scholarly journals Conditioning sharpens the spatial representation of rewarded stimuli in mouse primary visual cortex

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Pieter M Goltstein ◽  
Guido T Meijer ◽  
Cyriel MA Pennartz
Keyword(s):  
Visual Space ◽  
Spatial Separation ◽  
Time Lapse ◽  
Optical Signal ◽  
Population Coding ◽  
Cortical Representation ◽  
Population Activity ◽  
Two Photon ◽  
Structure Of Population

Reward is often employed as reinforcement in behavioral paradigms but it is unclear how the visuospatial aspect of a stimulus-reward association affects the cortical representation of visual space. Using a head-fixed paradigm, we conditioned mice to associate the same visual pattern in adjacent retinotopic regions with availability and absence of reward. Time-lapse intrinsic optical signal imaging under anesthesia showed that conditioning increased the spatial separation of mesoscale cortical representations of reward predicting- and non-reward predicting stimuli. Subsequent in vivo two-photon calcium imaging revealed that this improved separation correlated with enhanced population coding for retinotopic location, specifically for the trained orientation and spatially confined to the V1 region where rewarded and non-rewarded stimulus representations bordered. These results are corroborated by conditioning-induced differences in the correlation structure of population activity. Thus, the cortical representation of visual space is sharpened as consequence of associative stimulus-reward learning while the overall retinotopic map remains unaltered.

scholarly journals Dual-color volumetric imaging of neural activity of cortical columns

2018 ◽  
Author(s):  
Shuting Han ◽  
Weijian Yang ◽  
Rafael Yuste
Keyword(s):  
Neural Activity ◽  
High Speed ◽  
Neural Circuits ◽  
Emergent Properties ◽  
Spatiotemporal Resolution ◽  
Population Activity ◽  
Volumetric Imaging ◽  
Two Photon ◽  
Dual Color

To capture the emergent properties of neural circuits, high-speed volumetric imaging of neural activity at cellular resolution is desirable. But while conventional two-photon calcium imaging is a powerful tool to study population activity in vivo, it is restrained to two-dimensional planes. Expanding it to 3D while maintaining high spatiotemporal resolution appears necessary. Here, we developed a two-photon microscope with dual-color laser excitation that can image neural activity in a 3D volume. We imaged the neuronal activity of primary visual cortex from awake mice, spanning from L2 to L5 with 10 planes, at a rate of 10 vol/sec, and demonstrated volumetric imaging of L1 long-range PFC projections and L2/3 somatas. Using this method, we map visually-evoked neuronal ensembles in 3D, finding a lack of columnar structure in orientation responses and revealing functional correlations between cortical layers which differ from trial to trial and are missed in sequential imaging. We also reveal functional interactions between presynaptic L1 axons and postsynaptic L2/3 neurons. Volumetric two-photon imaging appears an ideal method for functional connectomics of neural circuits.

scholarly journals Emergent cortical circuit dynamics contain dense, interwoven ensembles of spike sequences

2017 ◽  
Vol 118 (3) ◽  
pp. 1914-1925 ◽  
Author(s):  
Joseph B. Dechery ◽  
Jason N. MacLean
Keyword(s):  
Ex Vivo ◽  
Temporal Coding ◽  
Population Activity ◽  
Flexible Assembly ◽  
Two Photon ◽  
Phase Sequence ◽  
Spike Sequences ◽  
Neuronal Assembly ◽  
Large Repertoire

Temporal codes are theoretically powerful encoding schemes, but their precise form in the neocortex remains unknown in part because of the large number of possible codes and the difficulty in disambiguating informative spikes from statistical noise. A biologically plausible and computationally powerful temporal coding scheme is the Hebbian assembly phase sequence (APS), which predicts reliable propagation of spikes between functionally related assemblies of neurons. Here, we sought to measure the inherent capacity of neocortical networks to produce reliable sequences of spikes, as would be predicted by an APS code. To record microcircuit activity, the scale at which computation is implemented, we used two-photon calcium imaging to densely sample spontaneous activity in murine neocortical networks ex vivo. We show that the population spike histogram is sufficient to produce a spatiotemporal progression of activity across the population. To more comprehensively evaluate the capacity for sequential spiking that cannot be explained by the overall population spiking, we identify statistically significant spike sequences. We found a large repertoire of sequence spikes that collectively comprise the majority of spiking in the circuit. Sequences manifest probabilistically and share neuron membership, resulting in unique ensembles of interwoven sequences characterizing individual spatiotemporal progressions of activity. Distillation of population dynamics into its constituent sequences provides a way to capture trial-to-trial variability and may prove to be a powerful decoding substrate in vivo. Informed by these data, we suggest that the Hebbian APS be reformulated as interwoven sequences with flexible assembly membership due to shared overlapping neurons. NEW & NOTEWORTHY Neocortical computation occurs largely within microcircuits comprised of individual neurons and their connections within small volumes (<500 μm3). We found evidence for a long-postulated temporal code, the Hebbian assembly phase sequence, by identifying repeated and co-occurring sequences of spikes. Variance in population activity across trials was explained in part by the ensemble of active sequences. The presence of interwoven sequences suggests that neuronal assembly structure can be variable and is determined by previous activity.

scholarly journals Phospholipid Composition of APOE Lipoproteins Affects Microglia Activation in an Isoform-specific Manner

2020 ◽  
Author(s):  
Nicholas Fitz ◽  
KyongNyon Nam ◽  
Cody Wolfe ◽  
Florent Letronne ◽  
Brittany Playso ◽  
...  
Keyword(s):  
Phospholipid Composition ◽  
Time Lapse ◽  
Postmortem Brain ◽  
Two Photon ◽  
Activated State ◽  
Microglial Migration ◽  
Human Apoe3 ◽  
High Level ◽  
Microglial Response

Abstract Apolipoprotein E4 (APOE) is the strongest genetic risk factor for Alzheimer’s disease (AD). Our lipidomic analysis identified a common phospholipid signature with a high level of correlation between APOEε3/3 and APOEε4/4 AD postmortem brain samples and native lipoproteins isolated from astrocyte conditioned media of mice expressing human APOE3 or APOE4. Behavioral testing demonstrated that native E3 lipoproteins were more effective than E4 at ameliorating the harmful effects of Aβ on cognition. We posit that APOE isoform-specific differences in the phospholipid composition of native lipoproteins prompt a differential microglial response. Using time-lapse in vivo two-photon imaging we compared the effect of E3 or E4 infused with Aβ and determined that E3 lipoproteins induced a faster microglial migration towards Aβ. To determine how E3 and E4 lipoproteins affect microglial transcriptome in response to Aβ we performed bulk and single cell RNA-seq of WT and Trem2ko mice. We show that compared to E4, cortical infusion of E3 lipoproteins upregulated a higher proportion of genes associated with an activated immune response accompanied by a downregulation of homeostatic genes. scRNA-seq identified microglia-specific clusters affected by Trem2 deficiency suggesting that lack of Trem2 impairs the transition of microglia from homeostatic to an activated state. Compared to E3, E4-expressing microglia showed a reduced Aβ uptake that was additionally aggravated by Trem2 deficiency. Together, our findings have elucidated unique phenotypic and transcriptional differences in the microglial response to Aβ in the presence of E3 or E4 lipoproteins which could impact AD pathogenesis.

scholarly journals Uniform spatial spread of population activity in primate parafoveal V1

2012 ◽  
Vol 107 (7) ◽  
pp. 1857-1867 ◽  
Author(s):  
Chris R. Palmer ◽  
Yuzhi Chen ◽  
Eyal Seidemann
Keyword(s):  
Single Point ◽  
Fundamental Property ◽  
Visual Space ◽  
Population Coding ◽  
Population Activity ◽  
Spatial Spread ◽  
Complete Representation ◽  
V1 Neurons ◽  
Point Image ◽  
Cortical Point

What are the shape and size of the region in primate V1 that processes information from a single point in visual space? This region, a fundamental property termed cortical point image (CPI) ( McIlwain 1986 ), represents the minimal population of V1 neurons that can be activated by a visual stimulus and therefore has important implications for population coding in the cortex. Previous indirect attempts to measure the CPI in macaque V1 using sparse microelectrode recordings resulted in conflicting findings. Whereas some early studies suggested that CPI size is constant throughout V1 (e.g., Hubel and Wiesel 1974 ), others have reported large changes in CPI size in parafoveal V1 (e.g., Van Essen et al. 1984 ). To resolve this controversy, we used voltage-sensitive dye imaging in V1 of fixating monkeys to directly measure the subthreshold CPI and several related properties across a range of parafoveal eccentricities. We found that despite large changes in other properties of the retinotopic map, the subthreshold CPI is approximately constant and extends over ∼6 × 8 mm2. This large and invariant CPI ensures a uniform representation of each point in visual space, with a complete representation of all visual features in V1, as originally proposed by Hubel and Wiesel (1974) . In addition, we found several novel and unexpected asymmetries and anisotropies in the shapes of the CPI and the population receptive field. These results expand our understanding of the representation of visual space in V1 and are likely to be relevant for the representations of stimuli in other sensory cortical areas.

scholarly journals Protocadherin-19 and N-cadherin interact to control cell movements during anterior neurulation

2010 ◽  
Vol 191 (5) ◽  
pp. 1029-1041 ◽  
Author(s):  
Sayantanee Biswas ◽  
Michelle R. Emond ◽  
James D. Jontes
Keyword(s):  
Cell Adhesion ◽  
Control Cell ◽  
Time Lapse ◽  
Image Sequences ◽  
Cell Movements ◽  
Calcium Dependent ◽  
Two Photon ◽  
Cadherin Superfamily

The protocadherins comprise the largest subgroup within the cadherin superfamily, yet their cellular and developmental functions are not well understood. In this study, we demonstrate that pcdh19 (protocadherin 19) acts synergistically with n-cadherin (ncad) during anterior neurulation in zebrafish. In addition, Pcdh19 and Ncad interact directly, forming a protein–protein complex both in vitro and in vivo. Although both molecules are required for calcium-dependent adhesion in a zebrafish cell line, the extracellular domain of Pcdh19 does not exhibit adhesive activity, suggesting that the involvement of Pcdh19 in cell adhesion is indirect. Quantitative analysis of in vivo two-photon time-lapse image sequences reveals that loss of either pcdh19 or ncad impairs cell movements during neurulation, disrupting both the directedness of cell movements and the coherence of movements among neighboring cells. Our results suggest that Pcdh19 and Ncad function together to regulate cell adhesion and to mediate morphogenetic movements during brain development.

scholarly journals Active Learning of Cortical Connectivity from Two-Photon Imaging Data

2018 ◽  
Author(s):  
Martín Bertrán ◽  
Natalia Martínez ◽  
Ye Wang ◽  
David Dunson ◽  
Guillermo Sapiro ◽  
...  
Keyword(s):  
Active Learning ◽  
Small World ◽  
Real Data ◽  
Sensory Stimulation ◽  
Imaging Data ◽  
Population Activity ◽  
Two Photon ◽  
Photon Imaging ◽  
Two Photon Imaging

AbstractUnderstanding how groups of neurons interact within a network is a fundamental question in system neuroscience. Instead of passively observing the ongoing activity of a network, we can typically perturb its activity, either by external sensory stimulation or directly via techniques such as two-photon optogenetics. A natural question is how to use such perturbations to identify the connectivity of the network efficiently. Here we introduce a method to infer sparse connectivity graphs from in-vivo, two-photon imaging of population activity in response to external stimuli. A novel aspect of the work is the introduction of a recommended distribution, incrementally learned from the data, to optimally refine the inferred network.. Unlike existing system identification techniques, this “active learning” method automatically focuses its attention on key undiscovered areas of the network, instead of targeting global uncertainty indicators like parameter variance. We show how active learning leads to faster inference while, at the same time, provides confidence intervals for the network parameters. We present simulations on artificial small-world networks to validate the methods and apply the method to real data. Analysis of frequency of motifs recovered show that cortical networks are consistent with a small-world topology model.

scholarly journals Oxysterols and EBI2 promote osteoclast precursor migration to bone surfaces and regulate bone mass homeostasis

2015 ◽  
Vol 212 (11) ◽  
pp. 1931-1946 ◽  
Author(s):  
Erin Nevius ◽  
Flavia Pinho ◽  
Meera Dhodapkar ◽  
Huiyan Jin ◽  
Kristina Nadrah ◽  
...  
Keyword(s):  
Bone Mass ◽  
Therapeutic Potential ◽  
Time Lapse ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
Time Lapse Microscopy ◽  
Necessary And Sufficient ◽  
Gαi Protein

Bone surfaces attract hematopoietic and nonhematopoietic cells, such as osteoclasts (OCs) and osteoblasts (OBs), and are targeted by bone metastatic cancers. However, the mechanisms guiding cells toward bone surfaces are essentially unknown. Here, we show that the Gαi protein–coupled receptor (GPCR) EBI2 is expressed in mouse monocyte/OC precursors (OCPs) and its oxysterol ligand 7α,25-dihydroxycholesterol (7α,25-OHC) is secreted abundantly by OBs. Using in vitro time-lapse microscopy and intravital two-photon microscopy, we show that EBI2 enhances the development of large OCs by promoting OCP motility, thus facilitating cell–cell interactions and fusion in vitro and in vivo. EBI2 is also necessary and sufficient for guiding OCPs toward bone surfaces. Interestingly, OCPs also secrete 7α,25-OHC, which promotes autocrine EBI2 signaling and reduces OCP migration toward bone surfaces in vivo. Defective EBI2 signaling led to increased bone mass in male mice and protected female mice from age- and estrogen deficiency–induced osteoporosis. This study identifies a novel pathway involved in OCP homing to the bone surface that may have significant therapeutic potential.

CMT disease 2A and demyelination decouple ATP and ROS production by axonal mitochondria

2018 ◽  
Author(s):  
Gerben van Hameren ◽  
Graham Campbell ◽  
Marie Deck ◽  
Jade Berthelot ◽  
Roman Chrast ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Time Lapse ◽  
Ros Production ◽  
Oxygen Species ◽  
Myelinated Axons ◽  
Charcot Marie Tooth ◽  
Atp Production ◽  
Two Photon ◽  
Demyelinating Peripheral Neuropathy

AbstractMitochondria are critical for the function and maintenance of myelinated axons notably through ATP production. A by-product of this activity is reactive oxygen species (ROS), which are highly deleterious for neurons. While ROS and metabolism are involved in several neurodegenerative diseases, it is still unclear how axonal activity or myelin modulates ATP and ROS production in axonal mitochondria. We imaged and quantified mitochondrial ATP and hydrogen peroxide (H2O2) in resting or stimulated peripheral nerve myelinated axons in vivo, using genetically-encoded fluorescent probes, two-photon time-lapse and CARS imaging. ATP and H2O2 productions are intrinsically higher in nodes of Ranvier even in resting conditions. Axonal firing increased both ATP and H2O2 productions but with different dynamics. In neuropathic MFN2R94Q mice, mimicking Charcot-Marie-Tooth 2A disease, defective mitochondria failed to upregulate ATP production following axonal activity. However, H2O2 production was dramatically sustained. Mimicking demyelinating peripheral neuropathy resulted in a reduced production of ATP while H2O2 level soared. Taken together, our results suggest that ATP and ROS productions are decoupled under neuropathic conditions, which may compromise axonal function and integrity.

The role of the dentate gyrus in mnemonic functions

Neuroforum ◽  
2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Jonas-Frederic Sauer ◽  
Marlene Bartos
Keyword(s):  
Dentate Gyrus ◽  
Memory Formation ◽  
Population Activity ◽  
Two Photon ◽  
Select Group ◽  
Cell Association ◽  
Mechanisms Of Memory ◽  
Input Gate

AbstractThe hippocampus is decisive for the storage of conscious memories. Current theories suggest that experience-dependent modifications in excitation–inhibition balance enable a select group of neurons to form a new cell association during learning which represents the new memory trace. It was further proposed that particularly GABAergic-inhibitory interneurons have a large impact on population activity in neuronal networks by means of their inhibitory output synapses. They synchronize active principal cells at high frequencies, thereby supporting their binding to cell assemblies to jointly encode information. However, how cell associations emerge in space and time and how interneurons may contribute to this process is still largely unknown. We started to address this fundamental question in the dentate gyrus (DG) as the input gate of the hippocampus, which has an indispensable role in conscious memory formation. We used a combination of in vivo chronic two-photon imaging of population activity in the DG and the hippocampal areas CA1–3 of mice exposed to a virtual reality, in which they perform a goal-oriented spatial memory tasks, with high-density in vivo recordings and multiple whole-cell recordings in acute slice preparations, to determine how memory engrams emerge during learning. We further examine how GABAergic interneurons may contribute to this process. We believe that these lines of research will add to a better understanding on the mechanisms of memory formation in cortical networks.

scholarly journals Distinct neural dynamics underlie the encoding of visual speed in stationary and running mice

2021 ◽  
Author(s):  
Edward A B Horrocks ◽  
Aman B Saleem
Keyword(s):  
Single Neuron ◽  
Dynamic Range ◽  
Temporal Dynamics ◽  
Population Coding ◽  
Neural Responses ◽  
Population Activity ◽  
Visual Inputs ◽  
Structure Of Population ◽  
Time Courses ◽  
Visual Speed

Sensory experiences are often driven by an animal's self-motion and locomotion is known to modulate neural responses in the mouse visual system. This modulation is hypothesised to improve the processing of behaviourally relevant visual inputs, which may change rapidly during locomotion. However, little is known about how locomotion modulates the temporal dynamics (time courses) of visually-evoked neural responses. Here, we analysed the temporal dynamics of single neuron and population responses to dot field stimuli moving at a range of visual speeds using the Visual Coding dataset from the Allen Institute for Brain Science (Siegle et al, 2021). Single neuron responses had diverse temporal dynamics that varied between stationary and running sessions. Increased dynamic range and more reliable responses in running sessions enabled faster, stronger and more persistent encoding of visual speed. Population activity reflected the temporal dynamics of single neuron responses, including their modulation by locomotor state - neural trajectories of population activity made more direct transitions between baseline and stimulus steady states in running sessions. The structure of population coding also changed with locomotor state - population activity prioritised the encoding of visual speed in running, but not stationary sessions. Our results reveal a profound influence of locomotion on the temporal dynamics of neural responses. We demonstrate that during locomotion, mouse visual areas prioritise the encoding of potentially fast-changing, behaviourally relevant visual features.

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