Luis Hernandez-Nunez

All Publications

• Emergence of Functional Heart-Brain Circuits in a Vertebrate Hernandez-Nunez, L., Avrami, J., Shi, S., Markarian, A., Boulanger-Weill, J., Zhargani-Shiraz, A., Ahrens, M., Engert, F., Fishman, M. bioRxiv. 2025

  Abstract

  The early formation of sensorimotor circuits is essential for survival. While the development and function of exteroceptive circuits and their associated motor pathways are well characterized, far less is known about the circuits that convey viscerosensory inputs to the brain and transmit visceromotor commands from the central nervous system to internal organs. Technical limitations, such as the in utero development of viscerosensory and visceromotor circuits and the invasiveness of procedures required to access them, have hindered studies of their functional development in mammals. Using larval zebrafish—which are genetically accessible and optically transparent—we tracked, in vivo, how cardiosensory and cardiomotor neural circuits assemble and begin to function. We uncovered a staged program. First, a minimal efferent circuit suffices for heart-rate control: direct brain-to-heart vagal motor innervation is required, intracardiac neurons are not, and heart rate is governed exclusively by the motor vagus nerve. Within the hindbrain, we functionally localize a vagal premotor population that drives this early efferent control. Second, sympathetic innervation arrives and enhances the dynamics and amplitude of cardiac responses, as neurons in the most anterior sympathetic ganglia acquire the ability to drive cardiac acceleration. These neurons exhibit proportional, integral, and derivative–like relationships to heart rate, consistent with controller motifs that shape gain and dynamics. Third, vagal sensory neurons innervate the heart. Distinct subsets increase activity when heart rate falls or rises, and across spontaneous fluctuations, responses to aversive stimuli, and optogenetically evoked cardiac perturbations, their dynamics are captured by a single canonical temporal kernel with neuron-specific phase offsets, supporting a population code for heart rate. This temporally segregated maturation isolates three experimentally tractable regimes—unidirectional brain-to-heart communication, dual efferent control, and closed-loop control after sensory feedback engages—providing a framework for mechanistic dissection of organism-wide heart–brain circuits.

• Imaging whole-brain activity to understand behavior. Nature reviews. Physics Lin, A., Witvliet, D., Hernandez-Nunez, L., Linderman, S. W., Samuel, A. D., Venkatachalam, V. 2022; 4 (5): 292-305

  Abstract

  The brain evolved to produce behaviors that help an animal inhabit the natural world. During natural behaviors, the brain is engaged in many levels of activity from the detection of sensory inputs to decision-making to motor planning and execution. To date, most brain studies have focused on small numbers of neurons that interact in limited circuits. This allows analyzing individual computations or steps of neural processing. During behavior, however, brain activity must integrate multiple circuits in different brain regions. The activities of different brain regions are not isolated, but may be contingent on one another. Coordinated and concurrent activity within and across brain areas is organized by (1) sensory information from the environment, (2) the animal's internal behavioral state, and (3) recurrent networks of synaptic and non-synaptic connectivity. Whole-brain recording with cellular resolution provides a new opportunity to dissect the neural basis of behavior, but whole-brain activity is also mutually contingent on behavior itself. This is especially true for natural behaviors like navigation, mating, or hunting, which require dynamic interaction between the animal, its environment, and other animals. In such behaviors, the sensory experience of an unrestrained animal is actively shaped by its movements and decisions. Many of the signaling and feedback pathways that an animal uses to guide behavior only occur in freely moving animals. Recent technological advances have enabled whole-brain recording in small behaving animals including nematodes, flies, and zebrafish. These whole-brain experiments capture neural activity with cellular resolution spanning sensory, decision-making, and motor circuits, and thereby demand new theoretical approaches that integrate brain dynamics with behavioral dynamics. Here, we review the experimental and theoretical methods that are being employed to understand animal behavior and whole-brain activity, and the opportunities for physics to contribute to this emerging field of systems neuroscience.

  View details for DOI 10.1038/s42254-022-00430-w

  View details for PubMedID 37409001

  View details for PubMedCentralID PMC10320740

• Automated Control of Odor Dynamics for Neurophysiology and Behavior Hernandez-Nunez, L., Samuel, A. D. T. OXFORD UNIV PRESS. 2021

  View details for Web of Science ID 000730264600187

• Internal state configures olfactory behavior and early sensory processing in Drosophila larvae SCIENCE ADVANCES Vogt, K., Zimmerman, D. M., Schlichting, M., Hernandez-Nunez, L., Qin, S., Malacon, K., Rosbash, M., Pehlevan, C., Cardona, A., Samuel, A. D. T. 2021; 7 (1)

  View details for DOI 10.1126/sciadv.abd6900

  View details for Web of Science ID 000605159200029

• Synchronous and opponent thermosensors use flexible cross-inhibition to orchestrate thermal homeostasis Science Advances Hernandez-Nunez, L., Chen, A., Budelli, G., Berck, M., Richter, V., Rist, A., Thum, A., Cardona, A., Klein, M., Garrity, P., Samuel, A. D. 2021

  View details for DOI 10.1126/sciadv.abg6707

• A Hybrid Compact Neural Architecture for Visual Place Recognition IEEE ROBOTICS AND AUTOMATION LETTERS Chancan, M., Hernandez-Nunez, L., Narendra, A., Barron, A. B., Milford, M. 2020; 5 (2): 993-1000

  View details for DOI 10.1109/LRA.2020.2967324

  View details for Web of Science ID 000511836400002

• The wiring diagram of a glomerular olfactory system. eLife Berck, M. E., Khandelwal, A., Claus, L., Hernandez-Nunez, L., Si, G., Tabone, C. J., Li, F., Truman, J. W., Fetter, R. D., Louis, M., Samuel, A. D., Cardona, A. 2016; 5

  Abstract

  The sense of smell enables animals to react to long-distance cues according to learned and innate valences. Here, we have mapped with electron microscopy the complete wiring diagram of the Drosophila larval antennal lobe, an olfactory neuropil similar to the vertebrate olfactory bulb. We found a canonical circuit with uniglomerular projection neurons (uPNs) relaying gain-controlled ORN activity to the mushroom body and the lateral horn. A second, parallel circuit with multiglomerular projection neurons (mPNs) and hierarchically connected local neurons (LNs) selectively integrates multiple ORN signals already at the first synapse. LN-LN synaptic connections putatively implement a bistable gain control mechanism that either computes odor saliency through panglomerular inhibition, or allows some glomeruli to respond to faint aversive odors in the presence of strong appetitive odors. This complete wiring diagram will support experimental and theoretical studies towards bridging the gap between circuits and behavior.

  View details for DOI 10.7554/eLife.14859

  View details for PubMedID 27177418

  View details for PubMedCentralID PMC4930330

• Erratum: Multimodal stimulus coding by a gustatory sensory neuron in Drosophila larvae. Nature communications van Giesen, L., Hernandez-Nunez, L., Delasoie-Baranek, S., Colombo, M., Renaud, P., Bruggmann, R., Benton, R., Samuel, A. D., Sprecher, S. G. 2016; 7: 11028

  View details for DOI 10.1038/ncomms11028

  View details for PubMedID 26972323

  View details for PubMedCentralID PMC4793080

• Reverse-correlation analysis of navigation dynamics in Drosophila larva using optogenetics. eLife Hernandez-Nunez, L., Belina, J., Klein, M., Si, G., Claus, L., Carlson, J. R., Samuel, A. D. 2015; 4

  Abstract

  Neural circuits for behavior transform sensory inputs into motor outputs in patterns with strategic value. Determining how neurons along a sensorimotor circuit contribute to this transformation is central to understanding behavior. To do this, a quantitative framework to describe behavioral dynamics is needed. In this study, we built a high-throughput optogenetic system for Drosophila larva to quantify the sensorimotor transformations underlying navigational behavior. We express CsChrimson, a red-shifted variant of channelrhodopsin, in specific chemosensory neurons and expose large numbers of freely moving animals to random optogenetic activation patterns. We quantify their behavioral responses and use reverse-correlation analysis to uncover the linear and static nonlinear components of navigation dynamics as functions of optogenetic activation patterns of specific sensory neurons. We find that linear-nonlinear models accurately predict navigational decision-making for different optogenetic activation waveforms. We use our method to establish the valence and dynamics of navigation driven by optogenetic activation of different combinations of bitter-sensing gustatory neurons. Our method captures the dynamics of optogenetically induced behavior in compact, quantitative transformations that can be used to characterize circuits for sensorimotor processing and their contribution to navigational decision making.

  View details for DOI 10.7554/eLife.06225

  View details for PubMedID 25942453

  View details for PubMedCentralID PMC4466337

• Sensory determinants of behavioral dynamics in Drosophila thermotaxis. Proceedings of the National Academy of Sciences of the United States of America Klein, M., Afonso, B., Vonner, A. J., Hernandez-Nunez, L., Berck, M., Tabone, C. J., Kane, E. A., Pieribone, V. A., Nitabach, M. N., Cardona, A., Zlatic, M., Sprecher, S. G., Gershow, M., Garrity, P. A., Samuel, A. D. 2015; 112 (2): E220-9

  Abstract

  Complex animal behaviors are built from dynamical relationships between sensory inputs, neuronal activity, and motor outputs in patterns with strategic value. Connecting these patterns illuminates how nervous systems compute behavior. Here, we study Drosophila larva navigation up temperature gradients toward preferred temperatures (positive thermotaxis). By tracking the movements of animals responding to fixed spatial temperature gradients or random temperature fluctuations, we calculate the sensitivity and dynamics of the conversion of thermosensory inputs into motor responses. We discover three thermosensory neurons in each dorsal organ ganglion (DOG) that are required for positive thermotaxis. Random optogenetic stimulation of the DOG thermosensory neurons evokes behavioral patterns that mimic the response to temperature variations. In vivo calcium and voltage imaging reveals that the DOG thermosensory neurons exhibit activity patterns with sensitivity and dynamics matched to the behavioral response. Temporal processing of temperature variations carried out by the DOG thermosensory neurons emerges in distinct motor responses during thermotaxis.

  View details for DOI 10.1073/pnas.1416212112

  View details for PubMedID 25550513

  View details for PubMedCentralID PMC4299240

• Limits of Feedback Control in Bacterial Chemotaxis (vol 10, e1003694, 2014) PLOS COMPUTATIONAL BIOLOGY Dufour, Y. S., Fu, X., Hernandez-Nunez, L., Emonet, T. 2014; 10 (12)

  View details for DOI 10.1371/journal.pcbi.1004069

  View details for Web of Science ID 000346656700055

• Adaptability of non-genetic diversity in bacterial chemotaxis. eLife Frankel, N. W., Pontius, W., Dufour, Y. S., Long, J., Hernandez-Nunez, L., Emonet, T. 2014; 3

  Abstract

  Bacterial chemotaxis systems are as diverse as the environments that bacteria inhabit, but how much environmental variation can cells tolerate with a single system? Diversification of a single chemotaxis system could serve as an alternative, or even evolutionary stepping-stone, to switching between multiple systems. We hypothesized that mutations in gene regulation could lead to heritable control of chemotactic diversity. By simulating foraging and colonization of E. coli using a single-cell chemotaxis model, we found that different environments selected for different behaviors. The resulting trade-offs show that populations facing diverse environments would ideally diversify behaviors when time for navigation is limited. We show that advantageous diversity can arise from changes in the distribution of protein levels among individuals, which could occur through mutations in gene regulation. We propose experiments to test our prediction that chemotactic diversity in a clonal population could be a selectable trait that enables adaptation to environmental variability.

  View details for DOI 10.7554/eLife.03526

  View details for PubMedID 25279698

  View details for PubMedCentralID PMC4210811