Temporal dissociation of the feedback effects of dendritically co-released peptides on rhythmogenesis in vasopressin cells

Vasopressin neurones fire action potentials in a rhythmic 'phasic' pattern, characterised by alternating periods of activity and silence. Vasopressin and dynorphin are co-packaged in neurosecretory vesicles that are exocytosed from vasopressin cell dendrites and terminals and both have been implicated in the generation of phasic activity patterning through autoregulatory mechanisms. Here, identified supraoptic nucleus vasopressin cells exhibiting spontaneous phasic activity were recorded from urethane-anaesthetised rats administered the V1 vasopressin receptor antagonist, OPC 21268, or the kappa-opioid receptor antagonist, nor-binaltorphimine. OPC 21268 elevated firing rate throughout each burst whereas nor-binaltorphimine excitation emerged over the course of each burst, indicating a progressive activation of kappa-opioid receptor mechanisms during bursts. To determine whether changes in post-spike excitability could account for these effects, we plotted the probability of action potential firing with time after the preceding action potential (hazard function) and found that, similarly to firing rate, this too was elevated by OPC 21268 throughout each burst whilst the excitatory effects of nor-binaltorphimine progressively increased over the course of each burst. Thus, the temporal organisation of the feedback effects of these co-released peptides is different, with vasopressin effectively causing an immediate reduction in overall excitability whilst dynorphin causes a progressive decrease in post-spike excitability over the course of each burst.