The Computational Neuroethology lab investigates the neural mechanisms underlying natural social behaviors. We are interested in questions ranging from how neural circuits transform social cues into behavioral responses, what plasticity arises within those circuits as the meaning of social cues is acquired, and how that plasticity may be mediated by mechanisms driving social reward. We pursue these issues using two model systems where forms of learning occur in natural social contexts. The first is acoustic communication in mice, using a maternal model wherein mothers acquire recognition for the ultrasonic vocalizations of pups. The second system we study is social bonding in prairie voles.
Like a student in a foreign country immersed in an unfamiliar language or a young mother trying to decipher her baby's cries, we all encounter initially meaningless sounds that in fact carry meaning. As these sounds gain significance, we become better at detecting and discriminating between them. How does this happen? What brain changes underlie this? The processing of communication sounds is a fundamental task of virtually all auditory systems, yet how it is studied has often diverged along species lines. Research in nonmammalian animals - like insects, frogs and birds - routinely incorporates natural calls, which has led to the discovery of finely tuned mechanisms for vocalizations. In mammalian audition though, there has been far less systematic use of species-specific calls. Thus, we have still much to learn about the neural mechanisms underlying communication processing and learning in mammals.
We address this problem by using a mouse model of acoustic communication. Using the communication between mouse pups and adult females (mothers, cocaring females and naive virgins) as a model system to explore this, we have found evidence that neurons in the auditory cortex change the way they encode these sounds, improving their contribution to detection and discrimination.
We use electrophysiological, computational, molecular and behavioral methods to ask a variety of questions about how species-specific vocalizations are represented in the hierarchical auditory system. What are the electrophysiological and molecular correlates of learning the behavioral relevance of species-specific vocalizations, and how does this affect the function of those neural circuits? Are they genetically pre-wired or plastic, innate or experience-dependent? What influences do social experience and social neurochemicals like estrogen play? Answering these neuroethologically-inspired questions may give us insight into the neural basis and evolution of communication, and help elucidate mechanisms underlying auditory memories.
The change in neural activity we observe between virgins and mothers raises the question of how this plasticity arises. Are there also subcortical differences in processing? Do hormones or pup-experience drive the changes?
One of the steps we're pursuing to help identify putative cellular and molecular mechanisms for this is to study the expression of effector immediate early genes (IEG) in response to sound stimulation. Of particular interest is the cytoskeleton-associated gene Arc/Arg3.1, which has been strongly implicated in memory consolidation and function. This project involves fluorescent in situ hybridization (FISH) studies of Arc/Arg3.1 expression in animals stimulated by various sequences of natural and synthetic sounds. This is a collaboration with Gary Bassell's lab in Cell Biology.
We are also exploring whether an animal's physiological state affects the plasticity. Since motherhood involves not only experience with pups, but also profound hormonal changes, we are interested in understanding how these two factors may act together to produce sensory plasticity. This project involves neuroendocrine, behavioral and electrophysiological methods.
The acoustic environment during a sensitive period in development can profoundly influence neural responses to sound late into life. During this time, simple sound exposure is sufficient to drive plasticity; contrast this with plasticity induced during adulthood, which typically requires the pairing of a sound with a salient event. To elucidate conditions supporting sensitive period plasticity, we are investigating whether the neuromodulator norepinephrine (NE) is required for developmental plasticity in auditory cortex. This work builds on pioneering studies from the visual system that hinted at a critical role for NE, though this finding was hotly debated. By mapping frequency tuning across the spatial extent of the auditory cortices of NE-deficient and NE-competent mice, we hope to resolve whether NE is necessary for experience-dependent plasticity during auditory cortical development. This work could go on to inform studies of early life development across sensory systems, and of the neural events that underlie auditory learning. This work is supported by a predoctoral NRSA to Katy Shepard.
While numerous paradigms exist to study the neural basis for generic associative memories, few look specifically at whether systems for social memories differ from those for nonsocial memories. This is plausible given the growing evidence supporting the Social Brain Hypothesis, which postulates that the complexity of an organism's social environment has imposed selective pressures on brain evolution. This leads us to hypothesize that special neural mechanisms might underlie the processing and memory of social cues. In this project, we lay the foundation to explore how oxytocin (OT) facilitates social memories, using in vivo electrophysiological methods for the first time in prairie voles. This project also employs advanced behavioral methods such as automated video tracking and synchronized neural data logging. We collaborate with Dr. Larry Young's lab to elucidate the electrophysiological basis for how information processing of social cues is affected by social reward. In particular, how are oxytocin-sensitive brain areas that are implicated in social bonding functioning together during actual social interactions to facilitate bonding?
Some have hypothesized that the ultrasonic vocalizations of male mice act as a courtship signal to female mice. Indeed, these calls do have acoustic structure resembling birdsongs. However, we do not yet know how female mice respond to these calls. This is the question that our pilot study has begun to explore.
The BTBR mouse has been proposed as a potential model for autism spectrum disease. BTBR mice do exhibit deficits in communication-related and maternal behaviors. In collaboration with Jacqueline Crawley's group at the NIH, which performs the behavioral studies on these mice, we have conducted hearing assessments using auditory brainstem response (ABR) measurements.
Our lab utilizes a variety of techniques, including single-unit and local field potential electrophysiology in awake rodents (mice and prairie voles), multielectrode array electrophysiology, immunohistochemistry, fluorescent in situ hybridization and behavioral analysis. We also make extensive use of computational methods to analyze and model neural data. Our work walks a fine line between developing quantitative engineering approaches and asking novel biological questions.
Key words: neural coding, auditory processing, communication, cortex, neuroethology, maternal behavior, computational neuroscience, sensory systems, neural mechanisms of social communication, learning and memory, electrophysiology, behavior, molecular