Targeting Attentional Mechanisms in Tinnitus: Contribution of the Thalamic Cholinergic System
Abstract
Proposed experiments examine cholinergic attentional mechanisms in the auditory thalamus or medial geniculate body (MGB) using a sound-exposure rat model. The MGB is a key component in the brain~s tinnitus network, situated to gate the tinnitus sensation to the auditory cortex and limbic structures. Proposed experiments will characterize the nature and role of nicotinic cholinergic receptors (nAChRs) in MGB. Cholinergic projections to MGB, from the pedunculopontine tegmental nucleus (PPTg) are thought to modulate arousal and attention. Recently, it has been shown that increased bursting in MGB output neurons correlates with behavioral measures of tinnitus. Preliminary studies show tinnitus-related changes in the subunit makeup of nAChRs in MGB. The working hypothesis suggests that a phantom sound, without a physical correlate, and with related emotional involvement, results in increased activation of the PPTg. Novelty and limbic circuits inform the PPTg to ~pay attention,~ resulting in maladaptive activation of PPTg and hence, nAChRs in MGB. Consistent with this hypothesis, preliminary patch-clamp studies show cholinergic activation of presynaptic nAChRs on excitatory terminals which are blocked by an nAChR antagonist. Collectively preliminary studies suggest a role for nAChRs in MGB in the pathology of tinnitus.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 08, 2016
- Source ID
- N000141612306
Entities
People
- Donald M Caspary
Organizations
- Office of Naval Research
- Southern Illinois University
- United States Navy