About

David J. Perkel is a professor in the Department of Biology at the University of Washington. His research focuses on understanding the neural mechanisms underlying song learning and production in songbirds, using electrophysiological, anatomical, and behavioral approaches. He investigates the neural circuits involved in vocal learning, particularly the motor pathway originating from the forebrain nucleus HVC and projecting to the syrinx muscles, as well as the anterior forebrain pathway (AFP) that is essential for vocal learning but not for the production of learned song. His work explores the structure and function of these circuits, their evolutionary origins, and how seasonal changes influence song behavior. Perkel's long-term goal is to elucidate how neurons, synapses, and circuits mediate song learning and production. His research includes studying pattern generation in the motor pathway, the role of the AFP in vocal learning, and the neural basis of vocal plasticity. He has contributed to understanding basal ganglia circuits in songbirds, the modulation of neural activity by neurotransmitters, and the mechanisms of neural plasticity related to song behavior. His work provides insights into broader neural processes of learning, motor control, and neurobiology of communication.

Research topics

• Neuroscience
• Biology
• Artificial Intelligence
• Computer Science
• Anatomy
• Psychology
• Computer vision
• Chemistry

Selected publications

• Vocal Fold Atrophy in an Alzheimer's Disease Rat Model

  The Laryngoscope · 2026-02-22

  articleOpen access

  OBJECTIVES: Advanced Alzheimer's disease (AD) is associated with impaired voice, oropharyngeal dysphagia, and aspiration pneumonia. Vocal fold atrophy is hypothesized to contribute to these changes. While vocal fold atrophy is observed in AD, advanced age is co-prevalent and a confounding variable. The apolipoprotein E4 knock-in (ApoE4-KI) rat model is commonly used to study cognitive and motor changes in AD. This study aims to compare vocal fold atrophy in adult AD rats vs. age-matched controls. METHODS: Vocal folds were visualized endoscopically in 4-month ApoE4-KI rats (n = 12) and age-matched controls (n = 8) following anesthesia. The thyroarytenoid (TA) muscle was collected for histology. Vocal fold bowing index (BI) was calculated from endoscopic still images by two blinded reviewers using digital software. Digital myofiber analysis was used to calculate TA myofiber average cross-sectional area (CSA) and minimum Feret diameter (MFD). RESULTS: ), 586.3 ± 76.9 vs. 435.8 ± 49.4, difference 150.5 with 95% CI 91.2-209.9, p < 0.01; MFD (μm), 23.0 ± 1.1 vs. 19.8 ± 1.3, difference 3.2 with 95% CI 2.0-4.4, p < 0.01). CONCLUSION: Non-aged AD rats had significantly higher BI and TA myofiber size than controls. BI was strongly correlated with histologic metrics. These findings suggest that AD may lead to greater vocal fold atrophy in non-aged animals. Additional studies are needed to determine the mechanism(s) for vocal fold atrophy in this model. LEVEL OF EVIDENCE: N/A.

  PublisherOA PDFDOI

• Effects of Aging on Superior Laryngeal Sensory and Motor Function in a Rat Model

  Otolaryngology · 2026-01-26

  article

  OBJECTIVE: Aging is a risk factor for diminished laryngeal sensation, dysphagia, and aspiration events; however, the mechanisms underlying age-related swallow dysfunction are not well understood. Some of these changes are thought to be mediated through superior laryngeal nerve (SLN) dysfunction. The purpose of this study was to measure the effects of aging on SLN motor and sensory function in a rat model. STUDY DESIGN: Animal study. SETTING: Tertiary-care center. METHODS: Evoked response studies were performed by SLN stimulation. Outcome measures included compound motor (CMAP) and sensory nerve action potential (SNAP) measurements recorded from the cricothyroid muscle and the internal branch of the SLN, respectively. Swallow force measurements were recorded by stimulating the SLN and quantifying the hyoid elevation force. Additionally, force and frequency of electrically and tactile-stimulated swallow reflex were analyzed. These measures were collected in adult Sprague-Dawley rats aged 4, 18, and 24 months. RESULTS: Compared to non-aged rats, advanced age was associated with significantly longer SNAP latency and total duration with a mean difference (95% CI) of 1.23 milliseconds (1.06-1.40) and 2.24 milliseconds (1.89-2.59), respectively. CMAP latency and total duration were also increased by 0.27 milliseconds (0.23-0.31) and 1.5 milliseconds (1.14-1.87), respectively. Advanced age was associated with decreased electrical and tactile-stimulated swallow frequency with a mean difference of 3.3 swallows/10 seconds (95% CI 1.1-5.5) and 2.1 swallows/10 seconds (95% CI 0.71-3.5), respectively. CONCLUSION: Advanced age was associated with longer SNAP and CMAP duration and decreased swallow frequency. The results suggest delayed nerve conduction as a potential mechanism for age-related swallow dysfunction in our rat model. Our work has implications in humans with the hopes for developing targeted therapies for age-related swallow dysfunction. LEVEL OF EVIDENCE: N/A.

  PublisherDOI

• Model-Based Inference of Electrode Distance and Neuronal Density from Measured Detection Thresholds in Cochlear Implant Listeners

  Journal of the Association for Research in Otolaryngology · 2025-03-06 · 1 citations

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Recordings of Superior Laryngeal Nerve Sensory Nerve Action Potentials in a Rat Model

  The Laryngoscope · 2024-08-12 · 3 citations

  article

  OBJECTIVE: Superior laryngeal nerve (SLN) function is critical to laryngeal sensation. Sensory dysfunction in the larynx, mediated through the internal branch of the superior laryngeal nerve (iSLN), is thought to occur with aging and neurodegenerative disease. However, objective analysis of iSLN neurophysiology is difficult due to its anatomic location and small diameter. This study measures sensory nerve action potentials (SNAP) from the iSLN in a rat model. METHODS: SNAP data were obtained from two adult rat strains (Sprague-Dawley, SD and Fischer 344 × Brown Norway F1 Hybrid rats, FBN). Evoked responses were obtained by stimulating the main trunk of the SLN and recording the response using a 160-μm cuff electrode placed around the iSLN. SNAP were averaged from 10 stimulations. Laryngeal adductor reflex (LAR) threshold measurements were obtained with stimulation of the iSLN and direct laryngoscopy. The sections of the iSLN were obtained for histologic analysis. RESULTS: SLN-evoked responses were successfully obtained in 18 hemi-laryngeal preparations (SD n = 13 and FBN n = 5) with corresponding LAR threshold measurements. Mean(±SD) SNAP latency, total duration, amplitude, negative durations, and intensity were 2.28 ms (±0.56), 2.13 ms (±0.70), 879 μV (±535), and 0.69 mA (±0.25), respectively. SLN stimulation threshold to elicit an LAR was of 0.84 mA (±0.31). CONCLUSION: It is feasible to record evoked SLN responses in two adult rat strains. This work may lead to a tractable animal model for objective measurements of SLN neurophysiology with various disease states. LEVEL OF EVIDENCE: NA Laryngoscope, 134:5028-5033, 2024.

  PublisherDOI

• Dynamics of odor-source localization: Insights from real-time odor plume recordings and head-motion tracking in freely moving mice

  PLoS ONE · 2024-09-26 · 6 citations

  articleOpen access

  Animals navigating turbulent odor plumes exhibit a rich variety of behaviors, and employ efficient strategies to locate odor sources. A growing body of literature has started to probe this complex task of localizing airborne odor sources in walking mammals to further our understanding of neural encoding and decoding of naturalistic sensory stimuli. However, correlating the intermittent olfactory information with behavior has remained a long-standing challenge due to the stochastic nature of the odor stimulus. We recently reported a method to record real-time olfactory information available to freely moving mice during odor-guided navigation, hence overcoming that challenge. Here we combine our odor-recording method with head-motion tracking to establish correlations between plume encounters and head movements. We show that mice exhibit robust head-pitch motions in the 5-14Hz range during an odor-guided navigation task, and that these head motions are modulated by plume encounters. Furthermore, mice reduce their angles with respect to the source upon plume contact. Head motions may thus be an important part of the sensorimotor behavioral repertoire during naturalistic odor-source localization.

  PublisherDOI

• Adult neurogenesis is necessary for functional regeneration of a forebrain neural circuit

  Proceedings of the National Academy of Sciences · 2024-07-05 · 3 citations

  articleOpen accessSenior author

  In adult songbirds, new neurons are born in large numbers in the proliferative ventricular zone in the telencephalon and migrate to the adjacent song control region HVC (acronym used as proper name) [A. Reiner et al. , J. Comp. Neurol. 473 , 377–414 (2004)]. Many of these new neurons send long axonal projections to the robust nucleus of the arcopallium (RA). The HVC–RA circuit is essential for producing stereotyped learned song. The function of adult neurogenesis in this circuit has not been clear. A previous study suggested that it is important for the production of well-structured songs [R. E. Cohen, M. Macedo-Lima, K. E. Miller, E. A. Brenowitz, J. Neurosci. 36 , 8947–8956 (2016)]. We tested this hypothesis by infusing the neuroblast migration inhibitor cyclopamine into HVC of male Gambel’s white-crowned sparrows ( Zonotrichia leucophrys gambelii ) to block seasonal regeneration of the HVC–RA circuit. Decreasing the number of new neurons in HVC prevented both the increase in spontaneous electrical activity of RA neurons and the improved structure of songs that would normally occur as sparrows enter breeding condition. These results show that the incorporation of new neurons into the adult HVC is necessary for the recovery of both electrical activity and song behavior in breeding birds and demonstrate the value of the bird song system as a model for investigating adult neurogenesis at the level of long projection neural circuits.

  PublisherOA PDFDOI

• Mechanistic Hypotheses for Proprioceptive Sensing Within the Avian Lumbosacral Spinal Cord

  Integrative and Comparative Biology · 2023-06-02 · 5 citations

  articleOpen accessSenior author

  Animals need to accurately sense changes in their body position to perform complex movements. It is increasingly clear that the vertebrate central nervous system contains a variety of cells capable of detecting body motion, in addition to the comparatively well-understood mechanosensory cells of the vestibular system and the peripheral proprioceptors. One such intriguing system is the lower spinal cord and column in birds, also known as the avian lumbosacral organ (LSO), which is thought to act as a set of balance sensors that allow birds to detect body movements separately from head movements detected by the vestibular system. Here, we take what is known about proprioceptive, mechanosensory spinal neurons in other vertebrates to explore hypotheses for how the LSO might sense mechanical information related to movement. Although the LSO is found only in birds, recent immunohistochemical studies of the avian LSO have hinted at similarities between cells in the LSO and the known spinal proprioceptors in other vertebrates. In addition to describing possible connections between avian spinal anatomy and recent findings on spinal proprioception as well as sensory and sensorimotor spinal networks, we also present some new data that suggest a role for sensory afferent peptides in LSO function. Thus, this perspective articulates a set of testable ideas on mechanisms of LSO function grounded in the emerging spinal proprioception scientific literature.

  PublisherOA PDFDOI

• Dynamics of odor-source localization: Insights from real-time odor plume recordings and head-motion tracking in freely moving mice

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-11-13 · 4 citations

  preprintOpen access

  Animals navigating turbulent odor plumes exhibit a rich variety of behaviors, and employ efficient strategies to locate odor sources. A growing body of literature has started to probe this complex task of localizing airborne odor sources in walking mammals to further our understanding of neural encoding and decoding of naturalistic sensory stimuli. However, correlating the intermittent olfactory information with behavior has remained a long-standing challenge due to the stochastic nature of the odor stimulus. We recently reported a method to record real-time olfactory information available to freely moving mice during odor-guided navigation, hence overcoming that challenge. Here we combine our odor-recording method with head-motion tracking to establish correlations between plume encounters and head movements. We show that mice exhibit robust head-pitch motions in the 5-14Hz range during an odor-guided navigation task, and that these head motions are modulated by plume encounters. Furthermore, mice reduce their angles with respect to the source upon plume contact. Head motions may thus be an important part of the sensorimotor behavioral repertoire during naturalistic odor-source localization.

  PublisherOA PDFDOI

• Molecular markers of mechanosensation in glycinergic neurons in the avian lumbosacral spinal cord

  bioRxiv (Cold Spring Harbor Laboratory) · 2022-01-28 · 1 citations

  preprintOpen accessSenior author

  Abstract Birds are exceptionally adept at controlling their body position. For example, they can coordinate rapid movements of their body while stabilizing their head. Intriguingly, this ability may rely in part on a mechanosensory organ in the avian lower spinal cord called the lumbosacral organ (LSO). However, molecular mechanotransduction mechanisms have not been identified in the avian spinal cord. Here, we report the presence of glycinergic neurons in the LSO that exhibit immunoreactivity for myosin7a and epsin, molecules essential for function and maintenance of hair cells in the inner ear. Specifically, we find glycinergic cell bodies near the central canal and processes that extend laterally to the accessory lobes and spinal ligaments. These LSO neurons are reminiscent of glycinergic neurons in a recently-described lateral spinal proprioceptive organ in zebrafish that detects spinal bending. The avian LSO, however, is located inside a series of fused vertebrae called the synsacrum, which constrains spinal bending. We suggest the LSO may be a modification and elaboration of a pre-existing mechanosensory spinal network in vertebrates. A mechanistic understanding of its function may be an important clue to understanding the evolution and development of avian locomotion.

  PublisherOA PDFDOI

• MULTIVALVULAR ABSCESSES IN A PATIENT WITH CORYNEBACTERERIUM STRIATUM BACTEREMIA AND UNDIAGNOSED THYMOMA

  Journal of the American College of Cardiology · 2022-03-01

  articleSenior author
  PublisherDOI

Recent grants

• NIH Grant R01NS021376

  NIH · $50k · 1986

• NIH Grant R01MH066128

  NIH · $2.6M · 2014

• NIH Grant R03DC002477

  NIH · $58k · 1996

• Auditory Neuroscience Training Program

  NIH · $8.2M · 2002–2027

• Mechanisms of adult forebrain neural circuit regeneration

  NIH · $2.8M · 2018–2024

Frequent coauthors

• Ann B. Butler

  15 shared

• Arthur Leblois

  Université de Bordeaux

  13 shared

• Eliot A. Brenowitz

  University of Washington

  13 shared

• Erich D. Jarvis

  Rockefeller University

  11 shared

• Kimberly E. Miller

  University of Washington

  10 shared

• Samuel D. Gale

  Allen Institute

  9 shared

• Roger A. Nicoll

  University of California, San Francisco

  9 shared

• Anton Reiner

  University of Tennessee Health Science Center

  9 shared

Education

• B.A.

  Harvard University

  1984

• Ph.D.

  University of California, San Francisco

  1992