging of the entire cortical mantle in awake, behaving mice. Our method employs an orthogonal axis design whereby the mesoscopic objective is oriented downward directly above the brain and the two-photon objective is oriented horizontally, with imaging performed through a glass right angle microprism implanted in the skull. In support of this method, we introduce a suite of analysis tools for relating the activity of individual cells to distal cortical areas, as well as a viral method for robust and widespread gene delivery in the juvenile mouse brain. We use these methods to characterize the diversity of associations of individual, genetically-defined neurons with cortex-wide network motifs.

scholarly journals Widespread inhibition, antagonism, and synergy in mouse olfactory sensory neurons in vivo

2019 ◽  
Author(s):  
Shigenori Inagaki ◽  
Ryo Iwata ◽  
Masakazu Iwamoto ◽  
Takeshi Imai
Keyword(s):  
Sensory Neurons ◽  
Calcium Imaging ◽  
Odorant Receptor ◽  
Sensory Information ◽  
Olfactory Sensory Neurons ◽  
Axon Terminals ◽  
Two Photon ◽  
Odor Mixtures ◽  
The Brain

SUMMARYSensory information is selectively or non-selectively inhibited and enhanced in the brain, but it remains unclear whether this occurs commonly at the peripheral stage. Here, we performed two-photon calcium imaging of mouse olfactory sensory neurons (OSNs) in vivo and found that odors produce not only excitatory but also inhibitory responses at their axon terminals. The inhibitory responses remained in mutant mice, in which all possible sources of presynaptic lateral inhibition were eliminated. Direct imaging of the olfactory epithelium revealed widespread inhibitory responses at OSN somata. The inhibition was in part due to inverse agonism toward the odorant receptor. We also found that responses to odor mixtures are often suppressed or enhanced in OSNs: Antagonism was dominant at higher odor concentrations, whereas synergy was more prominent at lower odor concentrations. Thus, odor responses are extensively tuned by inhibition, antagonism, and synergy, at the early peripheral stage, contributing to robust odor representations.

scholarly journals Cellular precision of orientation and spatial frequency maps in macaque V1

2019 ◽  
Author(s):  
Nian-Sheng Ju ◽  
Shu-Chen Guan ◽  
Shi-Ming Tang ◽  
Cong Yu
Keyword(s):  
Spatial Frequency ◽  
Calcium Imaging ◽  
Functional Organization ◽  
Neuronal Response ◽  
Guiding Principle ◽  
Two Photon ◽  
Frequency Branch ◽  
Geometric Relationship ◽  
The Brain ◽  
Specific Orientation

AbstractFunctional organization of neuronal response properties along the surface of the neocortex is a fundamental guiding principle of neural computation in the brain. Despite this importance, the cellular precision of functional maps is still largely unknown. We address the challenge by using two-photon calcium imaging to measure cell-specific orientation and spatial frequency (SF) responses across fields of macaque V1 superficial layers. The cellular orientation maps confirm iso-orientation domains, but rarely show pinwheels. Pinwheels obtained through conventional Gaussian smoothing and vector summation of orientation responses mostly overlap with blood vessel regions, suggesting false singularities. Cellular SF maps clarify existing controversies by showing weak iso-frequency clusters, which also suggests a weak geometric relationship between orientation and SF maps. Most neurons are tuned to medium frequencies, but the tuning functions are often asymmetric with a wider low- or high-frequency branch, which may help encode low or high SF information for later decoding.

scholarly journals Multi-functional feedforward inhibitory circuits for cortical odor processing

2021 ◽  
Author(s):  
Norimitsu Suzuki ◽  
Malinda L. S. Tantirigama ◽  
Helena H.-Y. Huang ◽  
John M. Bekkers
Keyword(s):  
Calcium Imaging ◽  
Piriform Cortex ◽  
Complex Interplay ◽  
Inhibitory Circuits ◽  
Two Photon ◽  
Odor Processing ◽  
Strong Excitation ◽  
The Brain ◽  
Feedforward Inhibition

Feedforward inhibitory circuits are key contributors to the complex interplay between excitation and inhibition in the brain. Little is known about the function of feedforward inhibition in the primary olfactory (piriform) cortex. Using in vivo two-photon targeted patch clamping and calcium imaging in mice, we find that odors evoke strong excitation in two classes of interneurons – neurogliaform (NG) cells and horizontal (HZ) cells – that provide feedforward inhibition in layer 1 of the piriform cortex. NG cells fire much earlier than HZ cells following odor onset, a difference that can be attributed to the faster odor-driven excitatory synaptic drive that NG cells receive from the olfactory bulb. As a consequence, NG cells strongly but transiently inhibit odor-evoked excitation in layer 2 principal cells, whereas HZ cells provide more diffuse and prolonged feedforward inhibition. Our findings reveal unexpected complexity in the operation of inhibition in the piriform cortex.

scholarly journals Cortical subnetworks encode context of visual stimulus

2018 ◽  
Author(s):  
Jordan P. Hamm ◽  
Yuriy Shymkiv ◽  
Shuting Han ◽  
Weijian Yang ◽  
Rafael Yuste
Keyword(s):  
Visual Cortex ◽  
Visual Stimulus ◽  
Sensory Processing ◽  
Calcium Imaging ◽  
Cortical Circuits ◽  
Fundamental Function ◽  
Stimulus Context ◽  
Contextual Modulation ◽  
Two Photon ◽  
Cortical Responses

AbstractCortical processing of sensory events is significantly influenced by context. For instance, a repetitive or redundant visual stimulus elicits attenuated cortical responses, but if the same stimulus is unexpected or “deviant”, responses are augmented. This contextual modulation of sensory processing is likely a fundamental function of neural circuits, yet an understanding of how it is computed is still missing. Using holographic two-photon calcium imaging in awake animals, here we identify three distinct, spatially intermixed ensembles of neurons in mouse primary visual cortex which differentially respond to the same stimulus under separate contexts, including a subnetwork which selectively responds to deviant events. These non-overlapping ensembles are distributed across layers 2-5, though deviance detection is more common in superficial layers. Contextual preferences likely arise locally since they are not present in bottom up inputs from the thalamus or top-down inputs from prefrontal cortex. The functional parcellation of cortical circuits into independent ensembles that encode stimulus context provides a circuit basis underlying cortically based perception of novel or redundant stimuli, a key deficit in many psychiatric disorders.One Sentence SummaryVisual cortex represents deviant and redundant stimuli with separate subnetworks.

scholarly journals Distinct patterns of activity in individual cortical neurons and local networks in primary somatosensory cortex of mice evoked by mechanical limb stimulation

2020 ◽  
Author(s):  
Mischa V. Bandet ◽  
Bin Dong ◽  
Ian R. Winship
Keyword(s):  
Somatosensory Cortex ◽  
Cortical Neurons ◽  
Optical Recording ◽  
Primary Somatosensory Cortex ◽  
Autofluorescence Imaging ◽  
Neuronal Activation ◽  
Local Networks ◽  
Two Photon ◽  
Evoked Activity ◽  
Sensory Evoked

AbstractTo distinguish between somatic stimuli, the primary somatosensory cortex should process dissimilar stimuli with distinct patterns of neuronal activation. Two-photon calcium imaging permits simultaneous optical recording of sensory evoked activity in hundreds of cortical neurons during varied sensory stimulation. Hence, it allows a visualization of patterns of activity in individual neurons and local cortical networks in response to distinct stimulation. Here, flavoprotein autofluorescence imaging was used to map the somatosensory cortex of anaesthetized C57BL/6 mice, and in vivo two-photon Ca2+ imaging was used to define patterns of neuronal activation during mechanical stimulation of the contralateral forelimb or hindlimb at various frequencies (3, 10, 100, 200, and 300 Hz). The data revealed that neurons within the limb associated somatosensory cortex exhibit stimulus-specific patterns of activity. Subsets of neurons were found to have sensory-evoked activity that is either primarily responsive to single stimulus frequencies or broadly responsive to multiple frequencies of limb movement. High frequency stimuli were shown to elicit more activation across the population, with a greater percentage of the population responding and greater percentage of cells with high amplitude responses. Stimulus-evoked cell-cell correlations within these neuronal networks varied as a function of frequency of stimulation, such that each stimulus elicited a distinct pattern that was more consistent across multiple trials of the same stimulus compared to trials at different frequencies of stimulation. The variation in cortical response to these artificial stimuli can thus be represented by the population pattern of supra-threshold Ca2+ transients, the magnitude and temporal properties of the evoked activity, and the structure of the stimulus-evoked correlation between responsive neurons.

scholarly journals Simultaneous Two-Photon Voltage or Calcium Imaging and Multi-Channel Local Field Potential Recordings in Barrel Cortex of Awake and Anesthetized Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Claudia Cecchetto ◽  
Stefano Vassanelli ◽  
Bernd Kuhn
Keyword(s):  
Local Field ◽  
Calcium Imaging ◽  
Local Field Potential ◽  
Barrel Cortex ◽  
Field Potential ◽  
Imaging Data ◽  
Spatiotemporal Resolution ◽  
Two Photon ◽  
Cranial Window ◽  
Sensory Evoked

Neuronal population activity, both spontaneous and sensory-evoked, generates propagating waves in cortex. However, high spatiotemporal-resolution mapping of these waves is difficult as calcium imaging, the work horse of current imaging, does not reveal subthreshold activity. Here, we present a platform combining voltage or calcium two-photon imaging with multi-channel local field potential (LFP) recordings in different layers of the barrel cortex from anesthetized and awake head-restrained mice. A chronic cranial window with access port allows injecting a viral vector expressing GCaMP6f or the voltage-sensitive dye (VSD) ANNINE-6plus, as well as entering the brain with a multi-channel neural probe. We present both average spontaneous activity and average evoked signals in response to multi-whisker air-puff stimulations. Time domain analysis shows the dependence of the evoked responses on the cortical layer and on the state of the animal, here separated into anesthetized, awake but resting, and running. The simultaneous data acquisition allows to compare the average membrane depolarization measured with ANNINE-6plus with the amplitude and shape of the LFP recordings. The calcium imaging data connects these data sets to the large existing database of this important second messenger. Interestingly, in the calcium imaging data, we found a few cells which showed a decrease in calcium concentration in response to vibrissa stimulation in awake mice. This system offers a multimodal technique to study the spatiotemporal dynamics of neuronal signals through a 3D architecture in vivo. It will provide novel insights on sensory coding, closing the gap between electrical and optical recordings.

scholarly journals Neural coding in barrel cortex during whisker-guided locomotion

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Nicholas James Sofroniew ◽  
Yurii A Vlasov ◽  
Samuel Andrew Hires ◽  
Jeremy Freeman ◽  
Karel Svoboda
Keyword(s):  
Calcium Imaging ◽  
Neural Coding ◽  
Closed Loop ◽  
Barrel Cortex ◽  
Relevant Information ◽  
Cortical Circuits ◽  
Tuning Curves ◽  
Stimulus Response ◽  
Two Photon ◽  
Layer 4

Animals seek out relevant information by moving through a dynamic world, but sensory systems are usually studied under highly constrained and passive conditions that may not probe important dimensions of the neural code. Here, we explored neural coding in the barrel cortex of head-fixed mice that tracked walls with their whiskers in tactile virtual reality. Optogenetic manipulations revealed that barrel cortex plays a role in wall-tracking. Closed-loop optogenetic control of layer 4 neurons can substitute for whisker-object contact to guide behavior resembling wall tracking. We measured neural activity using two-photon calcium imaging and extracellular recordings. Neurons were tuned to the distance between the animal snout and the contralateral wall, with monotonic, unimodal, and multimodal tuning curves. This rich representation of object location in the barrel cortex could not be predicted based on simple stimulus-response relationships involving individual whiskers and likely emerges within cortical circuits.

Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo

2011 ◽  
Vol 14 (8) ◽  
pp. 1089-1093 ◽  
Author(s):  
Wolfgang Mittmann ◽  
Damian J Wallace ◽  
Uwe Czubayko ◽  
Jan T Herb ◽  
Andreas T Schaefer ◽  
...  
Keyword(s):  
Calcium Imaging ◽  
Two Photon ◽  
Somatosensory Neurons ◽  
Evoked Activity

scholarly journals Reconciling functional differences in populations of neurons recorded with two-photon imaging and electrophysiology

2020 ◽  
Author(s):  
Joshua H. Siegle ◽  
Peter Ledochowitsch ◽  
Xiaoxuan Jia ◽  
Daniel Millman ◽  
Gabriel K. Ocker ◽  
...  
Keyword(s):  
Calcium Imaging ◽  
Physiological Activity ◽  
Sampling Bias ◽  
Forward Model ◽  
Neural Population ◽  
Evoked Responses ◽  
Two Photon ◽  
Advantages And Disadvantages ◽  
Electrophysiological Recordings ◽  
Sensory Evoked

AbstractExtracellular electrophysiology and two-photon calcium imaging are widely used methods for measuring physiological activity with single-cell resolution across large populations of neurons in the brain. While these two modalities have distinct advantages and disadvantages, neither provides complete, unbiased information about the underlying neural population. Here, we compare evoked responses in visual cortex recorded in awake mice under highly standardized conditions using either imaging or electrophysiology. Across all stimulus conditions tested, we observe a larger fraction of responsive neurons in electrophysiology and higher stimulus selectivity in calcium imaging. This work explores which data transformations are most useful for explaining these modality-specific discrepancies. We show that the higher selectivity in imaging can be partially reconciled by applying a spikes-to-calcium forward model to the electrophysiology data. However, the forward model could not reconcile differences in responsiveness without sub-selecting neurons based on event rate or level of signal contamination. This suggests that differences in responsiveness more likely reflect neuronal sampling bias or cluster-merging artifacts during spike sorting of electrophysiological recordings, rather than flaws in event detection from fluorescence time series. This work establishes the dominant impacts of the two modalities’ respective biases on a set of functional metrics that are fundamental for characterizing sensory-evoked responses.

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