
Research in the Brainard laboratory focuses primarily on the question of how experience, particularly during early life, shapes the functioning of the nervous system using a combination of behavioral and neurophysiological techniques to investigate the mechanisms underlying vocal learning in songbirds.
The study of song learning offers the advantages of a well described behavior that exhibits a variety of general features of learning, and that is subserved by a discrete and extensively investigated set of brain regions. Because many species of songbirds breed well in captivity and develop rapidly, they are well suited for studying processes of developmental plasticity. Song learning proceeds in two stages. First, during a period of sensory learning, young birds listen to and memorize the song of an adult 'tutor'. Then, during a period of sensorimotor learning, they use auditory feedback to gradually refine their own initially rambling vocalizations so that they progressively resemble the previously memorized tutor song. Normal song learning requires appropriate experience during a sensitive period in early development, although recent studies have shown that auditory feedback also contributes to the adult maintenance of precisely calibrated vocal output. These features make song learning a useful model for studying the mechanisms that contribute to vertebrate sensory and sensorimotor learning in general, and to certain components of human language learning in particular; speech acquisition exhibits strikingly similar requirements for memorization and vocal practice during early development and for maintained auditory feedback throughout life.
Contributions of auditory feedback to song learning and maintenance
Prior experiments combining behavioral analysis of song with targeted lesions of song system nuceli suggest that signals arising from the songbird basal ganglia (the 'anterior forebrain pathway' or AFP) are necessary throughout life for the feedback-based modification of song (Brainard and Doupe 2000). Current experiments using feedback alteration, neural recording and microstimulation are designed to further test the hypothesis that this basal-ganglia circuit provides an error signal that reflects the quality of match between a bird's own vocalizations and the memorized tutor song.
Feedback alteration: To achieve a controlled and reversible alteration of auditory feedback, we have developed a computerized system that detects song elements (as the bird is singing) and generates sounds that are superimposed on, and hence alter, the normal auditory feedback that the bird experiences. This manipulation can cause acute changes to ongoing song production (such as alterations to the timing or sequencing of song elements). This indicates that auditory feedback influences vocal production on a moment by moment basis, as it does in humans. Extended exposure to feedback altered in this manner can also lead to persistent changes in song, indicating that altered feedback elicits neural signals that are capable of driving plastic changes in the song motor program. Ongoing experiments are designed to further assess the capacity of the song system to adapt to systematic alterations of auditory feedback.
Chronic neural recording: To characterize the location and nature of neural signals generated by alteration of auditory feedback, we are using chronic extracellular recordings from awake singing birds during conditions of normal and altered feedback. Initial experiments are focussing on the AFP, although this technique will also enable tracing the transformation of feedback at earlier stages of auditory processing.
Microstimulation: Neural signals elicited by feedback alteration could in principle participate in instructing changes in the motor pathway. Artificial introduction of patterned activity to the nervous system, by microstimulation, will allow testing the sufficiency of such signals to drive changes in the motor program for song. We are currently assessing the influence on vocal production of song-triggered microstimulation of the AFP. Output from this pathway converges on motor neurons within the pathway for vocal production. Because song structure is normally very stereotyped, behavioral analysis will enable detection both of acute and lasting effects of altering neural activity on the motor program for song.
Developmental regulation of plasticity
Sensory learning of song occurs during a well characterized 'sensitive period' beyond which the nervous system is progressively less influenced by exposure to other song models. Similarly, in the final stages of sensorimotor learning there is a decline in the susceptibility of song production to disruption by altered experience. Evidence for this includes experiments that have shown that the degree to which song deteriorates following loss of auditory feedback decreases progressively with age (Brainard and Doupe 2001). As we explore the mechanisms underlying sensory and sensorimotor learning, a general question of interest is how these mechanisms are developmentally altered so that the nervous system becomes less susceptible to the influence of experience.
Reinforcement learning
In addition to the critical role of auditory experience during song learning, non-auditory factors, especially arising from social interactions, help shape what songs are memorized and produced. For example, male birds with a variable repertoire of songs will preferentially retain those songs that elicit courtship displays from females. This indicates that rather global reinforcement signals (in this case dependent on visual cues from the female) can shape subsequent vocal production. Similar reinforcement signals play a widespread role in learning, and indeed refinement of song based on feedback evaluation may depend in part on global reinforcement signals that indicate quality of match between actual vocal production and a desired perceptual target. In other vertebrates, reinforcement learning is mediated in part by dopaminergic pathways originating from the midbrain. In songbirds, these dopaminergic pathways project heavily to the AFP and other structures of the song system, and are thus well situated to provide signals that could modulate or guide song learning. We are preparing to explore how these pathways contribute to different stages of vocal motor learning using targeted neural recording and microstimulation.
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Cellular transcriptomics reveals evolutionary identities of songbird vocal circuits. Science. 2021 Feb 12; 371(6530). Colquitt BM, Merullo DP, Konopka G, Roberts TF, Brainard MS. PMID: 33574185.
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Acetylcholine acts on songbird premotor circuitry to invigorate vocal output. Elife. 2020 05 19; 9. Jaffe PI, Brainard MS. PMID: 32425158.
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Learning is enhanced by tailoring instruction to individual genetic differences. Elife. 2019 09 17; 8. Mets DG, Brainard MS. PMID: 31526480.
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The Avian Basal Ganglia Are a Source of Rapid Behavioral Variation That Enables Vocal Motor Exploration. J Neurosci. 2018 11 07; 38(45):9635-9647. Kojima S, Kao MH, Doupe AJ, Brainard MS. PMID: 30249800.
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An automated approach to the quantitation of vocalizations and vocal learning in the songbird. PLoS Comput Biol. 2018 08; 14(8):e1006437. Mets DG, Brainard MS. PMID: 30169523.
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Zebra finches are sensitive to combinations of temporally distributed features in a model of word recognition. J Acoust Soc Am. 2018 08; 144(2):872. Knowles JM, Doupe AJ, Brainard MS. PMID: 30180710.
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Draft genome assembly of the Bengalese finch, Lonchura striata domestica, a model for motor skill variability and learning. Gigascience. 2018 03 01; 7(3):1-6. Colquitt BM, Mets DG, Brainard MS. PMID: 29618046.
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Genetic variation interacts with experience to determine interindividual differences in learned song. Proc Natl Acad Sci U S A. 2018 01 09; 115(2):421-426. Mets DG, Brainard MS. PMID: 29279376.
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Vocal learning promotes patterned inhibitory connectivity. Nat Commun. 2017 12 13; 8(1):2105. Miller MN, Cheung CYJ, Brainard MS. PMID: 29235480.
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Discrete Circuits Support Generalized versus Context-Specific Vocal Learning in the Songbird. Neuron. 2017 Dec 06; 96(5):1168-1177.e5. Tian LY, Brainard MS. PMID: 29154128.
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Timing during transitions in Bengalese finch song: implications for motor sequencing. J Neurophysiol. 2017 09 01; 118(3):1556-1566. Troyer TW, Brainard MS, Bouchard KE. PMID: 28637816.
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Auditory-induced neural dynamics in sensory-motor circuitry predict learned temporal and sequential statistics of birdsong. Proc Natl Acad Sci U S A. 2016 08 23; 113(34):9641-6. Bouchard KE, Brainard MS. PMID: 27506786.
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An Adapting Auditory-motor Feedback Loop Can Contribute to Generating Vocal Repetition. PLoS Comput Biol. 2015 Oct; 11(10):e1004471. Wittenbach JD, Bouchard KE, Brainard MS, Jin DZ. PMID: 26448054.
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Role of the site of synaptic competition and the balance of learning forces for Hebbian encoding of probabilistic Markov sequences. Front Comput Neurosci. 2015; 9:92. Bouchard KE, Ganguli S, Brainard MS. PMID: 26257637.View in: PubMed Mentions:
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Editorial overview: communication and language: animal communication and human language. Curr Opin Neurobiol. 2014 Oct; 28:v-viii. PMID: 25192981.
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Neural encoding and integration of learned probabilistic sequences in avian sensory-motor circuitry. J Neurosci. 2013 Nov 06; 33(45):17710-23. PMID: 24198363.
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Translating birdsong: songbirds as a model for basic and applied medical research. Annu Rev Neurosci. 2013 Jul 08; 36:489-517. PMID: 23750515.
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Vocal learning is constrained by the statistics of sensorimotor experience. Proc Natl Acad Sci U S A. 2012 Dec 18; 109(51):21099-103. PMID: 23213223.
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Variable sequencing is actively maintained in a well learned motor skill. J Neurosci. 2012 Oct 31; 32(44):15414-25. PMID: 23115179.
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Covert skill learning in a cortical-basal ganglia circuit. Nature. 2012 May 20; 486(7402):251-5. PMID: 22699618.
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Mechanisms and time course of vocal learning and consolidation in the adult songbird. J Neurophysiol. 2011 Oct; 106(4):1806-21. PMID: 21734110.
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Learning the microstructure of successful behavior. Nat Neurosci. 2011 Mar; 14(3):373-80. Charlesworth JD, Tumer EC, Warren TL, Brainard MS. PMID: 21278732.
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Linked control of syllable sequence and phonology in birdsong. J Neurosci. 2010 Sep 29; 30(39):12936-49. Wohlgemuth MJ, Sober SJ, Brainard MS. PMID: 20881112.
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Social context rapidly modulates the influence of auditory feedback on avian vocal motor control. J Neurophysiol. 2009 Oct; 102(4):2485-97. Sakata JT, Brainard MS. PMID: 19692513.
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Adult birdsong is actively maintained by error correction. Nat Neurosci. 2009 Jul; 12(7):927-31. Sober SJ, Brainard MS. PMID: 19525945.
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An avian basal ganglia-forebrain circuit contributes differentially to syllable versus sequence variability of adult Bengalese finch song. J Neurophysiol. 2009 Jun; 101(6):3235-45. Hampton CM, Sakata JT, Brainard MS. PMID: 19357331.
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Online contributions of auditory feedback to neural activity in avian song control circuitry. J Neurosci. 2008 Oct 29; 28(44):11378-90. Sakata JT, Brainard MS. PMID: 18971480.
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Central contributions to acoustic variation in birdsong. J Neurosci. 2008 Oct 08; 28(41):10370-9. Sober SJ, Wohlgemuth MJ, Brainard MS. PMID: 18842896.
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Social modulation of sequence and syllable variability in adult birdsong. J Neurophysiol. 2008 Apr; 99(4):1700-11. Sakata JT, Hampton CM, Brainard MS. PMID: 18216221.
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Performance variability enables adaptive plasticity of 'crystallized' adult birdsong. Nature. 2007 Dec 20; 450(7173):1240-4. Tumer EC, Brainard MS. PMID: 18097411.
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Real-time contributions of auditory feedback to avian vocal motor control. J Neurosci. 2006 Sep 20; 26(38):9619-28. Sakata JT, Brainard MS. PMID: 16988032.
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Lesions of an avian basal ganglia circuit prevent context-dependent changes to song variability. J Neurophysiol. 2006 Sep; 96(3):1441-55. Kao MH, Brainard MS. PMID: 16723412.
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Contributions of an avian basal ganglia-forebrain circuit to real-time modulation of song. Nature. 2005 Feb 10; 433(7026):638-43. Kao MH, Doupe AJ, Brainard MS. PMID: 15703748.
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Contributions of the anterior forebrain pathway to vocal plasticity. Ann N Y Acad Sci. 2004 Jun; 1016:377-94. Brainard MS. PMID: 15313786.
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What songbirds teach us about learning. Nature. 2002 May 16; 417(6886):351-8. Brainard MS, Doupe AJ. PMID: 12015616.
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Postlearning consolidation of birdsong: stabilizing effects of age and anterior forebrain lesions. J Neurosci. 2001 Apr 01; 21(7):2501-17. Brainard MS, Doupe AJ. PMID: 11264324.
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Song selectivity and sensorimotor signals in vocal learning and production. Proc Natl Acad Sci U S A. 2000 Oct 24; 97(22):11836-42. Solis MM, Brainard MS, Hessler NA, Doupe AJ. PMID: 11050217.
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Auditory feedback in learning and maintenance of vocal behaviour. Nat Rev Neurosci. 2000 Oct; 1(1):31-40. Brainard MS, Doupe AJ. PMID: 11252766.
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Interruption of a basal ganglia-forebrain circuit prevents plasticity of learned vocalizations. Nature. 2000 Apr 13; 404(6779):762-6. Brainard MS, Doupe AJ. PMID: 10783889.
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Images in neuroscience. Brain development, V: Experience affects brain development. Am J Psychiatry. 1998 Aug; 155(8):1000. Brainard MS, Knudsen EI. PMID: 9699684.
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Sensitive periods for visual calibration of the auditory space map in the barn owl optic tectum. J Neurosci. 1998 May 15; 18(10):3929-42. Brainard MS, Knudsen EI. PMID: 9570820.
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Newly learned auditory responses mediated by NMDA receptors in the owl inferior colliculus. Science. 1996 Jan 26; 271(5248):525-8. Feldman DE, Brainard MS, Knudsen EI. PMID: 8560271.
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Dynamics of visually guided auditory plasticity in the optic tectum of the barn owl. J Neurophysiol. 1995 Feb; 73(2):595-614. Brainard MS, Knudsen EI. PMID: 7760121.
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Creating a unified representation of visual and auditory space in the brain. Annu Rev Neurosci. 1995; 18:19-43. Knudsen EI, Brainard MS. PMID: 7605060.
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Neural substrates of sound localization. Curr Opin Neurobiol. 1994 Aug; 4(4):557-62. Brainard MS. PMID: 7812145.
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Experience-dependent plasticity in the inferior colliculus: a site for visual calibration of the neural representation of auditory space in the barn owl. J Neurosci. 1993 Nov; 13(11):4589-608. Brainard MS, Knudsen EI. PMID: 8229186.
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Neural derivation of sound source location: resolution of spatial ambiguities in binaural cues. J Acoust Soc Am. 1992 Feb; 91(2):1015-27. Brainard MS, Knudsen EI, Esterly SD. PMID: 1556303.
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Visual instruction of the neural map of auditory space in the developing optic tectum. Science. 1991 Jul 05; 253(5015):85-7. Knudsen EI, Brainard MS. PMID: 2063209.
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Single-channel analysis of four distinct classes of potassium channels in Drosophila muscle. J Neurosci. 1988 Dec; 8(12):4765-79. Zagotta WN, Brainard MS, Aldrich RW. PMID: 3199204.
Michael Brainard earned his undergraduate degree in Biochemistry from Harvard University before pursuing a PhD in Neurobiology at Stanford University.
Dr. Brainard is a Howard Hughes Medical Institute Investigator.
Sooyoon Shin, Postdoctoral Fellow
Paul Jaffe, GSR
Jeffrey Knowles, GSR
Lucas Tian, GSR