Dissertation Defense = Lorraine Horwitz

“Novel Sensory Pathways for Thermosensation and Pain Under Physiological and Pathological Conditions”

Drs. Bo Duan and Susan Shore, Co-Chairs

ABSTRACT:

It is important to dissect the basic coding mechanisms of a sensory system to then understand the mechanisms by which sensory systems become dysregulated, leading to pathological conditions. For this talk, first I will explore the thermosensory system under physiological conditions to appreciate the basic mechanisms for sensory transmission underlying a specific neural circuit. Specifically, a population of excitatory interneurons co-expressing Caldinin1 and Lbx1 in the dorsal spinal cord that receives monosynaptic connections from TRPM8⁺ primary sensory neurons was identified, and plays a key role in the transmission of innocuous cool sensations. Next, I will describe the interactions between the auditory and nociceptive systems under pathological conditions. Loud noise exposure can lead to dysregulation of the auditory system resulting in several auditory disorders such as tinnitus, hearing loss, and hyperacusis. Hyperacusis is a particularly debilitating disorder that can be classified into loudness and affective types. It is important to use the appropriate animal model for each subtype of hyperacusis, however, currently there are very few animal models for affective hyperacusis. By developing novel animal models of affective hyperacusis we can begin to understand the underlying neuronal mechanisms of affective hyperacusis. Furthermore, hyperacusis is often comorbid with somatosensory disorders, therefore we tested the hypothesis that the auditory system interacts with the somatosensory system and found that all mice regardless of hyperacusis status developed mechanical allodynia. These results suggest that a single auditory insult can produce chronic nociceptive changes to not just the auditory but also the somatosensory systems. Taken together, these projects aid in our understanding of sensory coding mechanisms and the role of multisensory integration in the generation of chronic pain.