Gary J. Rose - US grants

The primary goal of this research program is the understanding of how the vertebrate central nervous system processes sensory information and organizes behavioral responses. This research, based on previous ethological and neurobiological studies, will be conducted with two species of weakly electric fish. By utilizing intracelluylar recording, physiologically characterized neurons can be filled with lucifer yellow or HRP and structure-function relationships in laminated structures can be addressed. Using stimulus regimes effective in driving the Jamming Avoidance Response (JAR), midbrain neurons of Eigenmannia have been identified which are sensitive to spatially static modulations of signal amplitude and differential phase. While these studies have provided some insight into the functional differentiation of particular laminae and the relationship between cell morphology and function, a more complete understanding requires that additional stimulus parameters be considered. It is particularly important to characterize single units in the torus semicircularis and optic tectum with regard to their sensitivity to spatio-temporally varying modulations in signal amplitude and differential phase (i.e., sensitivity to the motion of resistive and capacitive elements). Sternopygus, a species closely related to Eigenmannia, provides a natural test of whether "sign-sensitive" neurons of the torus and "sign-selective" tectal cells are, in addition to their role in the JAR, basic elements in the processing of object motion information. While Sternopygus has a laminated electrosensory midbrain which appears, at a gross morphological level, indistinguishable from that of Eigenmannia, this species does not have a JAR. The finding of sign-sensitive cells and sign-selective units in the midbrain of Sternopygus would lend support to this notion. The functional significance of lamination as a central processing scheme is a problem of general relevance to vertebrate sensory systems. The results of this research program therefore should provide needed insight into central processing mechanisms in sensory systems of higher vertebrates.

There are several fish with small electric organs, called weakly electric fish, that use their own electrical signal for "electrolocation" much as a bat or dolphin uses emitted sound (sonar) for echolocation of objects. Many of these fish produce an ongoing electrical waveform of nearly constant frequency to produce an electrical field around the fish, and special electroreceptors in the skin all over the body detect distortions in this field when objects are nearby. A reflex called the "jamming avoidance response" also is used by some fish to alter their own frequency if there is another signal in the water at close to the same frequency, that otherwise would mask out the fish's own signal. The neural circuits for parts of this detection system are now fairly well known, and a particular area of interest is part of the midbrain called the torus semicircularis. This project will investigate how neurons in the different layers of the torus respond to spatial and temporal changes in signal amplitude and phase, and how those responses are affected in the presence of jamming signals. Extracellular and intracellular recording will be used, along with labelling physiologically characterized neurons with dye to identify their location and connections. Responses will be compared between species with and without the jamming avoidance response, to identify which neural elements of the sensory-to- motor pathway are involved in that stereotyped behavior. This study exploits the well-described circuitry for electrosensory detection and its link to some highly quantifiable behaviors. Results from this novel approach will be valuable to sensory neuroscience in general, because they address problems of signal detection in noise, of motion detection and its discrimination from self-movement, and the functional role of layers in brain structure.

The neural causes of dysfunctional motor behavior are often addressed in terms of impaired integrative circuitry. Parkinsonian patients, for example, suffer a loss of fine motor control when the basal ganglia are no longer regulated by nigral dopaminergic afferents. Yet, an almost involuntary, ballistic behavior can be elicited by a sudden stimulus: patients may leap from their chair when startled. Thus, an abrupt change in the sensory image of their surrounding environment is immediately integrated with motor circuitry. In particular, sensory information may be integrated with the more primitive reticulospinal motor network to generate an adaptive response. The short latencies of these motor behaviors preclude sensory modification of the response immediately after it is initiated. Thus, a continuously updated sensory image of the environment must be available for use in selecting or biasing the ensuing motor program. Our goal is to elucidate some of the common principles involved in the integration of such neural networks. We hope to determine how a highly specialized sensory system is integrated with a primitive motor system to allow an animal to continuously monitor its environment and produce accurate ballistic behaviors. Electrosensory modulation of the escape system in fish is a relevant and experimentally tractable type of neural integration. The teleostean electrosensory system is known to be used for electrolocation, social communication, control of the Jamming Avoidance Response, and electromotor control during lateral and longitudinal tracking. The Mauthner (M-) cells, a bilateral pair of medullary neurons used to initiate the startle response, are present even in primitive fishes. While past studies have found auditory, visual, and lateral line afferents to the M-cells, we have recently shown that the electrosense can modulate the startle response of electrogenic gymnotiform fish. Physiological recordings from the inhibitory axon cap of the M-cell have demonstrated synaptic potentials in response to amplitude modulations of the fish's electric signal. The specific aims of this project are to 1) examine the influences of electrosensory cues on startle by looking at the effect of cue duration, the roles of ampullary (low frequency) or tuberous (high frequency) stimuli, and jamming stimuli on modulating the response. 2) Acute experiments will determine the lateralization of M- cell inhibition by simultaneously recording from the axon caps of both M-cells while reproducing the most behaviorally relevant stimuli. 3) Chronic recordings in freely behaving fish will verify the integration of the electrosensory surround in modulating the startle response.

DESCRIPTION (provided by applicant): The long-term objectives of this research program are to understand how temporal patterns in communication sounds are represented and processed in the central auditory system. Much of the information in communication signals, including human language, resides in their temporal structure. An understanding of how the temporal structure of sounds is represented and processed in the nervous system, therefore, is vital to understanding the neural bases of communication and communicative disorders. The research will be conducted on the auditory system of anurans because the temporal structure of their vocalizations has been shown to be important in their reproductive biology and behavioral studies can be conducted to delineate their temporal processing abilities. Presently, little is known concerning the neural mechanisms of temporal processing in the auditory system. At a basic level, the temporal structure of sound consists of how its amplitude and frequency changes, i.e., is modulated, over time. The specific goals of this research project are to gain insight into how amplitude modulations are represented in the brain and the transformations in these representations. In a number of vertebrate species, including mammals, there is a transformation from a periodicity coding of the rate of amplitude modulation to an AM filter representation; most neurons in the midbrain respond best over a particular range of AM rate, i.e., are band-pass. The mechanisms underlying this transformation are poorly understood. Previous work showed that integration and recovery processes are important in generating AM filters. The specific experiments outlined in this research proposal are designed to test hypotheses concerning the mechanisms that underlie these integration and recovery processes. Other experiments will investigate whether relations exist between a neuron's selectivity to AM stimuli and its location and/or morphology.

DESCRIPTION: (Adapted from the Investigator's Abstract) The long-term objectives of this research program are to understand how temporal patterns in communication sounds are represented and processed in the central auditory system. Much of the information in communication signals, including human language, resides in their temporal structure. An understanding of how the temporal structure of sounds is represented and processed in the nervous system, therefore, is vital to understanding the neural bases of communication and communicative disorders. The research will be conducted on the auditory system of anurans because the temporal structure of their vocalizations has been shown to be important in their reproductive biology and behavioral studies can be conducted to delineate their temporal processing abilities. Presently, little is known concernng the neural mechanisms of temporal processing in the auditory system. At a basic level, the temporal structure of sound consists of how its amplitude and frequency changes, i.e., is modulated, over time. The specific goals of this research are to gain insight into how amplitude modulations are represeted in the brain and the transformations in these representations. In a number of vertebrate species, including mammals, there is a transformation from a periodicity coding of the rate of amplitude modulation to an AM filter representation; most neurons in the midbrain respond best over a particular range of AM rate, i.e., are band-pass. The mechanisms underlying this transformation are poorly understood. The specific experiments outlined in this research proposal are designed to test hypotheses concerning the generation of band-pass AM selectivity. The roles of recovery processes and temporal integration will be investigated. Other experiments should reveal whether an 'AM map' exists in the midbrain.

The long-term objectives of this research program are to understand how temporal patterns in communication sounds are represented and processed in the central auditory system. Much of the information in communication signals, including human speech, resides in their temporal structure, and deficits in processing temporal information underlie disorders in speech recognition. An understanding of how the temporal structure of sounds is represented and processed in the nervous system is vital, therefore, to understanding the neural bases of communication and communicative disorders. The research will be conducted on the auditory system of anurans because the temporal structure of their vocalizations has been shown to be important in their reproductive biology, and they are well suited for neurophysiological investigations of the mechanisms that underlie temporal processing. At a basic level, the temporal structure of sound consists of how its amplitude and frequency changes, i.e., is modulated, over time. The specific goals of this research project are to gain insight into how amplitude modulations, including pulse duration and rise time, are represented in the brain and the mechanisms that underlie transformations in these representations. In a number of vertebrate species, including mammals, there is a transformation from a periodicity coding of the rate of amplitude modulation to an AM filter representation;most neurons in the midbrain respond best over a particular range of AM rate, i.e., are band-pass. The mechanisms underlying this transformation are poorly understood.

DESCRIPTION (provided by applicant): The long-term objectives of this research program are to understand how temporal patterns in communication sounds are represented and processed in the central auditory system. Much of the information in communication signals, including human speech, resides in their temporal structure, and deficits in processing temporal information underlie disorders in speech recognition. An understanding of how the temporal structure of sounds is represented and processed in the nervous system is vital, therefore, to understanding the neural bases of communication and communicative disorders. The research will be conducted on the auditory system of anurans because the temporal structure of their vocalizations has been shown to be important in their reproductive biology, and they are well suited for neurophysiological investigations of the mechanisms that underlie temporal processing. Presently, little is known concerning the neural mechanisms of temporal processing in the auditory system. At a basic level, the temporal structure of sound consists of how its amplitude and frequency changes, i.e., is modulated, over time. The specific goals of this research project are to gain insight into how amplitude modulations, including pulse duration and rise time, are represented in the brain and the mechanisms that underlie transformations in these representations. In a number of vertebrate species, including mammals, there is a transformation from a periodicity coding of the rate of amplitude modulation to an AM filter representation; most neurons in the midbrain respond best over a particular range of AM rate, i.e., are band-pass. The mechanisms underlying this transformation are poorly understood. Previous work suggests that interplay between excitation, inhibition and plasticity underlies the selectivity of midbrain neurons for AM rate, sound duration and possibly rise time. The specific experiments outlined in this research proposal are designed to further elucidate how these synaptic properties are integrated by midbrain neurons to generate selectivity for these temporal features of sounds. PUBLIC HEALTH RELEVANCE: Presently, little is known concerning the neural mechanisms of temporal processing in the auditory system. Previous work suggests that interplay between excitation, inhibition and plasticity underlies the selectivity of midbrain neurons for AM rate, sound duration and possibly rise time. The specific experiments outlined in this research proposal are designed to further elucidate how these synaptic properties are integrated by midbrain neurons to generate selectivity for these temporal features of sounds.

The temporal structure of signals plays important roles in communication. The proposed projects aim to provide new insight into how midbrain neurons respond selectively to particular temporal features of communication sounds, specifically pulse rate, duration and shape. Experiments will investigate the role of NMDA-type receptors in amplifying responses and augmenting temporal selectivity. Other experiments will be the first to explore the role of projections from the nucleus of the lateral lemniscus to the inferior colliculus in generating temporal selectivity. Focal pharmacological manipulations will be combined with whole-cell intracellular recordings. This novel and powerful methodological approach has only recently been applied to the in vivo study of central auditory systems (Rose et al., 2013), and holds great promise for enabling auditory system researchers, as well as the neuroscience community at large, to gain unprecedented insight into the mechanisms that underlie computations in the brain. This approach will also be used to investigate the roles of dynamic properties of inhibition, and thereby evaluate a new model of interval selectivity. The last set of experiments will investigate the mechanisms that underlie selectivity for pulse shape. These new experiments are expected to further our understanding of the network and cellular properties that underlie the temporal selectivity of midbrain neurons.

The temporal structure of signals plays important roles in communication. The proposed projects aim to provide new insight into how midbrain neurons respond selectively to particular temporal features of communication sounds, specifically pulse rate and duration. Experiments will investigate the role of NMDA-type receptors in amplifying responses and augmenting temporal selectivity. Other experiments will be the first to explore the role of projections from the nucleus of the lateral lemniscus to the inferior colliculus in generating temporal selectivity. Focal pharmacological manipulations will be combined with whole-cell intracellular recordings. We also propose to use new computational methodology to delineate the time course of excitatory and inhibitory conductances. This novel and powerful methodological approach has only recently been applied to the in vivo study of central auditory systems (Rose et al., 2013), and holds great promise for enabling auditory system researchers, as well as the neuroscience community at large, to gain unprecedented insight into the mechanisms that underlie computations in the brain. This approach will also be used to investigate the roles of dynamic properties of inhibition, and thereby evaluate a new model of interval selectivity. The last set of experiments will investigate whether IC neurons of the various temporal selectivity classes respond selectively to particular natural calls of leopard frogs. These new experiments are expected to further our understanding of the network and cellular properties that underlie the temporal selectivity of midbrain neurons.

Mechanisms of behavioral sex plasticity in sex-changing wrasses The biological processes that underlie behavioral sex phenotype are incompletely understood. Organisms that naturally undergo sex transformations in response to changes in their social environment provide excellent systems in which to investigate mechanisms of behavioral sex specification. Bluehead wrasses in particular are well suited for addressing this problem. Adult females can switch sex in response to changes in social structure. Further, behavioral sex transformation can occur rapidly, thereby providing an opportunity to investigate the neurobiological basis of this plasticity. We propose to further develop this system as a model for investigating mechanisms of plasticity of behavioral sex phenotype. The proposed work builds on our ?priming/gating? hypothesis of behavioral sex transformation; this hypothesis accounts for the relation between social rank and competency for transformation. Our first objective is to compare the expression of the immediate-early genes, c-Fos and p-S6, in courting and non- courting fish. We expect that results will further elucidate the neural circuits that control the expression of male-typical courtship behavior. To test for causal roles of these circuits in courtship behavior, we plan to iontophorese glutamate to discretely activate particular brain regions and monitor courtship-related changes in skin coloration. Our goal is to identify properties of neural circuits that underlie competency to undergo behavioral sex transformation.