Joseph F. Bergan - US grants

[unreadable] DESCRIPTION (provided by applicant): A central challenge for neuroscience is determining how experience shapes the functional properties of the central nervous system. The auditory localization pathway in barn owls represents the associations of auditory cues with locations in space as neurophysiological maps. Previous research has shown that experience shapes these maps powerfully in juveniles, but has little effect in adults. Because of its exquisite precision, the auditory localization system has proven to be an excellent model for investigating the instructive role experience plays in determining neural function. The proposed research will employ behavioral, pharmacological, and electrophysiological techniques to investigate principles that govern auditory plasticity. Particular attention will be paid to techniques that increase plasticity in adults. Understanding the cellular mechanisms that underlie adaptive plasticity is an important step towards formulating optimal therapies for rehabilitation following injury to the central nervous system. [unreadable] [unreadable]

DESCRIPTION (provided by applicant): The vomeronasal system (VNS) detects important chemosensory cues in the local environment and transforms these cues into adaptive social behaviors. Despite myriad advances in our understanding of the cellular and molecular biology of the VNS, several essential questions remain unexplored, in particular concerning the electrophysiological properties of higher nuclei in the VNS. The studies described in this proposal are aimed at identifying neural computations occurring in the medial amygdala (MEA) that are critical for the transduction of sensory cues and generation of social behavior. Several convincing lines of anatomical, molecular, pharmacological, and behavioral evidence indicate that MEA neurons represent a critical stage for information processing within the VNS. The MEA receives sensory input from the accessory olfactory bulb, and is reciprocally connected with a network of nuclei essential for the production or social behaviors. The MEA is segregated into regions with distinct genetic expression patterns that delineate important functional segregations. For example, the posterior dorsal MEA (MEApd) is important for the detection of reproductive stimuli, while the posterior ventral MEA (MEApv) is specialized to detect defensive stimuli. Aromatase-expressing neurons, found in the MEApd but not in the MEApv, are sexually dimorphic in number and projection pattern, and are thought to underlie VNS mediated sexually dimorphic behaviors. The work outlined in the proposal will be performed over the next three years. The principle investigator will conduct the vast majority of the described experiments and data analyses. However, several key components of these experiments will be conducted in collaboration with members of the Dulac lab having relevant skill sets. Each aim of this proposal employs recording electrophysiological responses in the MEA while stimulating the VNS with ethologically important stimuli. Stimuli were chosen to encompass broad categories such as predators, mates, sympatric competitors, and kin. The purpose of the first specific aim is to systematically determine patterns of chemosensory responses present in the MEA. The second aim extends these findings by assigning specific response patterns to genetically defined populations of MEA neurons. The third aim, investigates the role of the MEA in guiding social behavior using electrophysiology in awake mice. These complimentary experimental approaches will provide important insights into the neural mechanisms that detect chemosensory cues and produce essential social behaviors. PUBLIC HEALTH RELEVANCE: Since aromatase inhibitors are rapidly becoming a first-line treatment for breast cancer, it is important to understand the normal function of aromatase signaling in the brain. The functional characterization of aromatase expressing neurons will likely provide important insights for the beneficial treatment of breast cancer.

Project Summary/Abstract: The central goal of this work is to identify the configurations of neural circuit anatomy and function that support social behavior in males and females. Social behavior requires efficient integration of sensory cues from the external environment with an animal's internal physiology and neuroendocrine state. These computations often vary such that a single social stimulus can elicit markedly different behaviors in male and female animals. Here, we seek to establish how unique patterns of circuit connectivity shape sexually dimorphic circuit function. We will focus on aromatase?expressing neurons and estrogen receptor alpha?expressing neurons in the extended amygdala. The mouse is an ideal species for revealing the contribution of genetically defined populations of neurons to social behavior. In people, sex differences in behavior likely arise from complex interactions of biology and past experiences, but our social behavior networks share a deep evolutionary history with other vertebrates. In mice, reproducible sex differences in the size of specific populations of neurons, patterns of gene expression, targets of axonal projections, and dendritic architecture are well-established. When paired with powerful tools for genetic manipulation, these populations of neurons provide a unique opportunity for a systematic investigation of the relationships between neuroanatomical variation (at the level of circuits) and sex differences in behavior. Because the specific circuit configurations for either target population are not yet known in males or females, Aim I will use rabies tracing to map these circuits with an eye toward quantifying sexually dimorphic wiring patterns. Aim II investigates the neurochemical phenotype of neurons that provide input to aromatase- expressing and estrogen receptor alpha?expressing neurons in the extended amygdala. Quantifying the neurotransmitters used in these circuits will help us understand how activity at one node influences activity in its synaptically coupled partners. Aim III explores the moment-to-moment activity of these neural populations to reveal their respective contributions to processing social stimuli and producing social behavior. Together, these studies will advance our mechanistic understanding of how social information is transformed into sexually dimorphic cognitive, endocrine, and behavioral outputs.