The detection of novel stimuli is critical to learn and survive in a dynamic environment. Though ... more The detection of novel stimuli is critical to learn and survive in a dynamic environment. Though novel stimuli powerfully affect brain activity, their impact on specific cell types and circuits is not well understood. Disinhibition is one candidate mechanism for novelty-induced enhancements in activity. Here we characterize the impact of stimulus novelty on disinhibitory circuit components using longitudinal 2-photon calcium imaging of Vip, Sst, and excitatory populations in the mouse visual cortex. Mice learn a behavioral task with stimuli that become highly familiar, then are tested on both familiar and novel stimuli. Mice consistently perform the task with novel stimuli, yet responses to stimulus presentations and stimulus omissions are dramatically altered. Further, we find that novelty modifies coding of visual as well as behavioral and task information. At the population level, the direction of these changes is consistent with engagement of the Vip-Sst disinhibitory circuit. A...
cortex Laminar dependence of neuronal correlations in visual You might find this additional info ... more cortex Laminar dependence of neuronal correlations in visual You might find this additional info useful...
The brain consists of many cell classes yet in vivo electrophysiology recordings are typically un... more The brain consists of many cell classes yet in vivo electrophysiology recordings are typically unable to identify and monitor their activity in the behaving animal. Here, we employed a systematic approach to link cellular, multi-modal in vitro properties from experiments with in vivo recorded units via computational modeling and optotagging experiments. We found two one-channel and six multi-channel clusters in mouse visual cortex with distinct in vivo properties in terms of activity, cortical depth, and behavior. We used biophysical models to map the two one- and the six multi-channel clusters to specific in vitro classes with unique morphology, excitability and conductance properties that explain their distinct extracellular signatures and functional characteristics. These concepts were tested in ground-truth optotagging experiments with two inhibitory classes unveiling distinct in vivo properties. This multi-modal approach presents a powerful way to separate in vivo clusters and ...
Neuropixels recordings from mouse visual cortex. The dataset was used in the paper: <strong>... more Neuropixels recordings from mouse visual cortex. The dataset was used in the paper: <strong>Multi-regional module-based signal transmission in mouse visual cortex,</strong> Jia et al. (2022) Neuron. For information about experimental procedures, see Siegle, Jia et al. (2021) Nature 592, 86-92 (https://www.nature.com/articles/s41586-020-03171-x). For information about file contents, see https://allensdk.readthedocs.io/en/latest/visual_coding_neuropixels.html The NWB 1.0 files can be opened with HDF5 and HDFview. <strong>Mouse ID</strong> <strong>Genotype</strong> 306046 ['Sst-IRES-Cre/wt;Ai32/wt'] 388523 ['Pvalb-Cre',] 389262 ['Vip-Cre'] 408153 ['Sst-IRES-Cre/wt;Ai32/wt'] 410344 ['Vip-Cre'] 415149 ['wt/wt'] 412809 ['wt/wt'] 412804 ['wt/wt'] 416856 ['Sst-IRES-Cre/wt;Ai32/wt'] 419114 ['wt/wt'] 419117 ['wt/wt'] 419118 ['wt/wt'] 419119 ['wt/wt'] 4244...
The visual cortex is organized hierarchically, but extensive recurrent and parallel pathways make... more The visual cortex is organized hierarchically, but extensive recurrent and parallel pathways make it challenging to decipher signal flow between neuronal populations. Here, we recorded spiking activity from neurons in six interconnected areas along the mouse visual hierarchy. By analyzing leading and lagging spike-timing relationships among all measured neurons, we created a cellular-scale directed graph of the network. Using a novel module-detection algorithm to cluster neurons based on shared connectivity patterns, we uncovered several multi-regional communication modules that are distributed across the visual hierarchy. Based on the direction of signal flow between modules, differences in layer and area distributions, and distinct temporal dynamics, we found these modules support different stages of sensory processing. One module is positioned to transmit feedforward sensory signals along the hierarchy, whereas the other integrates inputs for recurrent processing. These results r...
Cortical circuits can flexibly change with experience and learning, but the effects on specific c... more Cortical circuits can flexibly change with experience and learning, but the effects on specific cell types, including distinct inhibitory types, are not well understood. Here we investigated how excitatory and VIP inhibitory cells in layer 2/3 of mouse visual cortex were impacted by visual experience in the context of a behavioral task. Mice learned a visual change detection task with a set of eight natural scene images. Subsequently, during 2-photon imaging experiments, mice performed the task with these familiar images and three sets of novel images. Strikingly, the temporal dynamics of VIP activity differed markedly between novel and familiar images: VIP cells were stimulus-driven by novel images but were suppressed by familiar stimuli and showed ramping activity when expected stimuli were omitted from a temporally predictable sequence. This prominent change in VIP activity suggests that these cells may adopt different modes of processing under novel versus familiar conditions.
The dimensionality of a network’s collective activity is the number of modes into which it is org... more The dimensionality of a network’s collective activity is the number of modes into which it is organized. This quantity is of great interest in neural coding: small dimensionality suggests a compressed neural code and possibly high robustness and generalizability, while high dimensionality suggests expansion of input features to enable flexible downstream computation. Here, for recurrent neural circuits operating in the ubiquitous balanced regime, we show how dimensionality arises mechanistically via perhaps the most basic property of neural circuits: a single number characterizing the net strength of their connectivity. Our results combine novel theoretical approaches with new analyses of high-density neuropixels recordings and high-throughput synaptic physiology datasets. The analysis of electrophysiological recordings identifies bounds on the dimensionality of neural responses across brain regions, showing that it is on the order of hundreds – striking a balance between high and l...
Extracellular electrophysiology and two-photon calcium imaging are widely used methods for measur... more Extracellular 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 diff...
Temporal continuity of object identity is a natural feature of visual input statistics, and it is... more Temporal continuity of object identity is a natural feature of visual input statistics, and it is potentially exploited -- in an unsupervised manner -- by the ventral visual stream to build and re-shape the neural representation in inferior temporal (IT) cortex and IT-dependent core object recognition behavior. Prior psychophysical studies in humans and electrophysiological studies in monkey IT are individually supportive of this hypothesis. However, due to differences in tasks and experience manipulations, it is not yet known if the reported plasticity of individual IT neurons and the reported human behavioral changes are quantitatively consistent. Here we tested that consistency by building an unsupervised plasticity model that captures the previously-reported IT neural plasticity and combined that model with a previously established IT-to-recognition-behavior linking model. We compared the predictions of the overall model with the results of three new human behavioral experiments...
The mammalian visual system, from retina to neocortex, has been extensively studied at both anato... more The mammalian visual system, from retina to neocortex, has been extensively studied at both anatomical and functional levels. Anatomy indicates the cortico-thalamic system is hierarchical, but characterization of cellular-level functional interactions across multiple levels of this hierarchy is lacking, partially due to the challenge of simultaneously recording activity across numerous regions. Here, we describe a large, open dataset (part of the Allen Brain Observatory) that surveys spiking from units in six cortical and two thalamic regions responding to a battery of visual stimuli. Using spike cross-correlation analysis, we find that inter-area functional connectivity mirrors the anatomical hierarchy from the Allen Mouse Brain Connectivity Atlas. Classical functional measures of hierarchy, including visual response latency, receptive field size, phase-locking to a drifting grating stimulus, and autocorrelation timescale are all correlated with the anatomical hierarchy. Moreover, ...
Cortical circuits are flexible and can change with experience and learning. However, the effects ... more Cortical circuits are flexible and can change with experience and learning. However, the effects of experience on specific cell types including distinct inhibitory types are not well understood. Here we studied how excitatory and VIP inhibitory cells in layer 2/3 of mouse visual cortex were impacted by visual experience in the context of a behavioral task. Mice learned to perform an image change detection task with a set of eight natural scene images. Subsequently, during 2-photon imaging experiments, mice performed the task with these familiar images and three additional sets of novel images. Familiar images evoked less overall activity in both excitatory and VIP populations, and excitatory cells showed higher selectivity for familiar images. The temporal dynamics of VIP cells differed markedly between novel and familiar images: VIP cells were stimulus-driven for novel images but displayed ramping activity during the inter-stimulus interval for familiar images. Moreover, when a fam...
Structural rules underlying functional properties of cortical circuits are poorly understood. To ... more Structural rules underlying functional properties of cortical circuits are poorly understood. To explore these rules systematically, we integrated information from extensive literature curation and large-scale experimental surveys into data-driven, biologically realistic models of the mouse primary visual cortex. The models were constructed at two levels of granularity, using either biophysically-detailed or point-neuron models, with identical network connectivity. Both models were compared to each other and to experimental recordings of neural activity during presentation of visual stimuli to awake mice. Three specific predictions emerge from model construction and simulations: about connectivity between excitatory and parvalbumin-negative inhibitory neurons, functional specialization of connections between excitatory neurons, and the impact of the cortical retinotopic map on structure-function relationships. Finally, despite their vastly different neuronal levels of granularity, b...
Different neuron types serve distinct roles in neural processing. Extracellular electrical record... more Different neuron types serve distinct roles in neural processing. Extracellular electrical recordings are extensively used to study brain function but are typically blind to cell identity. Morpho-electric properties of neurons measured on spatially dense electrode arrays have the potential to distinguish neuron types. Here we used high-density silicon probes to record from cortical and subcortical regions of the mouse brain. Extracellular waveforms of each neuron were detected across many channels and showed distinct spatiotemporal profiles among brain regions. Classification of neurons by brain region was improved with multi-channel compared to single-channel waveforms. In visual cortex, unsupervised clustering identified the canonical regular spiking (RS) and fast spiking (FS) classes, but also indicated a subclass of RS units with unidirectional backpropagating action potentials (BAPs). Moreover, BAPs were observed in many hippocampal RS cells. Overall, waveform analysis of spike...
Gamma components of the local field potential (LFP) are elevated during cognitive and perceptual ... more Gamma components of the local field potential (LFP) are elevated during cognitive and perceptual processes. It has been suggested that gamma power indicates the strength of neuronal population synchrony, which influences the relaying of signals between cortical areas. However, the relationship between coordinated spiking activity and gamma remains unclear, and the influence on corticocortical signaling largely untested. We investigated these issues by recording from neuronal populations in areas V1 and V2 of anesthetized macaque monkeys. We found that visual stimuli that induce a strong, coherent gamma rhythm result in enhanced pairwise and higher-order V1 synchrony. This is associated with stronger coupling of V1-V2 spiking activity, in a retinotopically specific manner. Coupling is more strongly related to the gamma modulation of V1 firing than to the downstream V2 rhythm. Our results thus show that elevated gamma power is associated with stronger coordination of spiking activity ...
The detection of novel stimuli is critical to learn and survive in a dynamic environment. Though ... more The detection of novel stimuli is critical to learn and survive in a dynamic environment. Though novel stimuli powerfully affect brain activity, their impact on specific cell types and circuits is not well understood. Disinhibition is one candidate mechanism for novelty-induced enhancements in activity. Here we characterize the impact of stimulus novelty on disinhibitory circuit components using longitudinal 2-photon calcium imaging of Vip, Sst, and excitatory populations in the mouse visual cortex. Mice learn a behavioral task with stimuli that become highly familiar, then are tested on both familiar and novel stimuli. Mice consistently perform the task with novel stimuli, yet responses to stimulus presentations and stimulus omissions are dramatically altered. Further, we find that novelty modifies coding of visual as well as behavioral and task information. At the population level, the direction of these changes is consistent with engagement of the Vip-Sst disinhibitory circuit. A...
cortex Laminar dependence of neuronal correlations in visual You might find this additional info ... more cortex Laminar dependence of neuronal correlations in visual You might find this additional info useful...
The brain consists of many cell classes yet in vivo electrophysiology recordings are typically un... more The brain consists of many cell classes yet in vivo electrophysiology recordings are typically unable to identify and monitor their activity in the behaving animal. Here, we employed a systematic approach to link cellular, multi-modal in vitro properties from experiments with in vivo recorded units via computational modeling and optotagging experiments. We found two one-channel and six multi-channel clusters in mouse visual cortex with distinct in vivo properties in terms of activity, cortical depth, and behavior. We used biophysical models to map the two one- and the six multi-channel clusters to specific in vitro classes with unique morphology, excitability and conductance properties that explain their distinct extracellular signatures and functional characteristics. These concepts were tested in ground-truth optotagging experiments with two inhibitory classes unveiling distinct in vivo properties. This multi-modal approach presents a powerful way to separate in vivo clusters and ...
Neuropixels recordings from mouse visual cortex. The dataset was used in the paper: <strong>... more Neuropixels recordings from mouse visual cortex. The dataset was used in the paper: <strong>Multi-regional module-based signal transmission in mouse visual cortex,</strong> Jia et al. (2022) Neuron. For information about experimental procedures, see Siegle, Jia et al. (2021) Nature 592, 86-92 (https://www.nature.com/articles/s41586-020-03171-x). For information about file contents, see https://allensdk.readthedocs.io/en/latest/visual_coding_neuropixels.html The NWB 1.0 files can be opened with HDF5 and HDFview. <strong>Mouse ID</strong> <strong>Genotype</strong> 306046 ['Sst-IRES-Cre/wt;Ai32/wt'] 388523 ['Pvalb-Cre',] 389262 ['Vip-Cre'] 408153 ['Sst-IRES-Cre/wt;Ai32/wt'] 410344 ['Vip-Cre'] 415149 ['wt/wt'] 412809 ['wt/wt'] 412804 ['wt/wt'] 416856 ['Sst-IRES-Cre/wt;Ai32/wt'] 419114 ['wt/wt'] 419117 ['wt/wt'] 419118 ['wt/wt'] 419119 ['wt/wt'] 4244...
The visual cortex is organized hierarchically, but extensive recurrent and parallel pathways make... more The visual cortex is organized hierarchically, but extensive recurrent and parallel pathways make it challenging to decipher signal flow between neuronal populations. Here, we recorded spiking activity from neurons in six interconnected areas along the mouse visual hierarchy. By analyzing leading and lagging spike-timing relationships among all measured neurons, we created a cellular-scale directed graph of the network. Using a novel module-detection algorithm to cluster neurons based on shared connectivity patterns, we uncovered several multi-regional communication modules that are distributed across the visual hierarchy. Based on the direction of signal flow between modules, differences in layer and area distributions, and distinct temporal dynamics, we found these modules support different stages of sensory processing. One module is positioned to transmit feedforward sensory signals along the hierarchy, whereas the other integrates inputs for recurrent processing. These results r...
Cortical circuits can flexibly change with experience and learning, but the effects on specific c... more Cortical circuits can flexibly change with experience and learning, but the effects on specific cell types, including distinct inhibitory types, are not well understood. Here we investigated how excitatory and VIP inhibitory cells in layer 2/3 of mouse visual cortex were impacted by visual experience in the context of a behavioral task. Mice learned a visual change detection task with a set of eight natural scene images. Subsequently, during 2-photon imaging experiments, mice performed the task with these familiar images and three sets of novel images. Strikingly, the temporal dynamics of VIP activity differed markedly between novel and familiar images: VIP cells were stimulus-driven by novel images but were suppressed by familiar stimuli and showed ramping activity when expected stimuli were omitted from a temporally predictable sequence. This prominent change in VIP activity suggests that these cells may adopt different modes of processing under novel versus familiar conditions.
The dimensionality of a network’s collective activity is the number of modes into which it is org... more The dimensionality of a network’s collective activity is the number of modes into which it is organized. This quantity is of great interest in neural coding: small dimensionality suggests a compressed neural code and possibly high robustness and generalizability, while high dimensionality suggests expansion of input features to enable flexible downstream computation. Here, for recurrent neural circuits operating in the ubiquitous balanced regime, we show how dimensionality arises mechanistically via perhaps the most basic property of neural circuits: a single number characterizing the net strength of their connectivity. Our results combine novel theoretical approaches with new analyses of high-density neuropixels recordings and high-throughput synaptic physiology datasets. The analysis of electrophysiological recordings identifies bounds on the dimensionality of neural responses across brain regions, showing that it is on the order of hundreds – striking a balance between high and l...
Extracellular electrophysiology and two-photon calcium imaging are widely used methods for measur... more Extracellular 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 diff...
Temporal continuity of object identity is a natural feature of visual input statistics, and it is... more Temporal continuity of object identity is a natural feature of visual input statistics, and it is potentially exploited -- in an unsupervised manner -- by the ventral visual stream to build and re-shape the neural representation in inferior temporal (IT) cortex and IT-dependent core object recognition behavior. Prior psychophysical studies in humans and electrophysiological studies in monkey IT are individually supportive of this hypothesis. However, due to differences in tasks and experience manipulations, it is not yet known if the reported plasticity of individual IT neurons and the reported human behavioral changes are quantitatively consistent. Here we tested that consistency by building an unsupervised plasticity model that captures the previously-reported IT neural plasticity and combined that model with a previously established IT-to-recognition-behavior linking model. We compared the predictions of the overall model with the results of three new human behavioral experiments...
The mammalian visual system, from retina to neocortex, has been extensively studied at both anato... more The mammalian visual system, from retina to neocortex, has been extensively studied at both anatomical and functional levels. Anatomy indicates the cortico-thalamic system is hierarchical, but characterization of cellular-level functional interactions across multiple levels of this hierarchy is lacking, partially due to the challenge of simultaneously recording activity across numerous regions. Here, we describe a large, open dataset (part of the Allen Brain Observatory) that surveys spiking from units in six cortical and two thalamic regions responding to a battery of visual stimuli. Using spike cross-correlation analysis, we find that inter-area functional connectivity mirrors the anatomical hierarchy from the Allen Mouse Brain Connectivity Atlas. Classical functional measures of hierarchy, including visual response latency, receptive field size, phase-locking to a drifting grating stimulus, and autocorrelation timescale are all correlated with the anatomical hierarchy. Moreover, ...
Cortical circuits are flexible and can change with experience and learning. However, the effects ... more Cortical circuits are flexible and can change with experience and learning. However, the effects of experience on specific cell types including distinct inhibitory types are not well understood. Here we studied how excitatory and VIP inhibitory cells in layer 2/3 of mouse visual cortex were impacted by visual experience in the context of a behavioral task. Mice learned to perform an image change detection task with a set of eight natural scene images. Subsequently, during 2-photon imaging experiments, mice performed the task with these familiar images and three additional sets of novel images. Familiar images evoked less overall activity in both excitatory and VIP populations, and excitatory cells showed higher selectivity for familiar images. The temporal dynamics of VIP cells differed markedly between novel and familiar images: VIP cells were stimulus-driven for novel images but displayed ramping activity during the inter-stimulus interval for familiar images. Moreover, when a fam...
Structural rules underlying functional properties of cortical circuits are poorly understood. To ... more Structural rules underlying functional properties of cortical circuits are poorly understood. To explore these rules systematically, we integrated information from extensive literature curation and large-scale experimental surveys into data-driven, biologically realistic models of the mouse primary visual cortex. The models were constructed at two levels of granularity, using either biophysically-detailed or point-neuron models, with identical network connectivity. Both models were compared to each other and to experimental recordings of neural activity during presentation of visual stimuli to awake mice. Three specific predictions emerge from model construction and simulations: about connectivity between excitatory and parvalbumin-negative inhibitory neurons, functional specialization of connections between excitatory neurons, and the impact of the cortical retinotopic map on structure-function relationships. Finally, despite their vastly different neuronal levels of granularity, b...
Different neuron types serve distinct roles in neural processing. Extracellular electrical record... more Different neuron types serve distinct roles in neural processing. Extracellular electrical recordings are extensively used to study brain function but are typically blind to cell identity. Morpho-electric properties of neurons measured on spatially dense electrode arrays have the potential to distinguish neuron types. Here we used high-density silicon probes to record from cortical and subcortical regions of the mouse brain. Extracellular waveforms of each neuron were detected across many channels and showed distinct spatiotemporal profiles among brain regions. Classification of neurons by brain region was improved with multi-channel compared to single-channel waveforms. In visual cortex, unsupervised clustering identified the canonical regular spiking (RS) and fast spiking (FS) classes, but also indicated a subclass of RS units with unidirectional backpropagating action potentials (BAPs). Moreover, BAPs were observed in many hippocampal RS cells. Overall, waveform analysis of spike...
Gamma components of the local field potential (LFP) are elevated during cognitive and perceptual ... more Gamma components of the local field potential (LFP) are elevated during cognitive and perceptual processes. It has been suggested that gamma power indicates the strength of neuronal population synchrony, which influences the relaying of signals between cortical areas. However, the relationship between coordinated spiking activity and gamma remains unclear, and the influence on corticocortical signaling largely untested. We investigated these issues by recording from neuronal populations in areas V1 and V2 of anesthetized macaque monkeys. We found that visual stimuli that induce a strong, coherent gamma rhythm result in enhanced pairwise and higher-order V1 synchrony. This is associated with stronger coupling of V1-V2 spiking activity, in a retinotopically specific manner. Coupling is more strongly related to the gamma modulation of V1 firing than to the downstream V2 rhythm. Our results thus show that elevated gamma power is associated with stronger coordination of spiking activity ...
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