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Molecular Mechanisms of Vocal Learning

Research Summary

Erich Jarvis investigates the neurobiology of learned vocal communication in the rare group of animals that have this ability, as a model for the study of how the brain generates, perceives, and learns complex behaviors, such as spoken language. His specific quest is to determine the molecular mechanisms that construct, modify, and maintain neural circuits for vocal learning and then engineer brain circuits to repair and enhance those behaviors.

Vocal learning is the ability to imitate or modify vocalizations. Studying the mechanisms requires that we compare the genes, vocal behavior, and associated brain pathways of the few rare groups that have vocal learning with the vast majority of species that do not. Vocal learners include at least three groups of distantly related mammals (humans, cetaceans, and bats) and three groups of distantly related birds (parrots, hummingbirds, and songbirds). Remarkably, although vocal learning groups are distantly related to each other, they share a similar organization of brain pathways for vocal communication: a premotor pathway necessary for vocal learning and a motor pathway necessary for production of learned vocalizations. These forebrain pathways are not found in vocal nonlearners, yet vocal learners and nonlearners possess similar brain pathways for learning and production of other motor behaviors. We hypothesize that the fundamental distinctions between vocal learners and nonlearners are genetic differences that control the connection of forebrain motor-learning pathways onto brainstem motor neurons that normally control production of innate vocalizations. Once a vocal-learning circuit is established, we believe that it employs the same molecular mechanisms as the motor pathway circuits that we found are adjacent to vocal learning circuits.

Constructing Vocal-Learning Circuits
To test this hypothesis, we seek to discover the necessary and sufficient molecules that construct the circuits that make the critical differences between vocal-learning and vocal-nonlearning animals. Toward this end, we have found that the vocal-learning brain systems in birds have gene expression parallels with brain pathways for speech production in humans. In particular, the avian posterior vocal pathway has specialized expression of specific genes similar to the human laryngeal motor cortex. Similarly to the avian posterior vocal pathway for learned song, the human laryngeal motor cortex sends direct projections to brainstem motor neurons involved in the production of learned song and speech. These direct projections are yet to be seen in vocal-nonlearning birds or mammals, including nonhuman primates. The avian anterior forebrain vocal pathway has specializations similar to those of cortical-basal-ganglia-thalamic regions involved in higher functions of speech production and learning. The genes identified are enriched for functions in neural connectivity. To test for the functional role of these genes, we have embarked on a study to manipulate them in the brains of both vocal-learning and -nonlearning animals.

Maintaining Vocal-Learning Circuits
When a vocal-learning circuit is formed during development, the circuit must be modified and maintained in order for an individual to learn and control its learned motor behavior. We believe that these processes involve both constitutive and activity-dependent genes. We have identified a cascade of gene regulation involving approximately 10 percent of the transcribed genome (>2,700 genes) that is activated by production of learned vocalizations. We call this activation motor-driven gene expression. We have developed and utilized computational inference algorithms to infer gene regulatory networks from gene-expressed data from singing animals. We found that each vocal nucleus has a distinct, but still partially overlapping, network of regulated genes. Many of the genes are involved in basic cellular processes, and a subset are differentially expressed during vocal learning.

Conducting these projects required that we further characterize the global organization of the avian brain and its homologies with mammals, decipher the limits of vocal plasticity and associated brain circuits for ultrasonic songs in mice, sequence the genomes of representatives of all vocal-learning avian species and their close relatives, and develop computational tools to identify convergent molecular changes in the genomes or brain regions that control complex traits.

These advancements will give us the ability to decipher the signal transduction and gene regulatory mechanisms of song, a quantifiable natural behavior with analogies to human speech. Since vocal pathways follow a connectivity design similar to other sensory and motor-learning neural systems, the study of vocal-learning systems yields insight into sensorimotor systems of the vertebrate brain.

This work was supported by grants from the National Institutes of Health, the National Science Foundation, the Klingenstein Foundation, the Packard Foundation, and the Human Frontiers in Science Program.

As of May 4, 2016

Scientist Profile

The Rockefeller University
Molecular Biology, Neuroscience