Neuromodulatory Mechanisms in the Auditory Tectothalamic Pathway
Rivera, Luis
2023
Abstract
How our brains identify and respond to speech and other auditory cues remains unclear. Neuromodulators, neurotransmitters known to affect the excitability of neurons by regulating processes such as neurotransmitter release from presynaptic terminals, are likely to modulate the excitability of neurons during sensory processing. In this dissertation, I aim to determine the roles and mechanisms of two distinct neuromodulators in two regions of the auditory pathway, the inferior colliculus (IC) and the medial geniculate (MG). My goal is to expand our knowledge on the role of neuromodulation in the auditory system. The IC, a hub for auditory processing located in the midbrain, contains neurons that exhibit selective responses to different features of speech and sounds. Previous findings suggest that acetylcholine (ACh), a neuromodulator associated with attention and synaptic plasticity, may provide an attention-based mechanism to alter auditory processing in the IC. Furthermore, neurons in the IC express different combinations of nicotinic acetylcholine receptor (nAChR) subunits, suggesting that the excitability of neurons in the IC can be altered by cholinergic signaling. However, the cellular-level mechanisms of cholinergic signaling in the IC remained unknown. In Chapter 2, I showed that VIP neurons in the IC are strongly modulated by ACh. By using whole-cell current clamp recording and pharmacology, I determined that the effect of ACh on VIP neurons is mediated by α3β4* nAChRs. These results present the first, cellular-level mechanism for cholinergic modulation of a specific neuron type in the IC and provide fundamental knowledge for in vivo studies exploring the role of ACh signaling during auditory learning and processing. The MG acts as the thalamic relay center of auditory information. It is a complex of nuclei that receives a combination of excitatory and inhibitory inputs from the IC. This region strongly expresses the receptors for the vasoactive intestinal peptide (VIP), a neuropeptide that can modulate intrinsic properties of neurons and even affect synaptic transmission. However, the effects of VIP on the excitability of MG neurons, and the sources of VIP signaling to the MG remained unknown. Recent studies showed that IC VIP neurons send direct projections to the MG. I hypothesized that IC VIP neurons provide direct VIP signaling to the MG, affecting the excitability of the neurons in the thalamus. By using electrophysiology, pharmacology, and in situ hybridization, I determined that VIP depolarizes MG neurons via the activation of VIP receptor 2 (VIPR2). Furthermore, by using retrograde tracing, I found that VIP neurons from both the IC and auditory cortex send long range projections to the MG, suggesting that the MG receives VIP signaling from different brain regions. These results provide the first evidence for VIP modulation in the MG and open the door to studying how differing neuromodulator sources affect the excitability of neurons during auditory processing. Lastly, in Chapter 4 I summarize the findings presented in this dissertation and provide insight on future experiments and approaches to further our understanding of the role of neuromodulators in the auditory pathway.Deep Blue DOI
Subjects
Neuromodulation in the auditory pathway Vasoactive Intestinal Peptide Acetylcholine Inferior Colliculus Medial Geniculate Electrophysiology
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