The goal of my proposed research training is to explore the role of the amygdala in generating socially appropriate vocal responses to salient acoustic signals. The proposed experiments will identify the connections between the amygdala and the regions responsible for vocal production, the chemical messengers that convey signals along these pathways and the contributions of two distinct neural pathways to the initiation and shaping of vocal responses. Previous research demonstrates the importance of the amygdala in processing social stimuli but less is known about how this brain region generates the behavioral responses that are appropriate for a given social context. I will study this problem in a powerful model system (Xenopus laevis) in which vocal communication is well understood and the hindbrain vocal pattern generating circuit is mapped;distinctive fictive vocalizations can be evoked ex vivo facilitating neural circuit analyses. {{I have found that lesions of the central amygdala produce socially inappropriate vocal responses (as is the case for mammals), and that lesions of the bed nucleus of the stria terminalis produce deficits in the initiation of callig, frequently resulting in the lack of vocalization in response to social stimuli that normally induce calling. I will investigate the specific neural pathways involved in these two effects using neuroanatomical, electrophysiological and pharmacological techniques. The proposed experiments will address four specific aims. (1) Determine whether stimulation of the CeA is sufficient to induce answer calling. Electrical stimulation of the CeA will be used to initiate ficive answer calling from the excised brain (2) Identify the neurons in the CeA that project to the PbN and the BST. Dextran-conjugated dyes and confocal microscopy will determine which cells in the CeA project to the PbN and BST. Immunocytochemistry will determine whether they are GABAergic. (3) Determine whether disinhibition of PbN neurons is the mechanism through which the CeA produces answer calling. GABA agonists will be used to mimic input from the CeA in the isolated brain while recording fictive calling from the laryngeal nerve. (4) Determine whether stimulation of the BST initiates calling through a serotonergic mechanism. Serotonergic drugs will be used to block or facilitate fictive calling induced by electrical stimulation of the BST.}} By addressing these aims, this research will illuminate one of the fundamental functions of the amygdala, the generation of context-appropriate behavior. Further, it will contribute to a growing understanding of the role of the amygdala in social vocal behavior and could make important contributions to the treatment of communication disorders, such as speech aphasias, selective mutism, and stuttering, and social cognition disorders, such as Asperger's syndrome and autism spectrum disorders.

Public Health Relevance

The amygdala plays a role in processing complex sensory information for the purpose of action selection;individuals with damage to the amygdala show impairments in social cognition and individuals with autism or Asperger's display decreased amygdala activity when presented with socially relevant stimuli. Investigating the mechanisms through which the amygdala facilitates the initiation of speech and the production of contextually-appropriate social behavior could make an important contribution to the understanding of social communication disorders, such as speech aphasia, selective mutism, and stuttering, as well as social cognition disorders, such as Asperger's syndrome and autism spectrum disorders. Furthermore, exploring the functional connectivity of this network and the chemical signals necessary for normal communication may lead to innovations in the treatment of these diseases at the individual level.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM103266-01A1
Application #
8522585
Study Section
Special Emphasis Panel (ZRG1-F02B-M (20))
Program Officer
Janes, Daniel E
Project Start
2013-04-01
Project End
2013-09-30
Budget Start
2013-04-01
Budget End
2013-09-30
Support Year
1
Fiscal Year
2013
Total Cost
$82,205
Indirect Cost
Name
Columbia University (N.Y.)
Department
Biology
Type
Other Domestic Higher Education
DUNS #
049179401
City
New York
State
NY
Country
United States
Zip Code
10027
Hall, Ian C; Ballagh, Irene H; Kelley, Darcy B (2013) The Xenopus amygdala mediates socially appropriate vocal communication signals. J Neurosci 33:14534-48