The ‘Missing Link’: Establishing the First Mammalian Model System for Investigating Vocal Learning and its Clinical Pathology

Lay Summary

Imaging the Learning of Language

Vocal learning, or the ability to hear a sound or word, imitate it, and develop language is often thought of as a required or necessary human ability, so much so that the lack of appropriate language acquisition is a hallmark of many neurological and developmental disorders in both adults and children. Despite a myriad of related research, the neural underpinnings of this essential human trait remain elusive.

Part of this dearth in knowledge can be attributed to the relative scarcity of animals with similar vocal learning facilities; out of over 5,000 known mammalian species, only three non-human mammals (cetaceans, elephants, and bats) possess vocal learning abilities.  In lieu of a mammalian model for vocal learning, much of our current understanding of vocal learning comes from avian models, which cannot be directly or easily translated to humans.

Using miniaturized microscopes in freely behaving bats, investigators will “image the learning of language” for the first time at a cellular level.  This novel imaging technique is capable of monitoring individual neurons over time, and allows for collection of data from up to several hundreds of neurons simultaneously over an extended learning process.  Over the bats’ normal 90-day period of language acquisition, these microscopes implanted in healthy bats will visualize changes to neural networks in two premotor cortical areas implicated in vocal production.

Researchers will use this same imaging technique in bats that are deaf from birth to see how deafness alters network development.  Using both healthy and deafened subjects will further our understanding of how deafness impairs neural networks integral to language.  The researchers hypothesize that in normal conditions, bats will develop organized language networks over the 90-day learning process, but these networks will remain unorganized in deafened bats.

Significance: The study is expected to produce the first mammalian model of how the brain develops the organizational capacity to acquire vocal language, and how these organizational processes are altered by developmental disorders and deafness. A more thorough understanding of these mechanisms will establish opportunities to develop improved clinical interventions for language disorders.

Abstract

Abstract: The ‘missing-­‐link’: Establishing the First Mammalian Model System for Investigating Vocal Learning and its Clinical Pathology

Vocal production learning, the process of using auditory input to modulate speech acquisition, is fundamental for the development of human language. Yet, evidence of such process are sparse across non-­‐human mammals and out of over 5000 mammalian species on our planet, the only non-­‐human mammals that have been shown to possess vocal learning abilities are: cetaceans, elephants and bats.

We have recently established techniques and behavioral procedures for neurophysiological investigation in freely behaving bats and here we aim to use these remarkable mammals to study the neural basis of language development. Specifically, the central aim of this proposal is to use cellular-­‐resolution calcium imaging methods in freely behaving bats to study mammalian neural networks underlying vocal learning for the first time.

Our hypothesis is that under healthy conditions an initially constrained network activity in the mammalian cortex will gradually develops during ontogeny to form stable neural networks with sparse representation of the adult vocabulary. In contrast, we hypothesize that following hearing loss resulting from deafness, the network activity will remain highly distributed. This research will provide the first insight into the underlying neural network processes that support vocal learning in the mammalian brain.

Our specific three aims for this proposal are the following:

(1) Establish a psychophysical paradigm where bats are trained on vocal production learning.

(2) Use miniaturized microscopes for calcium imaging to examine the neural underpinning of vocal learning under normal development in mammals.

(3) Use miniaturized microscopes for calcium imaging to examine the neural underpinning of vocal learning under diseased (deafness) conditions in mammals.

This research proposal will establish the bat as the first formal mammalian model system for vocal learning. Importantly, our proposed research is aimed at providing immediate clinically relevant insight into the influence of deafness on vocal learning centers in the mammalian brain. Combined, our research will provide important insight into the neural mechanisms underlying development and clinical deficits of language in mammals. Such deficits lie at the core of many neurodevelopment and mental disorders in both adults and children and are reflected in deficiencies in the acquisition and expression linguistic capabilities. The establishment of the first tractable mammalian model system for neural investigation of the development of language will accelerate the development of novel therapeutic approaches that would greatly benefit the human society.