Functional implications of a patch/matrix-like compartmental organization in the mouse inferior colliculus

小鼠下丘斑块/矩阵状区室组织的功能意义

• 批准号: 10220679
• 负责人: Alexandria Marie Lesicko
• 金额: $ 7.31万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-06 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10220679
• 关键词: Acoustic Stimulation; Acoustics; Address; Affect; Anatomy; Architecture; Area; Auditory; Auditory area; Auditory system; Behavior; Behavioral; Brain; Calcium; Cell Nucleus; Cells; Chemicals; Cluster Analysis; Contralateral; Corpus striatum structure; Detection; Disease; Exhibits; Gap Junctions; Goals; Head; Hearing; Image; Individual; Inferior Colliculus; Ipsilateral; Label; Lateral; Locomotion; Measures; Medial geniculate body; Modality; Motor; Motor Cortex; Motor output; Mus; Neurons; Neurosciences; Optics; Output; Pathologic; Pathology; Pathway interactions; Performance; Population; Process; Rest; Role; Route; Schizophrenia; Signal Transduction; Somatosensory Cortex; Sound Localization; Stains; Stimulus; Stream; Structure; System; Testing; Tinnitus; Training; Work; awake; calretinin; cell type; density; dorsal column; excitatory neuron; experimental study; gamma-Aminobutyric Acid; information processing; inhibitory neuron; insight; motor behavior; multimodality; neurochemistry; optogenetics; response; segregation; somatosensory; sound; superior colliculus Corpora quadrigemina; two-photon

PROJECT SUMMARY A major unresolved question in systems neuroscience is whether specialized anatomical structures support specific functions in behavior. Therefore, this proposal will bridge the gap between anatomical circuit diagrams and their predicted functional roles. Specifically, it will address the functional consequences of the patch/matrix-like “modular” anatomical organization that has recently been characterized in the inferior colliculus. This acoustico-motor nucleus can be subdivided into modular regions, characterized by high density staining for GAD67 and other neurochemical markers, and extramodular regions that express calretinin. These neurochemical divisions also correlate with differences in connectivity; for example, modular regions of the lateral cortex receive input from somatosensory and motor structures, such as the dorsal column nuclei and somatosensory and motor cortices, while extramodular areas receive auditory inputs from the auditory cortex and other regions of the inferior colliculus. It is presently unknown whether this structural compartmentalization gives rise to segregated streams for distinct types of information processing, as is seen in the patch/matrix system in the striatum. Therefore, the goal of this proposal is to determine whether the modularity of the lateral cortex is conserved at the functional level, thus giving rise to complementary processing zones with distinct roles in acoustico-motor behavior. Two main hypotheses will be explored: 1) that auditory and somato-motor signals activate distinct populations of cells in the lateral cortex, and 2) that modular zones serve as somatosensory-driven gating regions for auditory information. These hypotheses will be tested using a combination of two-photon calcium imaging, clustering analysis, optogenetics, and behavior. Cells in modular and extramodular regions of the lateral cortex will be imaged in response to acoustic or somato-motor stimuli, and clustering analysis will be used to determine whether the populations of neurons activated by each modality form distinct groups. To determine whether somatosensory-recipient cells in modular regions of the lateral cortex gate auditory responses, this pathway will be selectively manipulated while mice perform a two- alternative unforced-choice sound localization task. The effect of optical activation and inhibition of the somatosensory inputs on sound detection behavior will be assessed. The experiments outlined above will further characterize the functional organization and behavioral relevance of the lateral cortex, which could have important implications for both normal and pathological hearing. Furthermore, these experiments may reveal generalizable principles regarding modular architectures, which could provide insights into other modular structures, such as the striatum.

项目总结