During my MD/PhD I became interested in neural circuits and neurological disorders such as Parkinson’s and dystonia. Frustrated by poor treatment options, I left a career in medicine to do basic research into motor control. My postdoc at MIT leveraged advantages songbirds and revealed principles of basal ganglia (BG) dependent trial-and-error learning. At Cornell I built a unique lab and training environment that compares mechanisms of motor control/learning in three species: songbirds, parrots, and mice. All research programs combine high channel count awake-behaving electrophysiology, closed-loop optogenetics, and machine learning-guided behavioral analysis to study how distributed brain circuits linking cortex, cerebellum, basal ganglia and brainstem function during natural behaviors. Here we leverage our recent progress in bringing 21st century experimental tools to parrots: this proposal combines AI-powered vocal analysis tools with neural recordings and local brain inactivations in freely socializing parrots. My lab’s guiding philosophy is that a comparative approach in systems neuroscience, in which distinct species and effectors are studied side-by-side, is important for discovering general principles of brain function and dysfunction.
1. Gadagkar V, Puzerey P, Chen R, Baird-Daniel E, Farhang A, Goldberg JH. Dopamine neurons encode performance error in singing birds. Science. 2016 Dec 9;354(6317):1278-1282.
2. Roeser A, Gadagkar V, Das A, Puzerey PA, Kardon B, Goldberg JH. Dopaminergic error signals retune to social feedback during courtship. Nature. 2023 Sep 27.
3. Bollu T,* Ito B*, Whitehead SC, Kardon B, Liu MH, Goldberg JH. Cortex-dependent corrections as the tongue reaches for and misses targets. Nature. 2021 Jun;594(7861):82-87.
4. Brendan S. Ito*, Yongjie Gao*, Brian Kardon, Jesse H. Goldberg. A collicular map for touch-guided tongue control. Nature. 2025 Jan;637(8048):1143-1151. pdf
1. R01 Neural mechanisms of performance evaluation during motor sequence learning 7/2020-6/2025
Goal: To test if limbic inputs to dopamine neurons evaluate the quality of performance in singing zebra finches.
Role: PI
2. Pew Innovation Fund. Neural mechanisms of parental care in songbirds and mice 3/2024-20/2027
Goal: To test roles of dopamine and oxytocin systems as songbirds feed their young
Role: PI (Froemke, NYU, Co-PI)
3. Brain Research Fdn. Towards Dopaminergic Mechanisms of Observational Learning 6/2024-5/2026
Goal: To test roles of dopamine signals during observed allofeeding in songbirds
Role: PI
4. R01 Neural Mechanisms of miss- and touch-guided sensorimotor corrections 8/2024-7/2029
Goal: To dissect neural circuits for tongue motor control in mice.
Role: PI
1. NIH R34. Neural mechanisms of social communication in parrots 7/2021-6/2023
Goal: To identify how recurrent cortico-basal ganglia loops control vocal production in parrots.
Role: PI
2. NIH R01. Neural mechanisms of performance evaluation during motor learning 9/2015-6/2020
Goal: To test if dopamine neurons evaluate the quality of performance in singing birds.
Role: PI
3. Pew Trusts. Neural mechanisms of performance evaluation during motor learning 9/2015-6/2020
Goal: Test for vocal error signals in songbird dopamine-basal ganglia pathways.
Role: PI
4. NIH DP2 Identifying Pathways for Motor variability in the mammalian brain. 9/2015-9/2020
Goal: Develop novel motor learning paradigms in mice. Role: PI
5. NIH R21 MOTES: Micro-scale opto-electronically transduced electrode sites 9/2016-7/2018
Goal: Develop and test a novel wireless neural recording technology based on a light-powered voltage sensor.
Role: Co-PI
6. Dystonia Medical Research Foundation. 9/2018-8/2020
Machine learning guided DBS to cure neurological disease.
Goal: Develop machine learning algorithms to quantify pathological mouse forelimb and tongue kinematics.
Role: PI
7. NIH U01. Injectable Microscale Opto-electronically Transduced Electrodes. 9/2018-9/2021
Goal: To develop and test a novel wireless neural recording technology based on a light-powered voltage sensor.
Role: Co-PI
B. Positions, Scientific Appointments, and Honors
Positions and Employment
2025-Present Dr. David and Dorothy Joslovitz Merksamer Professor
2024-Present Full Professor, Department of Neurobiology and Behavior, Cornell University
2022 Jan-Jun Visiting Scientist, Mediterranean Institute for Neurobiology, INSERM, Marseille, FR
2019-2024 Associate Professor, Department of Neurobiology and Behavior, Cornell University
2012-2019 Assistant Professor, Department of Neurobiology and Behavior, Cornell University
2005-2012 Postdoc, Laboratory of Michale Fee, McGovern Institute for Brain Research, M.I.T.
1997-2005 Medical Scientist Training Program, Laboratory of Rafael Yuste, Columbia University
2001 Methods in Computational Neuroscience, Marine Biological Lab, Woods Hole, MA.
1995-1997 Undergraduate research fellow, Laboratory of Daniel Alkon, NINDS, NIH.
Other Experience and Professional Memberships
2023-present Co-Director, Cornell AI Initiative
2020-present Editorial board, eLife
2019-present SfN Committee for Animals in Research (CAR)
2017-present Scientific Advisory Committee, Dystonia Medical Research Foundation
2014-present Ad hoc member of NSF/NIH/NINDS Study Sections
2014-2016 Grant reviewer, Israel Science Foundation
2010-present Member, International basal ganglia society
2017-2018 Grant reviewer, Human Frontiers Science Program
2015 Co-organizer, Thalamus and corticothalamic interactions, HHMI, Ashburn, VA
2013-2016 Reviewer, Computational and Systems Neuroscience Meeting, Salt Lake City, UT
2013 Grant reviewer, Neurological Foundation of New Zealand
1999-present Member, Society for Neuroscience
2012-present Manuscript Reviewer: Science, Nature, Cell, Neuron, Nature Neuroscience, Journal of Neurophysiology, Journal of Neuroscience, Nature Communications, Journal of Physiology, eLife, Royal Proceedings B, Brain and Behavioral Sciences, PLOS Biology, Scientific Reports
Honors
2024 Stephen H. Weiss Teaching Award, Cornell University
2024-2025 Brain Research Foundation Seed Grant recipient
2023-2025 Pew Innovation Fund
2015-2020 NIH New Innovator
2014-2018 Pew Biomedical Scholar
2016 Kavli Fellow
2013-2016 Klingenstein Fellowship in the Neurosciences
2010-2015 K99/R00 Pathway to Independence Award, NINDS
2009-2010 Charles King Trust Postdoctoral Fellowship
2005-2008 Damon Runyon Research Foundation Postdoctoral Fellowship
2004 Dean’s Award for best Ph.D. thesis, Columbia University
2004 Ph.D. thesis awarded with distinction, Columbia University
1997-2005 Medical Scientist Training Program Scholarship
1997 Honors Thesis in Biology, Haverford College
1997 Phi Beta Kappa Society, Haverford College
C. Contributions to Science
1. Using deep learning for high-resolution behavioral analysis across species. We develop custom analytical tools to resolve important aspects of animal behavior and combine these tools with methods for neural recording and manipulation. In mice, we combined kilohertz framerate videography, deep learning based image segmentation, high channel count electrophysiology and closed-loop optogenetic manipulation of neural activity to discover that cortical and collicular circuits play distinct roles in miss- and touch-guided online lingual corrections as mice drink from a water spout. In songbirds, we innovated novel vocalization outlier detection methods, using reconstruction errors from variational autoencoders, to discover that lateral habenula lesions caused species-atypical songs in zebra finches. In parrots, we are developing new behavioral paradigms and deep learning methods to quantify large vocal datasets and have, so far, discovered that the parrot and songbird neural circuits appear to use distinct pathways for the generation of structured versus exploratory vocalizations.
a. Bollu T,* Ito B*, Whitehead SC, Kardon B, Liu MH, Goldberg JH. Cortex-dependent corrections as the tongue reaches for and misses targets. Nature. 2021 Jun;594(7861):82-87.
b. Roeser A, Teoh HK, Chen R, Cohen I, Goldberg J. The songbird lateral habenula projects to dopaminergic midbrain and is important for normal vocal development. bioRxiv 2023:2023.06.21.545765. https://doi.org/10.1101/2023.06.21.545765.
c. Zhao Z, Teoh HK, Carpenter J, Nemon F, Kardon B, Cohen I, Goldberg JH. Anterior forebrain pathway in parrots is necessary for producing learned vocalizations with individual signatures. Current Biology. 2023 Dec 18;33(24):5415-5426.
d. Ito B*, Gao Y*, Kardon B, Goldberg JH. A collicular map for touch-guided tongue control. Nature. 2025 Jan;637(8048):1143-1151
2. Discovery of performance error signals in songbirds. An unanswered question was how performance is evaluated as ‘good’ or ‘bad’ during practice. It was well established that dopamine activity contributes to reinforcement learning by encoding reward prediction error in tasks where animals learn for primary rewards such as food or juice. But it was unknown if dopamine could also encode performance error in tasks that did not involve reward. To test if dopamine encodes performance error, we recorded dopamine neurons in singing birds while controlling perceived error with distorted auditory feedback. Remarkably, dopamine activity encoded performance just like reward: phasic bursts following better-than-predicted outcomes, and phasic pauses following worse-than-predicted ones. We next identified origins of dopaminergic error signals in a ventral pallidal region outside the classic song system, revealing a previously unidentified ‘actor/critic’ circuit motif inside the songbird brain. This discovery demonstrated that circuit motif associated with drug addiction and foraging in mammals is ancestral and can be repurposed for learning a motor sequence like birdsong. Finally, dopamine is, of course, not the only neuromodulator likely to be important for a complex behavior like birdsong learning. The basal forebrain also has strong cholinergic projections to motor cortical areas, yet the role of acetylcholine for motor learning remained unclear. We found that manipulation of cholinergic signaling in vocal motor cortex of juvenile birds did not affect vocal babbling, yet chronic blockade over weeks impaired learning, resulting in an impoverished song with excess variability, abnormal acoustic features and reduced similarity to tutor song.
a. Gadagkar V, Puzerey P, Chen R, Baird-Daniel E, Farhang A, Goldberg JH. Dopamine neurons encode performance error in singing birds. Science. 2016 Dec 9;354(6317):1278-1282.
b. Puzerey P, Maher K, Chen R, Prasad N, Goldberg JH. Vocal learning in songbirds requires cholinergic signaling in a motor cortex-like nucleus. J Neurophysiol. 2018 Oct 1;120(4):1796-1806.
c. Chen R, Puzerey PA, Roeser AC, Riccelli TE, Podury A, Maher K, Farhang AR, Goldberg JH. Songbird Ventral Pallidum Sends Diverse Performance Error Signals to Dopaminergic Midbrain. Neuron. 2019 May 11;doi: 10.1016/j.neuron.2019.04.038.
3. Determining how signals propagate through songbird BG-thalamic circuits during behavior. I performed the first recordings from all six BG classes in singing juvenile birds, resulting in a complete classification of intrinsic BG circuitry, identification of sparse temporally precise discharge in striatal medium spiny neurons, the discovery of two pallidal pathways homologous to primates, and a new model of BG output to the thalamus. The BG have several cell classes, but one main output: GABAergic pallidal neurons that project to the thalamus. In the classical model, thalamic activity is suppressed by the tonic inhibition of these pallidal inputs, and pauses in pallidal firing enable thalamic activation. My studies overturned these assumptions. I recorded, for the first time, simultaneously from connected pairs of pallidal terminals and thalamic neurons during behavior, and found that (1) Connected pallidal and thalamic neurons fired in concert at high rates (>200 Hz). (2) Thalamic spiking was not restricted to pallidal pauses. (3) Thalamic spikes were time-locked to pallidal spikes with submillisecond precision. Together, these findings revised the predominant model that BG outputs silence thalamic activity, and instead showed that the BG control thalamic spike timing.
a. Goldberg JH, Farries MA and Fee MS. Integration of cortical and pallidal inputs in the basal ganglia-recipient thalamus of singing birds. Journal of Neurophysiology 2012 Sep;108(5):1403-29.
b. Goldberg JH, Adler A, Bergman H, and Fee MS. Singing related neural activity distinguishes two classes of putative pallidal neuron in the songbird basal ganglia: Comparison to the primate internal and external pallidal segments. Journal of Neuroscience. 2010 May 19;30(20):7088-98
c. Goldberg JH and Fee MS. Singing related neural activity distinguishes four classes of putative striatal neuron in the songbird basal ganglia. Journal of Neurophysiology. 2010 Apr;103(4):2002-14.
d. Pidoux M, Bollu T, Riccelli T, Goldberg JH. Origins of basal ganglia output signals in singing juvenile birds. J Neurophysiol. 2014 Nov 12:jn.00635.2014. doi: 10.1152/jn.00635.2014.
4. Determining neural circuits driving motor variability during learning. The basal ganglia (BG), thalamus and cortex form an evolutionarily conserved brain loop widely implicated in human disease and trial-and-error learning. The first big question I addressed in songbirds, a tractable model system for BG research, relates to how exploratory behaviors are generated – the ‘trial’ part of learning. Juvenile songbirds babble, and the variability of their vocalizations is thought to represent motor exploration essential for learning. It was long assumed that the uncoordinated, variable motor behavior of juveniles was the de facto output of an immature motor system. Yet I found that variability is instead actively generated by BG-related circuits. Specifically, lesions to the motor thalamus abolished vocal variability, resulting in a highly stereotyped song. It was as if a beginner tennis player, spraying balls all over the court, was suddenly hitting the same shot over and over. Yet lesioning the BG inputs to the motor thalamus did not affect babbling at all. This result was surprising because canonical models assumed that the thalamus was principally a relay from BG to cortex, and yet I observed that thalamic motor function did not require the BG. I next performed the first simultaneous recordings of thalamic neurons and their BG inputs in any model system, allowing me to analyze the origins of thalamic premotor signals. I discovered that inputs to the thalamus from a motor cortical nucleus, and not inputs from the BG, drove thalamic premotor activity during babbling. Activity in the homologous part of the human thalamus controls movement initiation and drives Parkinsonian tremor, and was thought to be primarily controlled by BG inputs. Yet these studies suggest a different view: motor cortex, not the BG, drives thalamic premotor signals during behavior, and a previously overlooked cortico-thalamocortical loop generates motor exploration during learning.
a. Goldberg JH and Fee MS. Vocal babbling in songbirds requires the basal ganglia-recipient motor thalamus but not the basal ganglia. Journal of Neurophysiology. 2011 Jun;105(6):2729-39.
b. Aronov D, Veit L, Goldberg JH, Fee MS. Two distinct modes of forebrain circuit dynamics underlie temporal patterning in the vocalizations of young songbirds. Journal of Neuroscience. 2011 Nov 9;31(45): 16353-68.
c. Olveczky BP, Otchy T, Goldberg JH, Aronov D, Fee MS. Changes in the neural control of a complex motor sequence during learning. Journal of Neurophysiology. 2011 Jul;106(1):3867.
d. Goldberg JH and Fee MS. A cortical motor nucleus drives the basal ganglia-recipient thalamus in singing birds. Nature Neuroscience. 2012 Feb 12;15(4):620-7.
5. Identifying ‘canonical’ microcircuits and associated dendritic functions in the neocortex. My PhD dissertation in Rafael Yuste’s lab at Columbia University focused on inhibitory microcircuits of the cortex. I tested the big idea that the cortex has may be composed of one canonical microcircuit repeated millions of times over the surface of the brain, i.e. it has a modular organization. If this is the case, then studying any one module could reveal basic principles about the entire structure. To test this hypothesis, I used electrophysiology, two photon calcium imaging, immunohistochemistry and cellular reconstructions, to test whether microcircuitry varied across widespread cortical regions. For example, I discovered that specialized potassium channels restrict dendritic calcium accumulations in one cell class, while low voltage activated calcium channels mediate global calcium signals in others. Meanwhile, Ca-permeable AMPA receptors contribute to calcium microdomains in aspiny dendrites of PV interneurons across cortex. This body of work showed, for the first time, that the dendrites of inhibitory interneurons were active structures, expressing a wide variety of voltage gated and synaptic ion channels in a cell class specific manner. Further, interneuronal subclass specializations were invariant across visual, sensory and motor cortices, supporting the overarching hypothesis of modular cortical architecture. This modular view of brain function influenced my thinking in the clinic. When I confronted the complexity of neurological disease in medical school, I decided that the ideal way to understand disease mechanims would be to isolate one basal ganglia module and study it in relation to the specific behavior it controls. This is why I chose the songbird: it is a model system with a discrete basal ganglia module devoted to natural trial and error motor learning.
a. Goldberg JH, Yuste R, Tamas G. Ca2+ imaging of mouse neocortical interneuron dendrites: Contribution of Ca2+-permeable AMPA and NMDA receptors to subthreshold Ca2+dynamics. Journal of Physiology (Previewed article). 2003 Aug 15;551:67-78.
b. Goldberg JH, Tamas G, Yuste R. Ca2+ imaging of mouse neocortical interneuron dendrites: Ia-type K+ channels control action potential backpropagation. Journal of Physiology (Previewed article). 2003 Aug 15;551:49-65.
c. Goldberg JH, Lacefield CO, Yuste R. Global dendritic calcium spikes in mouse layer 5 low-threshold spiking (LTS) interneurones: implications for control of pyramidal bursting. Journal of Physiology. 2004 Jul 15;558(Pt 2):465-78.
d. Goldberg JH, Tamas G, Aronov D, Yuste R. Calcium microdomains in aspiny dendrites. Neuron (Cover article). 2003 Nov 13;40(4):807-21.
Complete List of Published Work in MyBibliography:
https://www.ncbi.nlm.nih.gov/myncbi/jesse.goldberg.1/bibliography/public/