Pre and post-synaptic pathways underlying the stress response in the adrenal medulla

Summary

This research project investigates the pre- and post-synaptic pathways in the adrenal medulla to understand how acetylcholine (ACh) and pituitary adenylate cyclase-activating polypeptide (PACAP) regulate hormone release during the 'fight-or-flight' stress response.

What they want

The project proposes three specific aims to understand how variations in presynaptic splanchnic input are translated by different receptor-coupled pathways in chromaffin cells to dynamically regulate hormone output. Aim 1 will define the role of Ca2+ sensing and synaptotagmin (Syt7) in synaptic facilitation at the splanchnic-chromaffin cell synapse using in situ slice electrophysiology. Aim 2 will investigate the requirement of Phospholipase C-epsilon (PLCε) for transducing PACAP stimulation into Ca2+ signals in chromaffin cells and its role in sustaining hormone output during increased splanchnic firing. Aim 3 will characterize PACAP-stimulated fusion pores and investigate mechanisms by which they are constrained, relevant for the differential release of biogenic amines and hormone peptides.

Deliverables

Definition of the role of Ca2+ sensing at the splanchnic-chromaffin cell synapse
Evaluation of Syt7's role in amplifying hormone discharge from chromaffin cells
Characterization of PLCε's requirement for transducing PACAP stimulation into Ca2+ signals in chromaffin cells
Investigation of PLCε activity's role in sustaining increases in hormone output
Characterization of properties of PACAP-stimulated fusion pores
Investigation of mechanisms by which PACAP-stimulated fusion pores are constrained
A coherent molecular and physiological framework for understanding the stress response

Technical requirements

in situ slice electrophysiology