Information processing in the auditory system involves a bidirectional flow of signaling. Acoustic signals that originate in the sensory peripher (i.e., inner ear) travel to the cerebral cortex and form the bottom-up pathway. Signals originating in the cortex are transmitted in the reverse direction and form the top-down pathway. While many anatomical and functional studies have focused on the bottom up pathway, the cellular properties and synaptic connectivity (or circuitry) of the top-down pathway remain largely unknown. This proposal focuses on the intrinsic properties and microcircuit architecture of auditory cortical neurons that project to the inferior colliculus (IC) in the auditory brainstem. Or preliminary results show that IC-projecting neurons are localized in two different cortical layers: layer 5B and layer 7. Through the combined use of retrograde labeling techniques and paired whole cell recordings we will characterize the intrinsic physiological properties of the neurons in these parallel top-down pathways. We will use laser- scanning photostimulation to determine the underlying microcircuit architecture of top-down corticocollicular neurons. Our preliminary results show that auditory corticocollicular neurons exhibit pronounced hyperpolarization-activated currents (Ih), which limits the ability of excitatory inputs to generate spiking outputs. Noradrenergic and other modulatory pathways regulate Ih, suggesting that the excitability of top-down pathways in the auditory system are modulated by brain state. Finally, with the aid of in vivo functional imaging we will determine the tonotopic dependence of microcircuit architecture in primary auditory cortex. This contribution is significant because it is the first sep in understanding the functional network basis for the genesis of top-down signals to the auditory system. The proposed approach is innovative, in our opinion, because combines anatomical identification of top-down auditory cortical neurons, electrophysiological characterization, microcircuit mapping and in vivo functional imaging techniques to understand the tonotopic organization of top-down circuits in the auditory cortex.

Public Health Relevance

Top-down pathways from the cortex play an important role in modulating subcortical processing of behaviorally relevant auditory signals. This proposal aims to understand the tonotopic organization of cortical physiology and circuitry underlying the generation of top-down signals to the inferior colliculus. This research will significantly contribte to the understanding of the integration and regulation of top-down signaling pathways in healthy and pathological auditory processing.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Small Research Grants (R03)
Project #
1R03DC012585-01
Application #
8365967
Study Section
Special Emphasis Panel (ZDC1-SRB-Y (32))
Program Officer
Platt, Christopher
Project Start
2012-06-06
Project End
2013-05-31
Budget Start
2012-06-06
Budget End
2013-05-31
Support Year
1
Fiscal Year
2012
Total Cost
$151,500
Indirect Cost
$51,500
Name
University of Pittsburgh
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213