Growth and splitting of neural sequences in songbird vocal development

Neural sequences are a fundamental feature of brain dynamics underlying diverse behaviours, but the mechanisms by which they develop during learning remain unknown. Songbirds learn vocalizations composed of syllables; in adult birds, each syllable is produced by a different sequence of action potential bursts in the premotor cortical area HVC. Here we carried out recordings of large populations of HVC neurons in singing juvenile birds throughout learning to examine the emergence of neural sequences. Early in vocal development, HVC neurons begin producing rhythmic bursts, temporally locked to a prototype syllable. Different neurons are active at different latencies relative to syllable onset to form a continuous sequence. Through development, as new syllables emerge from the prototype syllable, initially highly overlapping burst sequences become increasingly distinct. We propose a mechanistic model in which multiple neural sequences can emerge from the growth and splitting of a commo n precursor sequence.National Institutes of Health (U.S.) (Grant R01DC009183)National Science Foundation (U.S.) (Grant DGE-114747

Building a state space for song learning

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2018.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 159-177).Song learning circuitry is thought to operate using a unique representation of each moment within each song syllable. Distinct timestamps for each moment in the song have been observed in the premotor cortical nucleus HVC, where neurons burst in sparse sequences. However, such sparse sequences are not present in very young birds, which sing highly variable syllables of random lengths. Furthermore, young birds learn by imitating a tutor song, and it was previously unclear precisely how the experience of hearing a tutor might shape auditory, motor, and evaluation pathways in the songbird brain. My thesis presents a framework for how these pathways may assemble during early learning, using simple neural mechanisms. I start with a neural network model for how premotor sequences may grow and split. This model predicts that the sequence-generating nucleus HVC would receive rhythmically patterned training inputs. I found such a signal when I recorded neurons that project to HVC. When juvenile birds sing, these neurons burst at the beginning of each syllable, and when the birds listen to a tutor, neurons burst at the rhythm of the tutor's song. Bursts marking the beginning of every tutor syllable could seed chains of sequential activity in HVC that could be used to generate the bird's own song imitation. I next used functional calcium imaging to characterize HVC sequences before and after tutor exposure. Analysis of these datasets led us to develop a new method for unsupervised detection of neural sequences. Using this method, I was able to observe neural sequences even prior to tutor exposure. Some of these sequences could be tracked as new syllables emerged after tutor exposure, and some sequences appeared to become coupled to the new syllables. In light of my new data, I expand on previous models of song learning to form a detailed hypothesis for how simple neural processes may perform song learning from start to finish.by Emily Lambert Mackevicius.Ph. D

In Vivo Recording of Single-Unit Activity during Singing in Zebra Finches

The zebra finch is an important model for investigating the neural mechanisms that underlie vocal production and learning. Previous anatomical and gene expression studies have identified an interconnected set of brain areas in this organism that are important for singing. To advance our understanding of how these various brain areas act together to learn and produce a highly stereotyped song, it is necessary to record the activity of individual neurons during singing. Here, we present a protocol for recording single-unit activity in freely moving zebra finches during singing using a miniature, motorized microdrive. It includes procedures for both the microdrive implant surgery and the electrophysiological recordings. There are several advantages of this technique: (1) high-impedance electrodes can be used in the microdrive to obtain well-isolated single units; (2) a motorized microdrive is used to remotely control the electrode position, allowing neurons to be isolated without handling the bird, and (3) a lateral positioner is used to move electrodes into fresh tissue before each penetration, allowing recordings from well-isolated neurons over the course of several weeks. We also describe the application of the antidromic stimulation and the spike collision test to identify neurons based on the axonal projection patterns.National Institutes of Health (U.S.) (Grant R01DC009183)National Institutes of Health (U.S.) (Grant R01MH067105)Nakajima FoundationSchoemaker FellowshipUnited States. Dept. of Defense. National Defense Science & Engineering Graduate Fellowship Progra

An avian cortical circuit for chunking tutor song syllables into simple vocal-motor units

© 2020, The Author(s). How are brain circuits constructed to achieve complex goals? The brains of young songbirds develop motor circuits that achieve the goal of imitating a specific tutor song to which they are exposed. Here, we set out to examine how song-generating circuits may be influenced early in song learning by a cortical region (NIf) at the interface between auditory and motor systems. Single-unit recordings reveal that, during juvenile babbling, NIf neurons burst at syllable onsets, with some neurons exhibiting selectivity for particular emerging syllable types. When juvenile birds listen to their tutor, NIf neurons are also activated at tutor syllable onsets, and are often selective for particular syllable types. We examine a simple computational model in which tutor exposure imprints the correct number of syllable patterns as ensembles in an interconnected NIf network. These ensembles are then reactivated during singing to train a set of syllable sequences in the motor network

Unsupervised discovery of temporal sequences in high-dimensional datasets, with applications to neuroscience

Identifying low-dimensional features that describe large-scale neural recordings is a major challenge in neuroscience. Repeated temporal patterns (sequences) are thought to be a salient feature of neural dynamics, but are not succinctly captured by traditional dimensionality reduction techniques. Here, we describe a software toolbox-called seqNMF-with new methods for extracting informative, non-redundant, sequences from high-dimensional neural data, testing the significance of these extracted patterns, and assessing the prevalence of sequential structure in data. We test these methods on simulated data under multiple noise conditions, and on several real neural and behavioral datas. In hippocampal data, seqNMF identifies neural sequences that match those calculated manually by reference to behavioral events. In songbird data, seqNMF discovers neural sequences in untutored birds that lack stereotyped songs. Thus, by identifying temporal structure directly from neural data, seqNMF enables dissection of complex neural circuits without relying on temporal references from stimuli or behavioral outputs.NIH Office of the Director (Grant 5T32EB019940-03)National Institute on Deafness and Other Communication Disorders (Grant R01-DC009183)National Institute of Neurological Disorders and Stroke (Grant U19-NS104648)National Institute of Mental Health (Grant R25 MH062204