Auditory Information Processing in the Amygdala

Northeast Ohio Medical University, Rootstown OH

Investigators

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Abstract

Project Summary The long-term goal of this work is to improve the understanding of neural mechanisms that underlie acoustic communication. Our premise is that the amygdala, a brain region associated with emotional expression, plays a critical role in this process. The amygdala “decides” whether a vocal signal is significant (salient), and whether its valence is positive or negative using contextual information from the vocal sequence, other senses, the listener’s internal state, and prior experience. Through outputs to centers that activate rewarding or defensive behaviors, the amygdala orchestrates emotional responses that are appropriate for the received vocal communication signals and their context. The amygdala also modulates responsiveness to vocal signals through its projections to auditory cortex. In other words, the amygdala likely influences how we hear and respond to social vocalizations. The study tests three general hypotheses. 1) The basolateral amygdala (BLA) is composed of distinct circuits that are excited by and selective for vocalizations with positive or negative valence and which project to different target nuclei associated with rewarding or defensive behaviors. 2) The activity within these separate circuits depends on both the received vocal signals and internal state cues, potentially increasing or decreasing excitation or altering temporal response patterns. 3) These short-term factors feeding into computations by BLA neurons are affected by longer term factors that include experience with associated behaviors as well as sex and estrous state of females. In three Specific Aims, we will examine bases for selectivity, temporal response patterns, and contextual modulation of vocal responses. First, we will use both electrophysiology and calcium imaging to assess neuronal response strength, timing, and degree of selectivity to vocalizations, then relate these responses to specific output pathways. Second, we will utilize chronic calcium imaging to assess how experience, sex, and female estrous state affect BLA responses, including how these relate to output circuits. Third, we will test the hypothesis that a key neuromodulator— acetylcholine—enhances responsiveness and persistent firing in circuits associated with aversive vocal stimuli while suppressing activity in circuits associated with affiliative or rewarding vocal stimuli. We will use the normal hearing CBA/CaJ mouse strain with a well-understood acoustic communication system as well as a related, normal hearing ChAT-Cre mouse strain to manipulate the acetylcholine input to BLA neurons. The Specific Aims provide an interconnected approach to understand the mechanisms acting within the BLA that contribute to the analysis of meaning in social vocalizations and control of behavioral outputs. These mechanisms are important in acoustic communication because the amygdala is involved in disorders that result in an altered emotional response to speech, such as anxiety, schizophrenia, autism, and post-traumatic stress disorder. This work may also suggest how degeneration of the acetylcholine system of the basal forebrain, as occurs in Alzheimer’s disease, affects amygdala-mediated responses to emotional vocalizations.