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Secondary biochemical messengers sustain persistent neural activity in the brainstem.
My first postdoc project focused on a simple question: how do neurons change their activity over minutes, or even hours? We used a new suite of optical tools that were established by two previous postdocs in the lab, Andrew Lutas and Stephen Zhang, to show that cAMP (a ubiquitous second messenger that is produced after activation of many GPCRS) is directly coupled to activity in the brainstem. We thought this was interesting, because cAMP can remain elevated in a cell for long periods of time (minutes to hours) before being degraded, providing a means by which transient ligand binding can change neural circuit activity for long periods of time. We think similar mechanisms could be important for long-lasting brain states such as chronic pain and hunger. Singh Alvarado J*, Lutas A*, Madara J, Isaac J, Lommer, C et al. Transient cAMP production drives rapid and sustained spiking in brainstem parabrachial nucleus neurons to suppress feeding. Neuron. 2024 |
Neural dynamics underlying birdsong practice and performance
In this paper, we use the songbird to tackle two questions: 1) How are complex behaviors such as vocalizations controlled by the brain? 2) How does social environment shape vocalizations?
One brain region, the striatum, is at the center of many theories of speech learning and performance. prism-based miniscope imaging to image striatal neurons as birds sang alone (practice) or in the company of a female (performance). We uncovered a role for the striatum in shaping the structure of vocalizations during practice, allowing the bird to explore vocal space. When singing to a female, adrenaline rushes in and effectively inactivates the striatum, allowing the bird to perform reliable, stereotyped songs that are highly valued by their target audience.
Singh Alvarado J, Goffinet J, Michael V, Liberti W, et al. Neural dynamics underlying birdsong practice and performance. Nature. 2021
In this paper, we use the songbird to tackle two questions: 1) How are complex behaviors such as vocalizations controlled by the brain? 2) How does social environment shape vocalizations?
One brain region, the striatum, is at the center of many theories of speech learning and performance. prism-based miniscope imaging to image striatal neurons as birds sang alone (practice) or in the company of a female (performance). We uncovered a role for the striatum in shaping the structure of vocalizations during practice, allowing the bird to explore vocal space. When singing to a female, adrenaline rushes in and effectively inactivates the striatum, allowing the bird to perform reliable, stereotyped songs that are highly valued by their target audience.
Singh Alvarado J, Goffinet J, Michael V, Liberti W, et al. Neural dynamics underlying birdsong practice and performance. Nature. 2021
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Building Opportunities and Overtures in Science and Technology: Establishing an Early Intervention, Multi-level, Continuous STEM Pathway Program
STEM outreach programs are an important way to reduce racial inequities in science by preparing underrepresented students for a career in STEM. This article describes a sustainable, community-based, longitudinal (5+ year track) program that can be implemented at most universities. The program is founded on the principle of citizen science and near-peer mentorship. Garcia J, Gibson R, Breslav A, Singh Alvarado J, Seas A, Maduka A, et al. Building Opportunities and Overtures in Science and Technology: Establishing an Early Intervention, Multi-level, Continuous STEM Pathway Program. Journal of STEM Outreach. 2021. |
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MIN1PIPE: A Miniscope 1-Photon-Based Calcium Imaging Signal Extraction Pipeline
Miniaturized microscopes have opened new vistas for understanding neural activity in behaving animals. One important challenge of this technique is how noisy it can be - animals are moving and optics are compact. This paper describes new and improved methods for extracting reliable neuronal signals from 1-photon miniaturized microscopy data. Lu J, Li C, Singh Alvarado J, et al. MIN1PIPE: A Miniscope 1-Photon-Based Calcium Imaging Signal Extraction Pipeline. Cell Rep. 2018. |
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Focal expression of mutant huntingtin in the songbird basal ganglia disrupts cortico-basal ganglia networks and vocal sequences
Neurological diseases are often studied at two extremes: molecules and behavior. In between these two levels is the activity of neural circuits. Songbird brains are highly specialized to produce a single behavior: song, allowing us to more effectively bridge the gap between molecular components and behavior. This paper explores how a key mutation in Huntington's disease impacts birdsong and its underlying neural circuitry. We demonstrate that song becomes highly disorganized, and we uncover the neural circuit components that are responsible for these pathological changes. Tanaka M, Singh Alvarado J, Murugan M, and Mooney R. Focal expression of mutant huntingtin in the songbird basal ganglia disrupts cortico-basal ganglia networks and vocal sequences. Proc. Natl. Acad. Sci. USA. 2016 March 07. doi:10.1073/pnas.152375411. |
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Astrocytes refine cortical connectivity at dendritic spines
Risher WC, Patel S, Kim IH, Uezu A, Bhagat S, Wilton DK, Pilaz LJ, Singh Alvarado J, Calhan OY, Silver DL, Stevens B, Soderling SH, and Eroglu C. Astrocytes refine cortical connectivity at dendritic spines. Luo L, ed. eLife. 2014;3:e04047. |
Rapid Golgi Analysis Method for Efficient and Unbiased Classification of Dendritic Spines
Risher WC, Ustunkaya T, Singh Alvarado J, Eroglu C. Rapid Golgi Analysis Method for Efficient and Unbiased Classification of Dendritic Spines. Dunaevsky A, ed. PLoS ONE. 2014;9(9):e107591.
