1985 — 1989 |
Bass, Andrew H |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Hormonal Influences On the Neurobiol of Excitable Cells @ Cornell University Ithaca
I am studying the influences of gonadal steroid hormones on the anatomical and physiological properties of action potential- generating (i.e. electrically excitable) cells. I am using the electromotor system of mormyrids, a group of weakly electric fish from Africa, as a model system. Mormyrids have an electric organ located in the tail that consists of modified muscle cells called electrocytes that together generate an Electric Organ Discharge (EOD). The characteristic properties of the EOD are determined by the anatomy and physiology of the electrocytes. The activity generated by a single electrocyte determines the appearance of the entire EOD. I have found that gonadal steroid hormones (e.g. testosterone) can induce changes in the EOD that mimic natural sex differences. Steroid-induced changes in the EOD are correlated with changes in the morphology of the electrocyte's excitable membranes and the duration of their action potential waveforms. I want to continue studying the cellular mechanisms underlying hormone- induced changes in the anatomy and physiology of the electric organ. I also want to extend my anatomical studies of steroid- binding cells in the brain of electric fish. The effects of steroid hormones on electrocytes may be fundamental to their action on other classes of electrically excitable cells, namely neurons and muscle fibers. The EOD itself is somewhat unique in that it is both a behavior, important in an electrical guidance system and in social communication, and a discrete neurophysiological event. In this way, we can weave an interface between steroid hormone action at functional (i.e. behavior) and mechanistic or cellular levels.
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0.958 |
1987 — 1995 |
Bass, Andrew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Structure-Function Studies of a Sonic (Acoustic) Motor System
Vocal communication in vertebrate animals is one behavior that displays sexually dimorphic characteristics (i.e., males and females are different). Dr. Bass has chosen to study teleost fishes as a model system of this type of behavior. In the species to be studied males generate vocalizations in order to attract females to the nest, but no such behavior is seen in the females. In previous studies it has been shown that the behavioral sex differences in vocalizations are correlated with anatomical and physiological traits of the muscles and neurons that comprise the sonic motor pathway. The proposed research will study the underlying basis of these differences. The electrophysiological properties of the nerve cells involved in these responses will be analysed. The morphological features and the chemical nature of specific nerve cells in this system will be identified. Changes induced by testosterone, a reproductively active steroid hormone, will be measured both physiologically and anatomically. These studies will contribute to fundamental knowledge about the role of steroid hormones in the regulation of nerve cell function and sexually differentiated behaviors in vertebrates.
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1992 — 1993 |
Bass, Andrew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Sger: Ontogeny of Gnrh Expression Vertebrate Neurons
Gonadotropin-releasing hormone (GnRH) is a decapeptide that was isolated from brain in 1971. With the development of sophisticated antibody technology, the GnRH neuronal network was demonstrated to be a complex, heterogenous system, comprising three or more discrete neuronal groups and spanning vastly different regions of the brain, including the ganglion of the terminal nerve within the olfactory bulb and nerve, the basal forebrain including the preoptic area, and the caudal diencephalon or midbrain region. Moreover, GnRH neurons project to targets within and outside the brain and serves as both a hormone and a neurotransmitter. It is implicated in controlling the expression and maintenance of neuroendocrinological traits underlying behavioral reproductive mechanisms. This Small Grant for Exploratory Research award to Dr. Bass will facilitate the development of sensitive and specific molecular tools which will be instrumental in providing new insights into the cellular and molecular bases for hormonal control of sexual differentiation of brain and behavior. He will complete the sequence analysis and sequence comparisons of cDNAs for GnRH in a specific species that serves as a model to examine intrasexual dimorphisms in brain and behavior. Dr. Bass will use the antisense ribonucleic acid transcripts generated from the cloned cDNAs and in situ hybridization histochemistry to identify the expression patterns and quantitate levels of novel GnRH transcripts in the brain of juvenile and adult animals with distinct reproductive phenotypes. The development of these new sensitive molecular tools will open up new avenues into this emerging research area. The research will lead to a better understanding of the role that GnRH plays in basic mechanisms underlying reproducive maturation, physiology and species-typical behaviors.
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1993 — 2011 |
Bass, Andrew H |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Encoding of Vocal Signals in the Auditory System
The discovery of estrogen-dependent plasticity in the peripheral auditory system of teleost fish provides an ideal model for establishing the cellular, molecular and neurophysiological mechanisms leading to steroid modulation of audition. Female midshipman fish use the multi-harmonic vocalizations ("hums") of males for mate localization and exhibit dramatic reproductive state- dependent shifts in the encoding of the male's hum by eighth nerve afferents that innervate the saccule, the main peripheral auditory organ in teleosts. Thus, the primary saccular afferents of reproductive females, compared to those of non-reproductive females, show an increase in best frequency and improvement in the precision of temporal encoding (via phase-locking) to the upper harmonics of male hums. Either 17|3-estradiol or testosterone treatment of non-reproductive females for 3-5 weeks induces the enhanced auditory phenotype of reproductive females, consistent with transcriptionally-dependent events. The observed changes are likely entirely due to estrogen that circulates at two fold higher levels in reproductive females. In addition, auditory ganglion cells adjacent to the saccule's hair cell layer express the enzyme aromatase that converts testosterone.to estrogen, and can therefore aromatize circulating testosterone to augment the locally available source of estrogen. Two specific aims will investigate estrogen-dependent shifts in molecular (potassium channels and estrogen receptors) and neurophysiological (hair cell and primary afferent encoding) mechanisms that can lead to improvements in temporal processing via phase-locking in the auditory system. The proposed studies will also delineate mechanisms of sensorineural plasticity that are relevant to shifts in age-related hormonal states, including changes in audition that occur during the reproductive cycle and in clinical syndromes"associatedwith abnormal patterns of hormone secretion (e.g., Turner's Syndrome)..Lastly, the proposed experiments will lead to a more fundamental understanding of how deficits in the temporal encoding of acoustic signals, dependent on phase-locking mechanisms, contribute to impairments in hearing observed among humans including those .with auditory; neuropathy/dys-synchrony.. '-.'[unreadable]......
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0.958 |
1995 — 2000 |
Bass, Andrew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Neural and Endocrine Regulation of Vocal Communication
9421319 Andrew H. Bass Verbal and non-verbal communication skills are widely used throughout the animal kingdom for mate selection and reproduction, food collection and formation of social structures. However, the brain mechanisms involved in communication are frequently complex and difficult to study. Dr. Bass, a highly regarded behavioral neuroendocrinologist, has identified and characterized a unique neural system of vocal communication in a simple vertebrate species during his previous investigations. This system is unique in that a single muscle is responsible for the generation of sound. In the present study, Dr. Bass will use a highly creative and integrative approach to study the brain mechanisms involved in generating rhythmical vocal behaviors and the role of androgens in gender-specific differentiation of that circuitry and behavior. Previous studies identified a brain command center for vocal behavior and electrical recordings will be used to determine the anatomical connections of the system. Additional studies will investigate the ability of androgenic hormones to act within this command center to facilitate the development of vocal behaviors in these animals. These studies have the potential to define the actions of hormones on neural pathways leading to behavior changes, which may be applicable to other species including man.
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2000 — 2006 |
Bass, Andrew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Integration of Neuroendocrine and Vocal Mechanisms
These studies will identify how the neuropeptides (arginine vasotocin, AVT and isotocin, IT) and steroid hormones influence neural circuits that generate vertebrate social behaviors, in this case vocalization. The project will investigate: (1) the development and steroid-dependent plasticity of neuropeptide modulation of vocal-related neurons, and (2) the role of aromatase, an enzyme that converts testosterone to estradiol, in regulating steroid effects on vocal neurons either directly and/or indirectly via their influence on neuropeptides. The goals will be achieved using neurophysiological, neuroanatomical, biochemical and behavioral methods.
Vocalization behaviors are central to mediating social interactions in animal groups as diverse as fish and humans. This lab studies the neuroendocrine control of vocalization in fish with two male types or morphs. Among midshipman fish, "singing" males court females with a "song", while "sneaking" males neither sing nor court females but instead steal fertilizations from singing males that have attracted females to their nest. Although all adults produce agonistic calls, sound production differs here too with social context for the male morphs and females. The neurophysiological properties of a pattern generator that establishes sex- and morph-typical vocalizations is directly influenced by the action of AVT and IT (the fish equivalents of arginine vasopressin and oxytocin in mammals) in the preoptic area-anterior hypothalamus, a brain region implicated in the control of social/vocal behaviors across all vertebrates. The pattern of AVT and IT modulation is dependent on social/vocal behavior, not gonadal sex. These patterns are also paralleled by differences in aromatase levels in vocal brain regions. Together, these findings provide a unique opportunity to investigate the separate and/or interactive effects of peptides and steroid hormones on brain circuitry that determines social behaviors.
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2004 — 2006 |
Bass, Andrew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Dissertation Research: Field Study: Do Steroid Hormones Cause Rapid Changes in the Behavior of a Vocal Teleost?
DISSERTATION RESEARCH: Field study: Do steroid hormones cause rapid changes in the behavior of a vocal teleost?
Luke Remage-Healey and Andrew H. Bass
Abstract
Like many vertebrates, human beings experience rapid fluctuations in plasma steroid hormones in response to environmental stimuli, such as winning a chess match or watching a favorite sports team lose a critical game. Despite this, the psychological and/or behavioral impact of rapid hormonal changes is poorly understood. Animal models provide a way to experimentally test how neural and hormonal mechanisms regulate rapid changes in behavior. This proposal outlines experiments that will test how rapidly-changing hormone levels may directly lead to rapid changes in vocal communication behavior in a teleost fish. In this study, experimental manipulation of the internal hormonal and external social environments will aid our understanding of the neural, behavioral and endocrine interactions that are common to all vertebrates, including humans. This project will also continue to train field assistants according to a strong commitment to advancing students from a variety of backgrounds and origins.
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2005 — 2011 |
Bass, Andrew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Behavioral Neuroendocrinology of Vocal Communication
Steroid hormones exert powerful effects on a wide range of mechanisms ranging from development and reproduction to cognition and the establishment of social hierarchies. The new studies proposed here will identify the cellular and molecular events that mediate rapid steroid actions on nerve cells (neurons) that directly generate behavior, in this case vocalizations that are essential for social communication. Long-term influences of steroids on the development and maintenance of vocal behaviors and neurons is well known, but their short-term actions is both unexpected and essentially unexplored. The vocal control system of teleost fish presents the most basic example of how the central nervous system of vertebrates produces social, context-dependent vocalizations. The PI has discovered that androgens, estrogen and cortisol (the major "stress" steroid in teleost fish) induce rapid changes in the output of vocal neurons that parallel the time course of steroid effects on natural calling behaviors. This now provides a model to study the physiological basis for rapid steroid effects on neurons that directly lead to changes in a social behavior. Neurophysiological, molecular and behavioral methods will be used to show how steroids shape neuronal function, where the receptors that mediate these effects are located, and how vocal behaviors are influenced by one or more steroids. The principles identified apply to other vertebrates because vocal, neural and endocrine mechanisms are evolutionarily conserved between teleosts and other groups, including birds and mammals. This research has, and will continue to, train undergraduate, graduate, and postdoctoral students of both sexes from diverse cultural backgrounds and geographic regions and make the results of the research easily accessible to the general public through publications, press interviews and presentations at professional societies, universities, marine biology laboratories and local community science centers.
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2011 — 2016 |
Bass, Andrew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Neural and Hormonal Mechanisms of Vocal Communication
Understanding how hormones influence the nervous system helps reveal how the brain controls social behaviors like vocalization (sound production). Investigations of the simpler nervous system of fishes demonstrate that hormones dramatically influence the activity levels of individual neurons and neuron-to-neuron interactions underlying vocal behavior. Among fishes, vocal mechanisms and behaviors have largely been studied in one group known as midshipman. These studies are guided by the recent discovery that naturally occurring daily variation in midshipman vocal behavior is determined by daily changes in the activity of vocal neurons. Other studies in midshipman show that steroid hormones such as androgens and neurochemicals such as gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the vertebrate nervous system, induce changes in vocal neuron activity that mimic daily changes in vocal behavior. Neurophysiological, molecular and behavioral methods will test the hypotheses that daily changes in vocal neuron activity and vocal behavior depend on the actions of androgens, GABA, and the hormone melatonin that profoundly influences daily behavioral rhythms in vertebrates. The principles identified will apply to other vertebrate groups because vocal, neural and hormonal mechanisms are evolutionarily conserved between fishes and other vertebrates, including birds and mammals. This research has and will continue to train undergraduate, graduate, and postdoctoral students from diverse cultural backgrounds and geographic regions and make the results of the research easily accessible to the general public through publications, press interviews and presentations at professional societies, universities, marine biology laboratories and local community science centers.
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2014 — 2016 |
Feng, Ni (co-PI) [⬀] Bass, Andrew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Dissertation Research: Melatonin Regulation of Vocal Behavior
Circadian rhythms that approximate the 24 hr day-night cycle, synchronize animal behavior and physiology to cyclical changes in environmental cues, such as light, temperature, and the availability of mates. How biological rhythms are generated by hormonal, genetic, and neural mechanisms is of great scientific interest. The nocturnal hormone melatonin plays a central role in entraining daily activity to the day-night cycle. In many mammals, activity and mating occur at night so there is potential for melatonin to regulate important reproductive behaviors such as vocalizations used in courtship. This project will investigate circadian and melatonin regulation of daily rhythms in the vocal behavior of a nocturnally active and highly vocal fish, the plainfin midshipman (Porichthys notatus) by answering three questions: (1) Is the daily vocal rhythm under internal, circadian control? (2) Does melatonin stimulate nocturnal vocal behavior? (3) Does melatonin regulate gene expression underlying neural excitability in vocal brain regions? These studies will contribute to a comparative framework for predicting melatonin regulation of vocal behavior in other species, including birds and mammals that exhibit divergent daily activity patterns. More broadly, melatonin has been implicated in sleep, jetlag, autism and epilepsy, making basic research on how it affects social communication and neural excitability important and widely applicable.
This project will test the overall hypothesis that the midshipman's nocturnal courtship vocalization is under circadian control and stimulated by melatonin. Proposed studies will (1) record vocalizations from naturally behaving fish under constant external light conditions to test for an internally generated circadian vocal rhythm, (2) implant fish with melatonin to test for melatonin regulation of vocal behavior, and (3) seek a deeper understanding of how melatonin influences daily rhythms in vocal behavior by examining its regulation of neural excitability-related gene expression in a well-characterized vocal network. If the midshipman daily vocal rhythm is under endogenous circadian control, it is predicted that rhythms recorded under a normal light regime will persist under constant darkness with a period of ~24 hr. Additionally, if midshipman vocal behavior is dependent on melatonin action, it is predicted that vocalizations will be reduced or abolished under constant light, shown to abolish melatonin production, while exogenous melatonin replacement under light will rescue the occurrence of vocalizations. Finally, the researchers predict that melatonin increases the expression of previously identified candidate genes known to affect neural excitability. These genes encode three types of ion channels and exhibit increased expression in a hindbrain vocal nucleus collected during the summer night, a time of maximal natural vocal behavior. Given conserved functions of the candidate genes explored in this proposal, such mechanisms could provide the molecular basis for translating the nocturnal melatonin signal to increase or decrease neural excitability in nocturnal versus diurnal animals, respectively. This project will train current and new undergraduates of both genders from diverse backgrounds, including underrepresented minorities. The results will be disseminated in open-access peer-reviewed journals, popular articles via online platforms, at national and international conferences, and at local science outreach events.
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2015 — 2020 |
Bass, Andrew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Molecular-Neural Basis For Motor Patterning of Vocal-Acoustic Signals
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 that animals 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. Modern bony 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 that depends on fin movement, 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 men and women students from diverse backgrounds, including underrepresented minorities, and train them in behavioral, neural, and molecular levels of analysis.
More specifically, molecular, genetic and neurophysiological methods in several model systems among fishes will be used 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.
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2017 — 2022 |
Bass, Andrew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Midbrain Motor Coding of Vocal Behavior
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 shared among fishes, amphibians, reptiles, birds and mammals. This remarkable behavior that includes human speech begs the general question: How do brain regions that control movement underlie our ability to select from a menu of available behavioral actions? Vocal behaviors are excellent models for answering this question because they are often highly stereotyped and differ in a small set of easily quantified properties such as frequency, amplitude and duration. There remains an astonishing lack of knowledge of how different brain regions participate in the performance of vocal behavior. This is especially the case for the midbrain that provides a key link between the cerebral hemispheres and central pattern generators found in the hindbrain and spinal cord that directly instruct the activity of muscles. Sound producing fish are champions in the ability to generate vocalizations that exhibit rapid, precisely timed sound pulses. They also provide highly tractable models for studying how the midbrain controls vocal behavior due to 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.
A practical way to address questions of how vocal motor systems function is to identify model systems, such as those in fish, where behavior is controlled by readily accessible brain centers that share evolutionary and developmental origins with centers in other vertebrates. This project has two aims that will use behavioral, neurophysiological and molecular methods to provide the first comprehensive analysis of how the midbrain of a highly species of vocal fish contributes to vocal motor coding and action selection. Aim 1 will map specific midbrain populations activated during different vocalizations by using immunohistochemistry to detect immediate early gene (IEG) expression, a proxy for increased neural activity, in brains collected from vocalizing fish. Aim 1 will also characterize the neurochemical signature of IEG-identified neurons by investigating co-expression with excitatory and inhibitory transmitters and select neuromodulators that are known to modulate midbrain-dependent mechanisms of vocalization. Aim 2 will then investigate the role of midbrain neuronal populations identified in Aim 1 in the selection, sequencing and/or patterning of vocal behavior by combining neurophysiology, including single neuron recording, with pharmacology to induce and modulate vocal motor activity. The results will inform us about vocal mechanisms and, more broadly, motor behaviors among all groups of vertebrates.
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