A principal task of the auditory system is to process the temporal and intensity information contained in a sound stimulus, which it does by integrating excitatory and inhibitory input from different sources. The first nucleus in the central nervous system, where such integration occurs, is the inferior colliculus (IC). The IC is a brainstem nucleus. It receives direct input from most of the auditory nuclei in the brainstem and, in turn, provides nearly all of the input to the auditory forebrain. In addition to its importance in auditory processing, the IC is the site of origin of pathological hyperexcitability that leads to sound-evoked seizures. Despite its strategic location and extensive input convergence, the regulation of excitability by inputs and intrinsic neuronal properties has not been investigated, and the definition of a basic circuit in terms of defined classes of cells and connections is necessary to understand its function. We recently demonstrated that excitatory and inhibitory inputs to the IC selectively regulate gain control and neuronal excitability. This regulation of gain control determines how well neurons in the IC can code sound intensity. We have also found evidence for local excitatory recurrent circuits in the IC. Furthermore, activity is propagated in a complex fashion between the two sides of IC. We will combine electrophysiological recordings of activity in single neurons, optical monitoring of neuronal population responses with voltage-sensitve dyes and computational modeling techniques to address the following specific aims: 1. Determine how patterned synaptic input regulates the excitatory/inhibitory ratio in single IC neurons. 2. Determine the importance of cell type specificity in local and inter-collicular circuitry. 3. Determine the requirements for inter-collicular connectivity. Our results will delineate the constraints on excitability in the normal auditory system set by network and cellular components, and will further our understanding of the factors that lead to the hyperexcitable state that gives rise to epileptic seizures. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC008120-04
Application #
7383809
Study Section
Auditory System Study Section (AUD)
Program Officer
Platt, Christopher
Project Start
2006-04-01
Project End
2011-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
4
Fiscal Year
2008
Total Cost
$236,813
Indirect Cost
Name
Northeast Ohio Medical University
Department
Biology
Type
Schools of Medicine
DUNS #
077779882
City
Rootstown
State
OH
Country
United States
Zip Code
44272
Sivaramakrishnan, Shobhana; Lynch, William P (2017) Rebound from Inhibition: Self-Correction against Neurodegeneration? J Clin Cell Immunol 8:
Grimsley, Calum Alex; Green, David Brian; Sivaramakrishnan, Shobhana (2016) L-type calcium channels refine the neural population code of sound level. J Neurophysiol 116:2550-2563
Grimsley, Calum A; Sivaramakrishnan, Shobhana (2014) Postnatal developmental changes in the medial nucleus of the trapezoid body in a mouse model of auditory pathology. Neurosci Lett 559:152-7
Li, Ying; Davey, Robert A; Sivaramakrishnan, Shobhana et al. (2014) Postinhibitory rebound neurons and networks are disrupted in retrovirus-induced spongiform neurodegeneration. J Neurophysiol 112:683-704
Chandrasekaran, Lakshmi; Xiao, Ying; Sivaramakrishnan, Shobhana (2013) Functional architecture of the inferior colliculus revealed with voltage-sensitive dyes. Front Neural Circuits 7:41
Grimsley, Calum Alex; Sanchez, Jason Tait; Sivaramakrishnan, Shobhana (2013) Midbrain local circuits shape sound intensity codes. Front Neural Circuits 7:174
Sivaramakrishnan, Shobhana; Sanchez, Jason Tait; Grimsley, Calum Alex (2013) High concentrations of divalent cations isolate monosynaptic inputs from local circuits in the auditory midbrain. Front Neural Circuits 7:175