Julie Elizabeth Miller

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Journals/Publications

• Medina, C. A., Vargas, E., Munger, S. J., & Miller, J. E. (2022). Vocal changes in a zebra finch model of Parkinson's disease characterized by alpha-synuclein overexpression in the song-dedicated anterior forebrain pathway. PloS one, 17(5), e0265604.
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  Deterioration in the quality of a person's voice and speech is an early marker of Parkinson's disease (PD). In humans, the neural circuit that supports vocal motor control consists of a cortico-basal ganglia-thalamo-cortico loop. The basal ganglia regions, striatum and globus pallidus, in this loop play a role in modulating the acoustic features of vocal behavior such as loudness, pitch, and articulatory rate. In PD, this area is implicated in pathogenesis. In animal models of PD, the accumulation of toxic aggregates containing the neuronal protein alpha-synuclein (αsyn) in the midbrain and striatum result in limb and vocal motor impairments. It has been challenging to study vocal impairments given the lack of well-defined cortico-basal ganglia circuitry for vocalization in rodent models. Furthermore, whether deterioration of voice quality early in PD is a direct result of αsyn-induced neuropathology is not yet known. Here, we take advantage of the well-characterized vocal circuits of the adult male zebra finch songbird to experimentally target a song-dedicated pathway, the anterior forebrain pathway, using an adeno-associated virus expressing the human wild-type αsyn gene, SNCA. We found that overexpression of αsyn in this pathway coincides with higher levels of insoluble, monomeric αsyn compared to control finches. Impairments in song production were also detected along with shorter and poorer quality syllables, which are the most basic unit of song. These vocal changes are similar to the vocal abnormalities observed in individuals with PD.
• Ausra, J., Munger, S. J., Azami, A., Burton, A., Peralta, R., Miller, J. E., & Gutruf, P. (2021). Wireless battery free fully implantable multimodal recording and neuromodulation tools for songbirds. Nature communications, 12(1), 1968.
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  Wireless battery free and fully implantable tools for the interrogation of the central and peripheral nervous system have quantitatively expanded the capabilities to study mechanistic and circuit level behavior in freely moving rodents. The light weight and small footprint of such devices enables full subdermal implantation that results in the capability to perform studies with minimal impact on subject behavior and yields broad application in a range of experimental paradigms. While these advantages have been successfully proven in rodents that move predominantly in 2D, the full potential of a wireless and battery free device can be harnessed with flying species, where interrogation with tethered devices is very difficult or impossible. Here we report on a wireless, battery free and multimodal platform that enables optogenetic stimulation and physiological temperature recording in a highly miniaturized form factor for use in songbirds. The systems are enabled by behavior guided primary antenna design and advanced energy management to ensure stable optogenetic stimulation and thermography throughout 3D experimental arenas. Collectively, these design approaches quantitatively expand the use of wireless subdermally implantable neuromodulation and sensing tools to species previously excluded from in vivo real time experiments.
• Badwal, A., Borgstrom, M., Samlan, R. A., & Miller, J. E. (2020). Middle age, a key time point for changes in birdsong and human voice. Behavioral neuroscience, 134(3), 208-221.
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  Voice changes caused by natural aging and neurodegenerative diseases are prevalent in the aging population and diminish quality of life. Most treatments involve behavioral interventions that target the larynx because of a limited understanding of central brain mechanisms. The songbird offers a unique entry point into studying age-related changes in vocalizations because of a well-characterized neural circuitry for song that shares homology to human vocal control areas. Previously we established a translational dictionary for evaluating acoustic features of birdsong in the context of human voice measurements. In the present study, we conduct extensive analyses of birdsongs from young, middle-aged, and old male zebra finches. Our findings show that birdsongs become louder with age, and changes in periodic energy occur at middle age but are transient; songs appear to stabilize in old birds. Furthermore, faster songs are detected in finches at middle age compared with young and old finches. Vocal disorders in humans emerge at middle age, but the underlying brain pathologies are not well identified. The current findings will motivate future investigations using the songbird model to identify possible brain mechanisms involved in human vocal disorders of aging. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
• So, L. Y., & Miller, J. E. (2020). Social context-dependent singing alters molecular markers of synaptic plasticity signaling in finch basal ganglia Area X. Behavioural brain research, 398, 112955.
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  Vocal communication is a crucial skill required throughout life. However, there is a critical gap in our understanding of the underlying molecular brain mechanisms, thereby motivating our use of the zebra finch songbird model. Adult male zebra finches show differences in neural activity patterns in song-dedicated brain nuclei when they sing in two distinct social contexts: a male singing by himself (undirected, UD) and a male singing to a female (female-directed, FD). In our prior work, we showed that in song-dedicated basal ganglia Area X, protein levels of a N-methyl-D-aspartate receptor subtype 2B (NMDAR2B) increased with more UD song and decreased with more FD song. We hypothesized that molecules downstream of this receptor would show differential protein expression levels in Area X between UD and FD song. Specifically, we investigated calcium/calmodulin dependent protein kinase II beta (CaMKIIB), homer scaffold protein 1 (HOMER1), serine/threonine protein kinase (Akt), and mechanistic target of rapamycin kinase (mTOR) following singing and non-singing states in Area X. We show relationships between social context and protein levels. HOMER1 protein levels decreased with time spent singing FD song, and mTOR protein levels decreased with the amount of and time spent singing FD song. For both HOMER1 and mTOR, there were no differences with the amount of UD song. With time spent singing UD, CaMKIIB protein levels trended in a U-shaped curve whereas Akt protein levels trended down. Both molecules showed no change with FD song. Our results support differential involvement of molecules in synaptic plasticity pathways between UD and FD song behaviors.
• Badwal, A., Miller, J. E., Poertner, J., & Samlan, R. A. (2019).

  Common Terminology and Acoustic Measures for Human Voice and Birdsong

  . Journal of Speech, Language, and Hearing Research, 62(1), 60-69. doi:10.1044/2018_jslhr-s-18-0218
• Badwal, A., Poertner, J., Samlan, R. A., & Miller, J. E. (2018). Common Terminology and Acoustic Measures for Human Voice and Birdsong. Journal of speech, language, and hearing research : JSLHR, 1-10. doi:doi=10.1044/2018_JSLHR-S-18-0218
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  The zebra finch is used as a model to study the neural circuitry of auditory-guided human vocal production. The terminology of birdsong production and acoustic analysis, however, differs from human voice production, making it difficult for voice researchers of either species to navigate the literature from the other. The purpose of this research note is to identify common terminology and measures to better compare information across species.
• So, L. Y., Munger, S. J., & Miller, J. E. (2018). Social context-dependent singing alters molecular markers of dopaminergic and glutamatergic signaling in finch basal ganglia Area X. Behavioural brain research, 360, 103-112. doi:doi: 10.1016/j.bbr.2018.12.004
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  Dopamine (DA) is an important neuromodulator of motor control across species. In zebra finches, DA levels vary in song nucleus Area X depending upon social context. DA levels are high and song output is less variable when a male finch sings to a female (female directed, FD) compared to when he is singing by himself (undirected, UD). DA modulates glutamatergic input onto cortico-striatal synapses in Area X via N-methyl-d-aspartate (NMDA) and DA receptor mechanisms, but the relationship to UD vs. FD song output is unclear. Here, we investigate the expression of molecular markers of dopaminergic and glutamatergic synaptic transmission (tyrosine hydroxylase - TH, alpha-synuclein - α-syn) and plasticity (NMDA 2B receptor - GRIN2B) following singing (UD vs. FD) and non-singing states to understand the molecular mechanisms driving differences in song output. We identified relationships between protein levels for these biomarkers in Area X based on singing state and the amount of song, measured as the number of motifs and time spent singing. UD song amount drove increases in TH, α-syn, and NMDA 2B receptor protein levels. By contrast, the amount of FD song did not alter TH and NMDA 2B receptor expression. Levels of α-syn showed differential expression patterns based on UD vs. FD song, consistent with its role in modulating synaptic transmission. We propose a molecular pathway model to explain how social context and amount of song are important drivers of molecular changes required for synaptic transmission and plasticity.
• Miller, J. E. (2015). Reduced vocal variability in a zebra finch model of dopamine depletion: implications for Parkinson disease.. Physiological Reports, 3(11). doi:10.14814/phy2.12599
• Grant, L. M., Richter, F., Miller, J., White, S., Fox, C., Chesselet, M., & Ciucci, M. (2014). Vocalization deficits in mice over-expressing alpha-synuclein, a model of pre-manifest Parkinson's disease.. Behav Neurosci, 128, 110-121.
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  PMID: 24773432
• Hilliard, A. T., Miller, J., Horvath, S., & White, S. (2012). Distinct Neurogenomic States in Basal Ganglia Subregions Relate Differently to Singing Behavior in Songbirds. PloS Comput Biol, 8(11), e1002773.
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  PMID: 23144607
• Hilliard, A., Miller, J., Fraley, E., Horvath, S., & White, S. (2012). Molecular Microcircuitry Underlies Functional Specification in a Basal Ganglia Circuit Dedicated to Vocal Learning. Neuron, 73, 537-552.
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  PMID: 22325205

Presentations

• Miller, J. E. (2023). Vocalizations and the Aging Brain. . invited seminar, Dept of Biology, City College of New York.
• Miller, J. E. (2023, August). Alpha-Synuclein Driven Vocal Dysfunction in Parkinson's Disease: insights from animal models.. invited seminar, Univ. Arizona Parkinson's Disease Group.
• Miller, J. E. (2023, July). Alpha-Synuclein Driven Vocal Dysfunction in Parkinson's Disease: insights from animal models.. invited seminar, Department of Communication Sciences and Disorders, University of Wisconsin-Madison.
• Miller, J. E. (2023, March). Neural Circuitry Investigations in a Finch Model of Parkinsonian Vocal Deficits. . invited seminar, Univ. Arizona Physiological Sciences Electrophysiology Group.
• Garcia, E., & Miller, J. E. (2022). Acoustic Alterations in Aging Birdsongs as a Model for Humans.. UROC Minimizing Health Disparities Summer Program.
• Gordon, M., & Miller, J. E. (2021). Age-related changes in birdsong: an adult male zebra finch longitudinal study,. Border Latino & American Indian Summer Exposure to Research (BLAISER) Summer Program.
• Ibrahim, N., Munger, S. J., Ausra, J., Azami, A., Burton, A., Peralta, R., Gutruf, P., & Miller, J. E. (2020, November). Effects of Optogenetic Manipulation on Song in a Zebra Finch Model.. Annual Biomedical Research Conference for Minority Students (ABRCMS)Annual Biomedical Research Conference for Minority Students (ABRCMS).
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  Undergraduate MARC student Naya Ibrahim won a cash prize for her oral presentation in the virtual format.
• Miller, J. E. (2019, August/Summer). What Birdsong Can Teach Us About How We Communicate. Arizona Senior Academy Village. Academy Village Senior Living Faculty Lecture Series.
• Miller, J. E. (2019, February 2019). What Birdsong Can Teach Us About How We Communicate. College of Science, Science. College of Science, Science Café Public Lecture Series. Magpies Pizza on 4th Ave.
• Miller, J. E. (2018, November/Fall). Voice, Aging and Parkinson's Disease. University of Arizona, Neuroscience Ph.D. Program Datablitz.
• Miller, J. E. (2016, August/Summer). Molecular Substrates for Vocal Plasticity in the Zebra Finch.. Southwest Brain, Cognition and Vocal Behavior Meeting..
• Miller, J. E. (2016, December/Fall). Neuromolecular Mechanisms for Speech Motor Control.. Arizona State University, Dept. of Speech and Hearing Sciences Seminar Series..
• Miller, J. E. (2016, March/Spring). The Role of the Basal Ganglia in Neural Control of Speech (and Language).. University of Arizona Cognitive Science Seminar Series..
• Miller, J. E. (2016, May/Spring). Journal Club Article Presentation. University of Arizona Health Sciences Center Neurology Journal Club.
• Miller, J. E. (2016, September/Fall). Neuromolecular Mechanisms for Speech Motor Control.. University of Arizona Speech,Lang, Hearing Sciences Colloquium Series.
• Miller, J. E. (2015, January). Goals of the Miller Laboratory. Data Blitz Presentation for Ph.D. in Neuroscience Recruitment.
• Miller, J. E. (2014, February). Understanding Human Motor Systems By Studying Animal Models. ‘Conversations with Faculty’ series Univ. Arizona Undergraduate Biology ProgramUniv. Arizona, Undergraduate Biology Program.
• Miller, J. E. (2014, January). Univ. Arizona, Ph.D. Program in Neuroscience Data Blitz. Univ. Arizona, Ph.D. Program in Neuroscience Data Blitz. Tucson, AZ: Tucson Botanical Gardens.
• Miller, J. E. (2014, May). Genetic Targets for Vocal Function & Dysfunction.. Univ. Arizona, Speech, Language and Hearing Sciences Colloquium Series.
• Miller, J. E. (2014, May). The Songbird Model: A Window into Understanding Neural & Peripheral Mechanisms Supporting Voice and Speech. Univ. Arizona, University Animal Care & state-wide AALAS meeting.
• Miller, J. E. (2013, August). The Songbird Model: A Window into Understanding Neural and Peripheral Mechanisms Supporting Voice and Speech. American Speech-Language-Hearing Association ConferenceChicago, IL.

Poster Presentations

• Brian, D. R., Gabriel, H., Reed, B., Miller, J. E., & Cowen, S. L. (2023, November). Alpha-synuclein overexpression in the basal ganglia vocal nucleus Area X alters waveform patterns in a zebra finch model of Parkinsonian vocal deficits. . Society for Neuroscience.
• Higgins, C. M., & Miller, J. E. (2023, September). Altered Basal Ganglia Gene Networks for Vocal Function in Normative Aging and Parkinson’s Disease.. Arizona Alzheimer’s Consortium Conference.
• Gordon, M. L., & Miller, J. E. (2022).

  Age-related changes in birdsong: an adult male zebra finch longitudinal study

   

  . Border Latino & American Indian Summer Exposure to Research (BLAISER) program, University of Arizona UROC Conference.
• Medina, C. A., Munger, S. J., Corenblum, M., Eckhardt, J., Madhavan, L., & Miller, J. E. (2021). An analysis of vocalization-associated molecular pathways and gene networks within the basal ganglia of mouse and finch Parkinson’s disease models. . Society for Neuroscience Annual Meeting.
• Medina, C. A., Munger, S., Corenblum, M., Eckhardt, J., Madhavan, L., & Miller, J. E. (2021). An analysis of vocalization-associated molecular pathways and gene networks within the basal ganglia of mouse and finch Parkinson’s disease models.. Society for Neuroscience Annual Meeting-Virtual.
• Vargas, E., Medina, C. A., Munger, S. J., & Miller, J. E. (2020, August). Alpha-synuclein in the zebra finch brain: Molecular and behavioral validation of a Parkinson’s disease model.. Border Latino & American Indian Summer Exposure to Research (BLAISER) Program. University of Arizona.
• Vargas, E., Medina, C. A., Munger, S. J., & Miller, J. E. (2020, January). Alpha-synuclein Overexpression Leads to Reduced Singing in a Zebra Finch Model of Parkinson’s Disease.. Undergraduate Biology Research Program (UBRP) Winter Conference. University of Arizona.
• Badwal, A., Medina, C. A., Munger, S. J., & Miller, J. E. (2019, August/Summer). An Alpha-synuclein Overexpression Model of Vocal Symptoms in Parkinson’s Disease. Microscopy Society of America Conference. Portland, Oregon.
  More info

  doi:10.1017/S1431927619007025, in Microsc. Microanal. 25 (Suppl 2)
• Badwal, A., Samlan, R. A., & Miller, J. E. (2019, May/Spring). Birdsong as a Model for Aging Voice. UA NSCS Honors Theses Poster Presentations. University of Arizona.
• Ibrahim, N., Vargas, E., Medina, C. A., Munger, S. J., & Miller, J. E. (2019, November/Fall). Effects of Alpha-synuclein Overexpression on Time Spent Singing in a Zebra Finch Model of Parkinson’s Disease.. Annual Biomedical Research Conference for Minority Students (ABRCMS). Anaheim, CA.
• Munger, S. J., Medina, C. A., So, L. Y., Church, K. B., Ritter, J. L., & Miller, J. E. (2016, November/Fall). Role of Alpha-synuclein in Area X of Adult Male Zebra Finches: implications for acoustic variability in birdsong.. Society for Neuroscience. San Diego, CA: Society for Neuroscience.
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  Author order: S.J. Munger, C.A. Medina, L.Y. So, K.B. Church, J.L. Ritter, J.E. Miller.
• So, L. Y., Munger, S. J., & Miller, J. E. (2016, November/Fall). Behavioral Regulation of Dopamine Biomarkers in Area X of Adult Male Zebra Finch Songbirds.. Society for Neuroscience. San Diego, CA: Society for Neuroscience.
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  Author order: L.Y. So, S.J. Munger, J.E. Miller.
• Hafzalla, G., White, S., & Miller, J. (2014, Spring). Consequences of Experimental Dopamine Depletion in the Songbird Basal Ganglia. 11th International Congress of Neuroethology. Sapporo Japan.
• Lee, D., Hafzalla, G., Burkett, Z., Miller, J., & White, S. (2012, Fall). Characterization of Dopamine Levels and Vocal Motor Deficits in Zebra Finch After Injection of 6-Hydroxydopamine into Area X. UCLA Undergraduate Poster Day.

Creative Productions

• Miller, J. E. (2019. How Birdsong Can Help Us Understand Human Speech.. Arizona Science National Public Interview, episode 163..
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  https://radio.azpm.org/p/radio-azscience/2019/1/10/144130-episode-163-how-birdsong-can-help-us-understand-human-speech/