Associate Professor in Molecular and Integrative Physiology
Benjamin R. and Elinor W. Bullock and Edwin E. and Jeanne Bullock Goldberg Professorial Scholar
Computational Biology, Imaging, Neurobiology, Optogenetics, Sensory Processing
Disease Research Interests
Aging Related Diseases, Neurological and Behavioral Disorders
The role of top-down projections in the processing of complex sounds
Our laboratory studies the mechanisms by which complex sounds, such as speech, are processed by the auditory system. We hypothesize that the auditory system generates internal models of the sensory world, and uses these models to extract meaning from complex sensory stimuli. One potential neuronal substrate for this generative model is the massive system of descending projections from the auditory cortex to virtually every level of the subcortical auditory system. These projections are critical for shaping the response properties of neurons in the auditory periphery, but very little is known about their functional organization.
We employ electrophysiological, novel optical and advanced anatomical approaches to study the projections from the auditory cortex to subcortical structures. One specific set of issues that we address concerns the role of different cortical subnetworks in complex sound processing. For example, neurons in both cortical layer 5 and cortical layer 6 project to subcortical structures, and the neurons in these layers have very different intrinsic, integrative and synaptic properties. Our work explores the different roles that these groups of neurons play in the processing of complex sound.
Clinical/Translational : My patient care work is focused on aging and neurodegenerative disease. Consequently, our laboratory has an interest aging-related auditory network dysfunction, particularly as it relates to changes in network properties in the auditory thalamus and cortex.
Excellence in Teaching Recognition, 2012-2019
Golden Apple Teaching Award, 2015
Advances in Medicine Award, Carle Hospital, 2016
Helen Corley Petit Scholar, 2017
Benjamin R. and Elinor W. Bullock and Edwin E. and Jeanne Bullock
Goldberg Professorial Scholar, 2017
Presidential Early Career Award for Scientists and Engineers (PECASE), 2019
Yudintsev, G, Asilador A, Sons S, Vaithiyalingam Chandra Sekaran N, Coppinger M, Nair K, Prasad M, Xiao G, Ibrahim BA, Yoshitaka Shinagawa Y, DA Llano (2021) Evidence for layer-specific connectional heterogeneity in the mouse auditory corticocollicular system. Journal of Neuroscience, In Press.
Chandrasekaran NV, Deshpande MS, Ibrahim BA, Xiao G, Shinagawa Y, Llano DA (2021) Patterns of unilateral and bilateral projections from layer 5 and 6 of the auditory cortex to the inferior colliculus in mouse. Frontiers in Systems Neuroscience, in press.
Ibrahim BA, Murphy C, Yudintsev G., Shinagawa Y, Banks MI, Llano DA (2021) Corticothalamic gating of population auditory thalamocortical transmission in mouse. eLife, May 24;10:e56645
Llano DA , Ma C, Di Fabrizio U, Taheri A, Stebbings KA, Yudintsev G, Xiao G, Kenyon RV, Berger-Wolf TY (2021) A novel dynamic network imaging analysis method reveals aging-related fragmentation of cortical networks in mouse, Network Neuroscience, Jun 21;5(2):569-590.
Lee CM, Sadowsky, RN, Schantz SL and D.A. Llano (2021) Developmental PCB exposure disrupts synaptic transmission and connectivity in the rat auditory cortex, independent of its effects on peripheral hearing threshold. eNeuro. Feb 1;8(1):ENEURO.0321-20.2021
Asilador A and D.A. Llano (2021) Top-down inference in the auditory system: Potential roles for corticofugal projections. Frontiers in Neural Circuits, Jan 22;14:615259
Lesicko A.M.H., Sons S.K. and D.A. Llano (2020) Circuit mechanisms underlying the segregation and integration of parallel processing streams in the inferior colliculus. Journal of Neuroscience, Jul 14;40(33):6328-44.
Brown JW, Taheri A, Kenyon RV, Berger-Wolf T, D.A. Llano (2020) Propagation of cortical activity via open-loop intrathalamic architectures: a computational analysis. eNeuro. Feb 25;7(1).
Liu YZ, Renteria C, Courtney CD, Ibrahim B, You S, Chaney EJ, Barkalifa R, Iyer RR, Zurauskas M, Tu H, Llano DA, Christian-Hinman CA, Boppart SA. (2020) Simultaneous two-photon activation and imaging of neural activity based on spectral-temporal modulation of supercontinuum light. Neurophotonics. Oct;7(4):045007.
Zhao Y, Maguluri G, Ferguson RD, Tu H, Paul K, Boppart SA, Llano DA , Iftimia N (2020) A portable low-cost two-photon microscope using a fiber-delivered supercontinuum generation source. Optics Letters. Feb 15;45(4):909-912.
Slater, B.J., Sons S.K., Yudintsev G., Lee C.M. and D.A. Llano (2019) Thalamocortical and intracortical inputs differentiate layer-specific mouse auditory corticocollicular neurons. Journal of Neuroscience, 39(2):256-270.
Gribkova, E.D., Ibrahim, B.A. and D.A. Llano (2018) A novel mutual information estimator to measure spike train correlations in a model thalamocortical network. Journal of Neurophysiology, Dec 1;120(6):2730-2744.
Sottile S.Y., Hackett T.A., Cai R., Llano D.A., and D.M. Caspary (2017) Presynaptic neuronal nicotinic receptors differentially shape select inputs to auditory thalamus and are negatively impacted by aging. Journal of Neuroscience, Nov 22;37(47):11377-11389.
Ibrahim B.A., Wang H., Lesicko A.M.H., Bucci B., Paul K. and D.A. Llano (2017) Effect of temperature on FAD and NADH-derived signals and neurometabolic coupling in the mouse auditory and motor cortex. JPflügers Archiv - European Journal of Physiology, Dec;469(12):1631-1649.
Patel M., Sons S., Yudintsev G., Lesicko A.M.H., Yang L., Taha G.A., Pierce S.M. and D.A. Llano (2017) Anatomical characterization of subcortical descending projections to the inferior colliculus in mouse. Journal of Comparative Neurology, Mar 1;525(4):885-900.
Lesicko A.M.H., Hristova T.S., Maigler K.C., and D.A. Llano (2016) Connectional modularity of top-down and bottom-up multimodal inputs to the lateral cortex of the inferior colliculus. Journal of Neuroscience Oct 26;36(43):11037-11050.
Paul K., Cauller L.J. and D.A. Llano (2016) Presence of a chaotic region at the sleep-wake transition in a simplified thalamocortical circuit model. Frontiers in Computational Neuroscience, Sep 1;10:91.
Stebbings, KA, Choi HW., Ravindra A., D.A. Llano (2016) The impact of aging, hearing loss and body weight on mouse hippocampal redox state, measured in brain slices using fluorescence imaging. Neurobiology of Aging, Jun;42:101-9.
Stebbings, KA, Choi HW., Ravindra A., Caspary DM, Turner JG, D.A. Llano (2016) Aging-related changes in GABAergic inhibition in the mouse auditory cortex, measured using in vitro flavoprotein autofluoresence imaging. J. Physiology. Jan 1;594(1):207-21.
Willis A.M., Slater B.J., Gribkova E., and D.A. Llano. (2015) Open-loop organization of thalamic reticular nucleus and dorsal thalamus: A computational model J. of Neurophysiology Oct;114(4):2353-67
Llano D.A., Kwok SS and V. Devanarayan (2021) Reported hearing loss in Alzheimer disease is associated with loss of brainstem and cerebellar volume. Frontiers in Human Neuroscience, in press.
Llano, D.A., and V. Devanarayan (2021). Serum phosphatidylethanolamine and lysophosphatidylethanolamine levels differentiate Alzheimer Disease from controls and predict progression from mild cognitive impairment. Journal of Alzheimer Disease, 80(1):311-319.
Llano, D.A., Issa, L.K., Devanarayan, P., and V. Devanarayan (2020). Hearing loss in Alzheimer Disease is associated with altered serum lipidomic biomarker profiles. Cells, Nov 28;9(12):E2556.
Nadhimi, Y. and D.A. Llano (2020) Does hearing loss lead to dementia? A review of the literature. Hearing Research, Jul 30:108038.
Llano, D.A., Devanarayan, P. and V. Devanarayan, (2019) VGF in cerebrospinal fluid combined with conventional biomarkers enhances prediction of conversion from MCI to Alzheimer’s Disease. Alzheimer Disease and Associated Disorders, Oct-Dec;33(4):307-314.
Esmaeeli S, Murphy K, Swords GM, Ibrahim BA, Brown JW, DA Llano (2019) Visual hallucinations, thalamocortical physiology and Dementia with Lewy Bodies: A review. Neuroscience and Biobehavioral Reviews, Aug;103:337-351.
Devanarayan, P., Devanarayan, V. and D.A. Llano (2019) Identification of a simple and novel cut-point based CSF and MRI signature for predicting Alzheimer’s disease progression that reinforces the 2018 NIA-AA research framework. Journal of Alzheimer Disease, 68(2):537-550
Swords G.M., Nguyen L.T., Mudar R.A. and D.A. Llano (2018) Auditory system dysfunction in Alzheimer Disease and its prodromal states: A review. Ageing Research Reviews, Jul;44:49-59.
Llano, DA, Mudar R, Bundela S and Devanarayan D. (2017) A multivariate predictive modeling approach reveals a novel CSF peptide signature for both Alzheimer's Disease state classification and for predicting future disease progression. PLOS One, Aug 3;12(8):e0182098.
Wang H., Kim M., Normoyle K.P. and D Llano (2016) Thermal regulation of the brain – an anatomical and physiological review for clinical neuroscientists. Frontiers in Neuroscience, Jan 21;9:528..