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URMC / Labs / Holt Lab / Projects / Efferent-Receptors-and-Synaptic-Mechanisms

Efferent Receptors and Synaptic Mechanisms

Examples of efferent neurons firing.

Distinct vestibular afferent classes respond differently to stimulation
of efferent neurons. Electrical stimulation of efferent fibers
can result in several different afferent responses depending on the
type of afferent. BT afferents respond with a pronounced inhibition
whereas CD afferents are profoundly excited. BM afferents show a mixed
response consisting of inhibition followed by excitation. The sites of
action for these efferent-mediated afferent responses are diagrammed above.

In reptiles, birds, and mammals, efferent vestibular neurons can provide synaptic input to three targets: type II hair cells, their bouton afferents, and afferent calyces innervating type I hair cells (Figure 1, upper panel). Stimulation of efferent neurons would be expected to exert their effects at one of these three locations. In our system, we have mainly focused on three classes of vestibular afferents and their different responses to efferent stimulation. These afferents differ in the kinds of hair cells that they innervate. BT and BM fibers innervate type II hair cells whereas CD afferents terminate on type I hair cells. When efferents are stimulated, BT afferents are profoundly inhibited, CD afferents are strongly excited, and BM afferents show mixed responses usually consisting of brief inhibition followed by excitation (lower panels of figure to right).

By using a number of pharmacological agents, we can deduce the locations and nature of the receptors involved in generating these different afferent responses. Vestibular efferent neurons contain acetylcholine (ACh), ATP, CGRP, and several opioid peptides. We hypothesize that the response of each afferent class to efferent stimulation is predominantly mediated by the activation of distinct ACh receptors and that ATP, CGRP, and the opioid peptides are anticipated to function in a neuromodulatory capacity by directly interacting with the cholinergic system. To test our hypotheses, pharmacological and immunohistochemical methodologies will be used to identify each ACh receptor and its downstream effectors in hair cells and afferents (see Efferent Synaptic Animation). Interactions with other efferent transmitters will also be identified.

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