skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


This content will become publicly available on July 8, 2026

Title: Patchy harmonic functional connectivity of the mouse auditory cortex
Analyzing the functional connectivity of the brain is an enormous challenge, as deciphering functional connectivity requires knowledge of functional responses and connections. One promising strategy is analyzing the spatial pattern of activity correlations across cell populations. In the primary auditory cortex (A1), cells respond to different sound features. On the large scale, there exists a tonotopic map, which is fractured at the small scale, raising the question of whether functional connections are spatially ordered or disordered. To test whether functional connectivity on a local and a global scale is also disordered, we first designed a robust statistical model to estimate parameters and test for the significance of the estimated correlation maps. We developed an inference method that allows efficient model fitting and statistical testing to project the correlation maps to 2D space. We then performed in vivo two-photon calcium imaging in layer 2/3 of A1 with pure tones (PT) or a combination of two tones (TT; harmonically related or not). We found that the spatial patterns of signal correlations (SCs) depend on the type of sound stimuli that were presented. The functional 2D maps of PT-driven SCs are more restricted to local neurons than TT signal correlations which showed more global textures. 2D SC patterns for harmonic stimuli showed spatially distinct relationships. TT SCs revealed spatially precise functional connectivity between harmonically related neurons. Thus, even though the frequency preference of neighboring neurons in A1 is functionally diverse, the functional connection pattern of these neurons is functionally precise and harmonically related.  more » « less
Award ID(s):
2032649 2020624
PAR ID:
10656779
Author(s) / Creator(s):
; ; ; ; ; ;
Publisher / Repository:
PNAS
Date Published:
Journal Name:
Proceedings of the National Academy of Sciences
Volume:
122
Issue:
27
ISSN:
0027-8424
Page Range / eLocation ID:
e2510012122
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract Measures of functional connectivity have played a central role in advancing our understanding of how information is transmitted and processed within the brain. Traditionally, these studies have focused on identifying redundant functional connectivity, which involves determining when activity is similar across different sites or neurons. However, recent research has highlighted the importance of also identifying synergistic connectivity—that is, connectivity that gives rise to information not contained in either site or neuron alone. Here, we measured redundant and synergistic functional connectivity between neurons in the mouse primary auditory cortex during a sound discrimination task. Specifically, we measured directed functional connectivity between neurons simultaneously recorded with calcium imaging. We used Granger Causality as a functional connectivity measure. We then used Partial Information Decomposition to quantify the amount of redundant and synergistic information about the presented sound that is carried by functionally connected or functionally unconnected pairs of neurons. We found that functionally connected pairs present proportionally more redundant information and proportionally less synergistic information about sound than unconnected pairs, suggesting that their functional connectivity is primarily redundant. Further, synergy and redundancy coexisted both when mice made correct or incorrect perceptual discriminations. However, redundancy was much higher (both in absolute terms and in proportion to the total information available in neuron pairs) in correct behavioural choices compared to incorrect ones, whereas synergy was higher in absolute terms but lower in relative terms in correct than in incorrect behavioural choices. Moreover, the proportion of redundancy reliably predicted perceptual discriminations, with the proportion of synergy adding no extra predictive power. These results suggest a crucial contribution of redundancy to correct perceptual discriminations, possibly due to the advantage it offers for information propagation, and also suggest a role of synergy in enhancing information level during correct discriminations. 
    more » « less
  2. Abstract Understanding the brain requires understanding neurons’ functional responses to the circuit architecture shaping them. Here we introduce the MICrONS functional connectomics dataset with dense calcium imaging of around 75,000 neurons in primary visual cortex (VISp) and higher visual areas (VISrl, VISal and VISlm) in an awake mouse that is viewing natural and synthetic stimuli. These data are co-registered with an electron microscopy reconstruction containing more than 200,000 cells and 0.5 billion synapses. Proofreading of a subset of neurons yielded reconstructions that include complete dendritic trees as well the local and inter-areal axonal projections that map up to thousands of cell-to-cell connections per neuron. Released as an open-access resource, this dataset includes the tools for data retrieval and analysis1,2. Accompanying studies describe its use for comprehensive characterization of cell types3–6, a synaptic level connectivity diagram of a cortical column4, and uncovering cell-type-specific inhibitory connectivity that can be linked to gene expression data4,7. Functionally, we identify new computational principles of how information is integrated across visual space8, characterize novel types of neuronal invariances9and bring structure and function together to uncover a general principle for connectivity between excitatory neurons within and across areas10,11
    more » « less
  3. Abstract Among approaches aiming toward functional nervous system restoration, those implementing microfabrication techniques allow the manufacture of platforms with distinct geometry where neurons can develop and be guided to form patterned connections in vitro . The interplay between neuronal development and the microenvironment, shaped by the physical limitations, remains largely unknown. Therefore, it is crucial to have an efficient way to quantify neuronal morphological changes induced by physical or contact guidance of the microenvironment. In this study, we first devise and assess a method to prepare anisotropic, gradient poly(dimethylsiloxane) micro-ridge/groove arrays featuring variable local pattern width. We then demonstrate the ability of this single substrate to simultaneously profile the morphologcial and synaptic connectivity changes of primary cultured hippocampal neurons reacting to variable physical conditons, throughout neurodevelopment, in vitro . The gradient microtopography enhanced adhesion within microgrooves, increasing soma density with decreasing pattern width. Decreasing pattern width also reduced dendritic arborization and increased preferential axon growth. Finally, decreasing pattern geometry inhibited presynaptic puncta architecture. Collectively, a method to examine structural development and connectivity in response to physical stimuli is established, and potentially provides insight into microfabricated geometries which promote neural regeneration and repair. 
    more » « less
  4. Abstract Deep continental crustal structures are enigmatic due to lack of direct exposures and limited tools to investigate them remotely. Seismic waves can sample these rocks, but most seismic methods focus on coarse crustal structures while laboratory measurements concentrate on crystal‐scale rock properties, and little work has been conducted to bridge this interpretation gap. In some places, geologic maps of crystalline basement provide samples of the intermediate‐scale fabrics and structures that may represent in situ deep crust. However, previous research has not considered natural geometric variations from map data, nor is this heterogeneity typically included in map‐scale seismic property calculations. Here, we test how map‐scale fabrics influence crustal seismic anisotropy in Colorado by analyzing structural data from geologic maps, combining those data with bulk rock elastic tensors to calculate map‐scale seismic properties, and evaluating the resulting comparisons with observed receiver function A1 (360° periodic) arrivals. Crystalline fabrics, predicted seismic properties, and tectonic structures positively correlate with shallow and deep crustal A1 arrivals. Additionally, widespread correlations occur between mapped fault traces and regional foliations, implying that preexisting mechanical heterogeneity may have strongly influenced subsequent reactivation. We interpret that various mapped geologic contact types (e.g., lithologic and structural) generate A1 arrivals and that multiple parallel features (e.g., faults, foliations, and intrusions) contribute to a seismically visible tectonic grain. Therefore, Colorado's exhumed basement, as expressed in outcrops and maps, offers insight into modern deep crustal geological and geophysical structure. 
    more » « less
  5. Kumar, Arvind (Ed.)
    Characterizing neuronal responses to natural stimuli remains a central goal in sensory neuroscience. In auditory cortical neurons, the stimulus selectivity of elicited spiking activity is summarized by a spectrotemporal receptive field (STRF) that relates neuronal responses to the stimulus spectrogram. Though effective in characterizing primary auditory cortical responses, STRFs of non-primary auditory neurons can be quite intricate, reflecting their mixed selectivity. The complexity of non-primary STRFs hence impedes understanding how acoustic stimulus representations are transformed along the auditory pathway. Here, we focus on the relationship between ferret primary auditory cortex (A1) and a secondary region, dorsal posterior ectosylvian gyrus (PEG). We propose estimating receptive fields in PEG with respect to a well-established high-dimensional computational model of primary-cortical stimulus representations. These “cortical receptive fields” (CortRF) are estimated greedily to identify the salient primary-cortical features modulating spiking responses and in turn related to corresponding spectrotemporal features. Hence, they provide biologically plausible hierarchical decompositions of STRFs in PEG. Such CortRF analysis was applied to PEG neuronal responses to speech and temporally orthogonal ripple combination (TORC) stimuli and, for comparison, to A1 neuronal responses. CortRFs of PEG neurons captured their selectivity to more complex spectrotemporal features than A1 neurons; moreover, CortRF models were more predictive of PEG (but not A1) responses to speech. Our results thus suggest that secondary-cortical stimulus representations can be computed as sparse combinations of primary-cortical features that facilitate encoding natural stimuli. Thus, by adding the primary-cortical representation, we can account for PEG single-unit responses to natural sounds better than bypassing it and considering as input the auditory spectrogram. These results confirm with explicit details the presumed hierarchical organization of the auditory cortex. 
    more » « less