A layer-specific model of cortical sensory aging
Poster No:
1137
Submission Type:
Abstract Submission
Authors:
Peng Liu1, Juliane Doehler2, Julia Henschke2, Alicia Northall3, Angela Serian4, D. Samuel Schwarzkopf5, Oliver Speck6, Janelle Pakan2, Esther Kühn7
Institutions:
1Hertie Institute for Clinical Brain Research (HIH)), Tübingen, Germany, 2Institute for Cognitive Neurology and Dementia Research (IKND), Magdeburg, Germany, 3Nuffield Department of Clinical Neurosciences, Oxford, United Kingdom, 4Institute of Cognitive and Clinical Neuroscience (IKND), Heidelberg, Germany, 5University of Auckland, Auckland, Auckland, 6German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany, 7Hertie Institute for Clinical Brain Research (HIH), Tübingen, Baden-Württemberg
First Author:
Co-Author(s):
Introduction:
Sensory processing is organized in a layered architecture with segregated input, output and modulatory circuits. This layered architecture of sensory systems is a convergent feature in animal evolution (Stacho et al., 2020). A comprehensive understanding of (dys)functional sensory systems requires a detailed understanding of alterations in the layer-specific architecture and the associated phenotypes. This is so far lacking, not only for sensory systems but for cortical dysfunction in general.
Sensory dysfunction comes with different cortical phenotypes, including increases in receptive field (RF) sizes (Liu et al., 2021), functional overactivation, decreases in lateral inhibition (Pleger et al., 2016) and structural alterations such as cortical thinning (Calì et al., 2018). However, it is unclear how changes in the layer architecture may contribute to the alterations characterizing sensory cortices with reduced functionality.
Sensory dysfunction comes with different cortical phenotypes, including increases in receptive field (RF) sizes (Liu et al., 2021), functional overactivation, decreases in lateral inhibition (Pleger et al., 2016) and structural alterations such as cortical thinning (Calì et al., 2018). However, it is unclear how changes in the layer architecture may contribute to the alterations characterizing sensory cortices with reduced functionality.
Methods:
Here, we employed a unique approach to target this question by combining layer-specific structural and layer-specific functional 7T-MRI of primary somatosensory cortex (SI) with behavioral assessments from two cohorts of healthy younger and older adults. Cortical aging serves as a suitable model system to investigate the layer-specific architecture of sensory dysfunction as structural and functional reorganization is observed at different levels of the processing hierarchy, and affects behavior (Popescu et al., 2021). To better understand the mechanistic underpinnings of the observed changes, we used in vivo 2-photon calcium imaging (2PCI) in younger and older mice to investigate neuronal response differences at different cortical depths (Chen et al., 2013). We also used post mortem histological examination on mice as it provides deeper insights into layer-specific structural changes.
Results:
Our study presents four major results that we used to develop a novel layer model of sensory aging (see Fig. 1): (1) Increased sensory input channel: In older adults, in spite of overall cortical thinning, the middle layer (i.e., input layer IV, identified using a previously published approach, Doehler et al. 2023) presents with increased thickness, higher myelin content, and a more pronounced antagonistic center-surround relationship between signals and cortical depth. An adult with congenital arm loss shows, on the other hand, a shrinkage specifically of layer IV of SI. This speaks towards a plasticity-mediated mechanism of layer IV thickness modulation in humans. (2) Cortical thinning driven by deep layer thinning: Reduced cortical thickness in older compared with younger adults is not homogenous across layers but driven by deep layer thinning. (3) Preserved low-myelin hand-face border in layer IV: Low-myelin borders in input layer IV are preserved older compared to younger adults as well as in an individual with congenital arm loss. (4) Altered modulation channel: Older adults show less thickness but more myelin in deep layers, which is mirrored by overall cell loss and increased PV+ cell density in older mice. This is accompanied by no alterations or even an increase in inhibitory interactions in older adults and mice, making PV-cell driven inhibition a likely underlying mechanism.
Conclusions:
Taken together, the novel layer model of aging provides key and novel information on SI organization and aging sensory circuits that may explain cortical dysfunction in health and disease, which is of particular importance for developing intervention to preserve sensory functions in aging and neurodegeneration in the future. This work also provides impactful relevance for understanding the neuronal mechanisms that underlie topographic organization and plasticity in general by transferring mechanistic insights from animal to human research. Given the layer-specific profile was different from primary motor cortex, our data also motivate the detailed assessment of layer-specific circuits in different cortical areas.
Lifespan Development:
Aging 1
Modeling and Analysis Methods:
Bayesian Modeling
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Cortical Cyto- and Myeloarchitecture
Novel Imaging Acquisition Methods:
BOLD fMRI
Perception, Attention and Motor Behavior:
Perception: Tactile/Somatosensory 2
Keywords:
Aging
Cortical Layers
FUNCTIONAL MRI
HIGH FIELD MR
Myelin
Plasticity
Somatosensory
STRUCTURAL MRI
Other - receptive field, overactivation
1|2Indicates the priority used for review
Provide references using author date format
Chen, T.-W., Wardill, T. J., Sun, Y., Pulver, S. R., Renninger, S. L., Baohan, A., Schreiter, E. R., Kerr, R. A., Orger, M. B., Jayaraman, V., Looger, L. L., Svoboda, K., & Kim, D. S. (2013). Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature, 499(7458), 295–300. https://doi.org/10.1038/nature12354
Doehler, J., Northall, A., Liu, P., Fracasso, A., Chrysidou, A., Speck, O., Lohmann, G., Wolbers, T., & Kuehn, E. (2023). The 3D Structural Architecture of the Human Hand Area is Non-Topographic. The Journal of Neuroscience, JN-RM-1692-22. https://doi.org/10.1523/JNEUROSCI.1692-22.2023
Liu, P., Chrysidou, A., Doehler, J., Hebart, M. N., Wolbers, T., & Kuehn, E. (2021). The organizational principles of de-differentiated topographic maps in somatosensory cortex. eLife, 10, e60090. https://doi.org/10.7554/eLife.60090
Pleger, B., Wilimzig, C., Nicolas, V., Kalisch, T., Ragert, P., Tegenthoff, M., & Dinse, H. R. (2016). A complementary role of intracortical inhibition in age-related tactile degradation and its remodelling in humans. Scientific Reports, 6(1), Article 1. https://doi.org/10.1038/srep27388
Popescu, I. R., Le, K. Q., Ducote, A. L., Li, J. E., Leland, A. E., & Mostany, R. (2021). Increased intrinsic excitability and decreased synaptic inhibition in aged somatosensory cortex pyramidal neurons. Neurobiology of Aging, 98, 88–98. https://doi.org/10.1016/j.neurobiolaging.2020.10.007
Stacho, M., Herold, C., Rook, N., Wagner, H., Axer, M., Amunts, K., & Güntürkün, O. (2020). A cortex-like canonical circuit in the avian forebrain. Science, 369(6511), eabc5534. https://doi.org/10.1126/science.abc5534