Jagmeet S. Kanwal, Ph.D. - US grants

DESCRIPTION: (Adapted from the Investigator's Abstract) Mustached bats, Pteronotus parnellii, emit a diverse array of structurally complex communications sounds (calls) as well as stereotypic echolocation pulses. Surprisingly, many auditory cortex neurons that were previously considered to be "highly specialized" for processing echolocation signals, especially those in the left hemisphere, respond equally well or better to calls. First, with continued support, the work proposed here will electrophysiologically characterize the nature and extent of the hemispheric lateralization for processing calls. This will be accomplished largely by simultaneously recording from both hemispheres while presenting the appropriate call and echolocation (pulse-echo pair) stimuli and mapping stimulus preference, at both the population and single cell levels. Second, this research will explore auditory processing beyond the level of the auditory cortex by recording auditory responses in the frontal cortex. Despite over twenty years of auditory cortical research, very little is known about auditory responses within the frontal cortex of any species. Frontal auditory (FA) responses can be dramatically different from those in the auditory cortex. The proposed work will fill this gap by characterizing and categorizing FA neurons in a quantitative manner. A variety of species-specific calls and basic acoustic patterns (e.g., frequency modulated sweeps, constant frequency tone and noise bursts) will be presented and neurophysiological data will be acquired under computer-control. The final thrust of this proposal is to examine the role(s) of intracortical interactions during short-term auditory processing. Inter-hemispheric interactions may create hemispheric lateralization and fronto-temporal interactions may modify responses of echolocation and call processing neurons. To examine this short-term regulation, auditory stimulation will be paired with electrical microstimulation and transient focal inactivation of neurons in the auditory cortex on one side, while recording responses of single cells in the auditory cortex on the opposite side. Specific parameters to examine include (1) peak response rate, (2) response latency, (3) response duration, (4) temporal response patterns, and (5) call preference of neurons. This research will bring us closer to understanding call processing at the cortical level in mammals, and the basic auditory mechanisms for perceiving speech sounds in humans. It can have an especially important bearing on understanding different types of cortical deafness such as progressive pure word deafness.

Animal models of auditory communication are especially relevant for studies on auditory communication in infants who primarily engage in nonverbal communication. Nonverbal communication is the only means of communication in animals. An understanding of the cortical mechanisms for processing and integration of communicative sounds can provide insights into the cellular basis of human speech and how it evolved from the available neural circuitry.
The proposed research will explore the role of the frontal cortex for audiovocal social communication in bats.
We will develop and deploy a behavioral assay to examine how the absence of a frontal auditory field and the anterior cingulate affects the perception and production of social calls, e.g.,
broadband noisy syllables that are emitted during aggression. The behavioral assay will allow us to assess in a quantitative fashion the response to both normal and modified communication sounds in normal and brain-lesioned animals. Cortical lesions will be localized using magnetic resonance imaging technology and, if necessary, their functional inactivation will be confirmed using electrophysiological recording techniques. The acoustic structure ofvocalizations in animals with lesions in the frontal cortex and microstimulation of these areas in normal animals will examine the role of the frontal cortex in regulating the spectral and syntactic structure within communicative vocalizations.
This research will provide new insights on the relationship, if any, of the frontal cortical areas in bats with the so called "language areas" associated with speech sound perception and production in humans.

[unreadable] DESCRIPTION (provided by applicant): Audiovocal organization in the amygdala forms the neural substrate for adaptive behaviors that include motivational and affective regulation of vocal activity. The first objective of this project is to describe the representation of social calls in the basolateral amygdala. A second objective is to localize the interface between call representation and vocal expression in the amygdala. At present, we know very little of this organization in the mammalian amygdala. The proposed studies will be conducted in mustached bats since this species is highly social and vocal. The auditory system of this species is well developed and well studied. Local field potential recordings combined with single unit recordings from the amygdala will reveal the spatial organization for representing different call types including pitch-shifted call variants. Using statistical procedures, the auditory representation will be tested for an acoustic structure versus motivational value based match. A motivational-value based representation will allow for an aggressive versus affiliative grouping of neurons, whereas an acoustic structure-based organization will conform to the segregation of auditory and/or vocal activity according to acoustic features, e.g., fundamental frequency, pitch, loudness and/or direction of frequency modulations. Call selectivity will also be quantified along the dorso-ventral (lateral to basal nuclei) trajectory at several planes along the anterior-posterior axis within the basolateral amygdala. An acoustic structure to motivational value transformation is expected in auditory-to-vocal mappings within the basolateral amygdala. Therefore, at the end of each recording session, electrical microstimulation will be performed to reveal the patterns of vocal activity represented within the amygdala. Taken together, these data will reveal for the first time whether audiovocal learning and memory, e.g., via fear-conditioning, is embedded within a contingency/motivational-value (reward or pain) based and/or an acoustic- structure based frame-of-reference within the amygdala. PUBLIC HEALTH RELEVANCE The proposed research will elucidate the functional organization of the neural substrate within the amygdala for nonverbal audiovocal communication, including the vocal expression of affect and the prosodic content in speech. This research will identify the neural signatures for the representation of affiliative versus aggressive calls. The new findings have the potential to help us understand and resolve the neural defects in communication-related social disorders, e.g., stuttering and autism-spectrum disorders. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): By studying the brain in live and behaving subjects, we obtain fundamental insight into the neural basis of natural behaviors. Such basic biology research is essential as the fundamental underpinning for understanding brain function when compromised by disease or injury. In this proposal we will investigate the brain mechanisms for modulating the flow of sensory information to the cerebral cortex, where perception occurs. With only minor exceptions, all sensory signals are relayed to cortex through a brain structure called the thalamus. Other parts of the brain modulate thalamic throughput by specific kinds of projections or neurotransmitters. Depending on the "tone" of these various inputs, the thalamus switches between two different modes of relay. One mode relays sensory information very faithfully;whereas, the other distorts or disconnects the relayed information. The faithful "tonic mode" predominates during wakefulness and the other "burst mode" predominates during deep sleep. The nature of the transition between these two modes in the living animal is currently not well understood, and will be investigated here. A major source of influence for this state-related tone comes from a brainstem structure called the parabrachial region (PER) that uses the special neurotransmitter acetylcholine. In order to understand this "gate keeper" action better, we intend to manipulate the activity in the PBR experimentally while observing the effect in the visual relay nucleus of the thalamus, the lateral geniculate nucleus (LGN). Essentially, we will use the visual system to understand how the PBR "arouses" the thalamus. The health relatedness of this research is that study of how the normal, healthy brain works is how we come to understand the human condition in health and in illness.