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 in mammals.
We address this problem by using a mouse model of acoustic communication. We use electrophysiological, computational, histological and behavioral methods to ask a variety of questions about how species-specific vocalizations are represented in the auditory cortex. How does the auditory system associate behavioral relevance with species-specific vocalizations? What neural circuits are involved, and how do they function in natural contexts? Are they genetically pre-wired or plastic, innate or experience-dependent? Answering these neuroethologically-inspired questions may give us insight into the neural basis and evolution of communication, and help elucidate mechanisms underlying auditory memories.
Functional Approach to Communication Sound Processing in Mouse Auditory Cortex
(Top) Ultrasonic calls emitted by mouse pups are simple, single frequency whistles with mild amplitude and frequency modulations.
(Bottom) Such calls elicit neural activity across low, middle and high frequency ranges of the anesthetized mouse auditory cortex. The timing of the onset and peaks in the mothers' response is better synchronized than in the virgin naives.
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? Using the communication between mouse pups and adult females (mothers and 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.
This project involves electrophysiology in awake mice, engineering-inspired analyses, and computational modeling of neural activity. Our neural coding studies involve analyzing both single unit as well as local field potential data, and have led us to develop new methods of analyzing population neural activity.
Mechanisms of Neuronal Activation and Plasticity by Sounds
Fluorescent labeling of nuclei in the auditory cortex.
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.
Modeling Synaptic Plasticity In Auditory Cortex (pilot)
Auditory cortical neurons often respond with either fast, transient or more delayed, sustained neural firing. These response types can be incorporated into an STDP model that reproduces some aspects of the neural differences between virgins and mothers.
If the differences between virgins and mothers are cortical in origin, then a possible mechanism is cortical synaptic plasticity. Using time courses of neural responses derived from single unit data, we can build a straightforward spike-timing-dependent synaptic plasticity (STDP) model that mirrors the spike timing changes observed in mothers. This project is purely computational.
Does Oxytocin Mediate Social Memories of Communication Vocalizations? (pilot)
CBN-funded pilot project.
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 pilot project, we explore whether oxytocin (OT), which is involved in the memory of social olfactory cues, also plays a memory role for social acoustic cues like mouse vocalizations. This project employs advanced behavioral methods such as automated video tracking and analysis, and is a collaboration with Larry Young's lab at Yerkes.
Communicative Significance of Mouse "Song" During Courtship (pilot)
Divided cage paradigm for investigating the role of mouse ultrasound vocalizations in courtship.
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.
Sensory Stimulation and Adult Neurogenesis in Mice (pilot)
Adult hippocampal neurogenesis originates from precursor cells in the adult dentate gyrus and results in new granule cell neurons. Regulation of this process is related to and dependent on environmental stimuli. Several studies showed a connection between adult neurogenesis and either enriched environments, stress or isolation. Positive social stimuli, such as communication sounds, might also regulate neurogenesis, but has not yet been studied in this context. This is the aim of a pilot study initated by visiting intern, Imke Kirste from Gerd Kempermann's lab at the Center for Regenerative Therapies, Dresden.
Hearing in BTBR mice (pilot)
Average tone-evoked ABR showing multiple peaks associated with synchronized activation of various brainstem and midbrain auditory nuclei.
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 electrophysiology in awake, restrained mice, 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