Search

Recent long-term measurements of neuronal activity have revealed that, despite stability in large-scale topographic maps, the tuning properties of individual cortical neurons can undergo substantial reformatting over days. To shed light on this apparent contradiction, we captured the sound response dynamics of auditory cortical neurons using repeated 2-photon calcium imaging in awake mice. We measured sound-evoked responses to a set of pure tone and complex sound stimuli in more than 20,000 auditory cortex neurons over several days. We found that a substantial fraction of neurons dropped in and out of the population response. We modeled these dynamics as a simple discrete-time Markov chain, capturing the continuous changes in responsiveness observed during stable behavioral and environmental conditions. Although only a minority of neurons were driven by the sound stimuli at a given time point, the model predicts that most cells would at least transiently become responsive within 100 days. We observe that, despite single-neuron volatility, the population-level representation of sound frequency was stably maintained, demonstrating the dynamic equilibrium underlying the tonotopic map. Our results show that sensory maps are maintained by shifting subpopulations of neurons "sharing" the job of creating a sensory representation., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Salience is a broad and widely used concept in neuroscience whose neuronal correlates, however, remain elusive. In behavioral conditioning, salience is used to explain various effects, such as stimulus overshadowing, and refers to how fast and strongly a stimulus can be associated with a conditioned event. Here, we identify sounds of equal intensity and perceptual detectability, which due to their spectro-temporal content recruit different levels of population activity in mouse auditory cortex. When using these sounds as cues in a Go/NoGo discrimination task, the degree of cortical recruitment matches the salience parameter of a reinforcement learning model used to analyze learning speed. We test an essential prediction of this model by training mice to discriminate light-sculpted optogenetic activity patterns in auditory cortex, and verify that cortical recruitment causally determines association or overshadowing of the stimulus components. This demonstrates that cortical recruitment underlies major aspects of stimulus salience during reinforcement learning.

Dynamic remodeling of connectivity is a fundamental feature of neocortical circuits. Unraveling the principles underlying these dynamics is essential for the understanding of how neuronal circuits give rise to computations. Moreover, as complete descriptions of the wiring diagram in cortical tissues are becoming available, deciphering the dynamic elements in these diagrams is crucial for relating them to cortical function. Here, we used chronic in vivo two-photon imaging to longitudinally follow a few thousand dendritic spines in the mouse auditory cortex to study the determinants of these spines' lifetimes. We applied nonlinear regression to quantify the independent contribution of spine age and several morphological parameters to the prediction of the future survival of a spine. We show that spine age, size, and geometry are parameters that can provide independent contributions to the prediction of the longevity of a synaptic connection. In addition, we use this framework to emulate a serial sectioning electron microscopy experiment and demonstrate how incorporation of morphological information of dendritic spines from a single time-point allows estimation of future connectivity states. The distinction between predictable and nonpredictable connectivity changes may be used in the future to identify the specific adaptations of neuronal circuits to environmental changes. The full dataset is publicly available for further analysis. Significance statement: The neural architecture in the neocortex exhibits constant remodeling. The functional consequences of these modifications are poorly understood, in particular because the determinants of these changes are largely unknown. Here, we aimed to identify those modifications that are predictable from current network state. To that goal, we repeatedly imaged thousands of dendritic spines in the auditory cortex of mice to assess the morphology and lifetimes of synaptic connections. We developed models based on morphological features of dendritic spines that allow predicting future turnover of synaptic connections. The dynamic models presented in this paper provide a quantitative framework for adding putative temporal dynamics to the static description of a neuronal circuit from single time-point connectomics experiments., (Copyright © 2015 the authors 0270-6474/15/3512535-10$15.00/0.)

Sensory cortices are commonly structured topographically; however, the extent to which this organization principle is preserved at the microcircuit level is debated. In this issue of Neuron, Issa et al. (2014) revisit this question by combining calcium imaging in awake mice at large scales encompassing the whole auditory cortex and small scales providing single-cell resolution., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Long-lasting changes in synaptic connections induced by relevant experiences are believed to represent the physical correlate of memories. Here, we combined chronic in vivo two-photon imaging of dendritic spines with auditory-cued classical conditioning to test if the formation of a fear memory is associated with structural changes of synapses in the mouse auditory cortex. We find that paired conditioning and unpaired conditioning induce a transient increase in spine formation or spine elimination, respectively. A fraction of spines formed during paired conditioning persists and leaves a long-lasting trace in the network. Memory recall triggered by the reexposure of mice to the sound cue did not lead to changes in spine dynamics. Our findings provide a synaptic mechanism for plasticity in sound responses of auditory cortex neurons induced by auditory-cued fear conditioning; they also show that retrieval of an auditory fear memory does not lead to a recapitulation of structural plasticity in the auditory cortex as observed during initial memory consolidation.

The ability to group stimuli into perceptual categories is essential for efficient interaction with the environment. Discrete dynamics that emerge in brain networks are believed to be the neuronal correlate of category formation. Observations of such dynamics have recently been made; however, it is still unresolved if they actually match perceptual categories. Using in vivo two-photon calcium imaging in the auditory cortex of mice, we show that local network activity evoked by sounds is constrained to few response modes. Transitions between response modes are characterized by an abrupt switch, indicating attractor-like, discrete dynamics. Moreover, we show that local cortical responses quantitatively predict discrimination performance and spontaneous categorization of sounds in behaving mice. Our results therefore demonstrate that local nonlinear dynamics in the auditory cortex generate spontaneous sound categories which can be selected for behavioral or perceptual decisions., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Long-lasting changes in synaptic connections induced by relevant experiences are believed to represent the physical correlate of memories. Here, we combined chronic in vivo two-photon imaging of dendritic spines with auditory-cued classical conditioning to test if the formation of a fear memory is associated with structural changes of synapses in the mouse auditory cortex. We find that paired conditioning and unpaired conditioning induce a transient increase in spine formation or spine elimination, respectively. A fraction of spines formed during paired conditioning persists and leaves a long-lasting trace in the network. Memory recall triggered by the reexposure of mice to the sound cue did not lead to changes in spine dynamics. Our findings provide a synaptic mechanism for plasticity in sound responses of auditory cortex neurons induced by auditory-cued fear conditioning; they also show that retrieval of an auditory fear memory does not lead to a recapitulation of structural plasticity in the auditory cortex as observed during initial memory consolidation. [ABSTRACT FROM AUTHOR]

Sensory stimuli have long been thought to be represented in the brain as activity patterns of specific neuronal assemblies. However, we still know relatively little about the long-term dynamics of sensory representations. Using chronic in vivo calcium imaging in the mouse auditory cortex, we find that sensory representations undergo continuous recombination, even under behaviorally stable conditions. Auditory cued fear conditioning introduces a bias into these ongoing dynamics, resulting in a long-lasting increase in the number of stimuli activating the same subset of neurons. This plasticity is specific for stimuli sharing representational similarity to the conditioned sound prior to conditioning and predicts behaviorally observed stimulus generalization. Our findings demonstrate that learning-induced plasticity leading to a representational linkage between the conditioned stimulus and non-conditioned stimuli weaves into ongoing dynamics of the brain rather than acting on an otherwise static substrate. [Display omitted] • Chronic in vivo two-photon calcium imaging of >36k neurons in mouse auditory cortex • Drift of auditory representations despite stable environmental conditions • Increased co-activation of neurons by CS+ and nonCS+ sounds after conditioning • Degree of co-activation is predictive of behavioral generalization Using longitudinal calcium imaging of sound-evoked activity patterns in the mouse auditory cortex, Aschauer et al. observe increased formation of associations between sound representations following auditory-cued fear conditioning. The degree of newly formed associations predicted behavioral generalization between conditioned and non-conditioned sounds. [ABSTRACT FROM AUTHOR]