Andrew H. Bass, Cornell University
Project Title: Molecular-neural basis for motor patterning of vocal-acoustic signals.
Proposal Number: 1453167
Understanding how the brain controls behavior is a major goal in neuroscience. All behavioral actions, including those as different as walking, singing, even tiny eye movements that allow one to focus on a page of text, ultimately depend on the activation of muscles by motor neurons in the brain. The remarkable range of actions of which our bodies are capable of begs the question: how different are the motor neurons underlying different behaviors? One strategy for answering this is to compare neurons driving different behaviors. Teleost fishes are champions in the ability to generate vocalizations that exhibit rapid, precisely timed sound pulses. The studies proposed here use fish as model systems to compare vocal motor neuron populations to those that pattern non-vocal motor behaviors: locomotion dependent on movement of the fins, and electric signaling generated by modified muscle cells that are used by fish for communication and active sensing of the aquatic environment. The project will determine the extent to which molecular, genetic and physiological properties are shared in motor neurons driving these behaviors that differ in their temporal patterning, for example, fast (vocal and electric) vs. slow (fin movement). The Principal Investigator will continue to recruit a talented population of students of both sexes from diverse backgrounds, including underrepresented minorities, and train them in behavioral, neural, and molecular levels of analysis.
More specifically, three aims will use molecular, genetic and neurophysiological methods in several model systems among fishes to address the following questions: 1) Can similarities in the neurophysiological patterning of vocal motor behavior between distantly related species be explained by a similar set of gene products that underlies a shared set of vocal motor neuron characters (Aim 1)? 2) Do vocal motor neurons employ a “molecular toolkit” distinct from that of non-vocal motor neurons exhibiting lower degrees of synchrony and temporal precision, in this case the pectoral motor system for locomotion (Aim 2)? 3) Do vocal motor neurons employ a shared “molecular toolkit” with that of non-vocal motor neurons exhibiting comparable degrees of synchronicity, temporal precision and rapid firing, in this case the electromotor system that is used for active sensing of objects in the aquatic environment (Aim 3)? By complementing large-scale gene expression studies with neuro-pharmacological validation, these aims will identify how patterns of gene expression determine neurobiological and behavioral phenotypes, in this case those determining divergent motor functions.
​
​
​
Andrew H. Bass, Cornell University
Project Title: Midbrain Motor Coding of Vocal Behavior
Proposal Number: 1656664
Understanding how the brain controls movement is a major goal of neuroscience. All classes of motor actions depend on the brain for selecting and sequencing behavior-specific muscle activity patterns. This includes vocalization, a behavior that is widely shared among fishes, amphibians, birds and mammals. How do brain regions that control movement select between available subsets, such as alarm vs. courtship-calls or running vs. walking? How do brain regions then sequence these patterns into actions appropriate to meeting an environmental challenge? Vocal behaviors are excellent models for answering these questions, as they are often highly stereotyped within a species, differing in a finite set of easily quantified parameters such as frequency, amplitude and duration. There remains an astonishing lack of knowledge of how different brain regions participate in vocal performance, especially for the midbrain that is a key link between forebrain regions such as the basal ganglia and hypothalamus, and central pattern generators found in the hindbrain and spinal cord that instruct the activity of muscles. Vocal fish are highly tractable models for studying how the midbrain codes different vocal motor behaviors due to a small vocal repertoire directly controlled by a well-characterized and experimentally accessible vocal central pattern generator. The project will investigate the role of the midbrain in the selection, sequencing and/or patterning of different vocal motor behaviors. The Principal Investigator will continue to recruit a talented population of students from diverse backgrounds, including under-represented minorities, and train them in problem-solving at behavioral, neural and molecular levels of analysis.
More specifically, behavioral, neurophysiological and molecular methods will be used to provide the first comprehensive analysis of how the midbrain of a non-mammal contributes to vocal motor coding and action selection and more broadly the neural basis of vertebrate motor behaviors. Two major aims will test the hypothesis that the midbrain plays a role in selecting, sequencing and/or patterning vocal motor behavior in a species of teleost fish, the midshipman, for whom vocalization plays an essential role in their survival and reproductive success. Aim 1 will map specific populations of midbrain neurons that are activated during different vocalizations by detecting sites of immediate early gene (IEG) expression, a proxy for increased neural activity, in brains collected from fish that were actively vocalizing. This aim, will also characterize IEG-identified vocal populations by identifying co-expression with excitatory and inhibitory neurotransmitters and neuromodulators that we know can modulate midbrain-evoked vocal activity. fictive calling from our prior and new pilot studies. Guided by the results of Aim 1, Aim 2 will investigate the role of midbrain neuron populations in the selection, sequencing and/or patterning of vocal behavior by combining neurophysiology, including recording the activity of single neurons, with pharmacological manipulations to characterize the role of the neurochemicals studied in the first aim on their ability to induce and modulate vocal motor activity. By complementing behavioral and neuro-molecular studies (Aim 1) with neuro-pharmacological validation (Aim 2), these aims will identify how divergent types of vocal behaviors are selected, sequenced and patterned by the brain.