Dendritically Released Peptides Act as Retrograde Modulators of Afferent Excitation in the Supraoptic Nucleus In Vitro

Abstract

Oxytocin (OXT) and vasopressin (VP) are known to be released from dendrites of magnocellular neurons. Here, we show that these peptides reduced evoked EPSCs by a presynaptic mechanism, an effect blocked by peptide antagonists and mimicked by inhibition of endogenous peptidases. Dendritic release of peptides, elicited with depolarization achieved by high frequency stimulation of afferents or with current injection into an individual neuron, induced short-term synaptic depression similar to that seen following exogenous peptide application and was prevented by peptide antagonists. Thus, dendritically released peptides depress evoked EPSCs in magnocellular neurons by activating presynaptic OXT and/or VP receptors. Such a retrograde modulatory action on afferent excitation may serve as a feedback mechanism to permit peptidergic neurosecretory neurons to autoregulate their own activity.

Somatodendritic Secretion in Oxytocin Neurons Is Upregulated during the Female Reproductive Cycle

“…Postsynaptic secretion of OT and adenosine inhibits presynaptic GABA release To test whether OT neurons secrete OT in the SON, and thereby reduce their own synaptic inhibition, we first stimulated OT neurons electrically with short trains of depolarizations [0 mV for 100 msec, 20 times at 2 Hz, in conformance with the protocol used by Kombian et al (1997)] and monitored sIPSC amplitude and frequency. For ethical reasons, we used juvenile male rats [postnatal day 21 (P21) to P28] in the first part of the study (Figs.…”

“…It is not likely that microdialysis would detect OT released from single neurons by single spikes within milliseconds after the spike. This detection is also hindered by endogenous protease activity, which breaks down extracellular OT (Kombian et al, 1997).…”

“…Oliet et al (2001) showed that regulation of synaptic release of glutamate within the SON is under control of metabotropic glutamate receptors and proposed that this type of retrograde signaling is sensitive to the extent of glial withdrawal. Thus, somatodendritic secretion of OT and adenosine may also be affected by changes in the configuration of the extracellular space and possible changes in endogenous protease activity (Kombian et al, 1997).…”

“…In this way, a positive feedback loop is created in which OT stimulates its own release within the SON (Neumann et al, 1993(Neumann et al, , 1994Lambert et al, 1994;Leng et al, 1999). However, to initiate electrical firing activity in OT neurons to release OT into the bloodstream, additional synaptic mechanisms are required (Kombian et al, 1997). During pregnancy, strong GABAergic inhibition prohibits the OT neurons from massive activation (Brussaard et al, 1997).…”

Endocannabinoid‐mediated short‐term synaptic plasticity: depolarization‐induced suppression of inhibition (DSI) and depolarization‐induced suppression of excitation (DSE)

“…These substances are able to modulate neurotransmitter release from afferent presynaptic terminals and include dopamine (Cheramy et al, 1981;Jaffe et al, 1998), dynorphin (Drake et al, 1994), glutamate and GABA (Zilberter et al, 1999;Zilberter, 2000), oxytocin and vasopressin (Kombian et al, 1997). Since they act in a direction which is opposite to that proposed by Cajal, they can be defined as 'retrograde messengers' (for a thorough review of retrograde signaling in the nervous system, see, Alger, 2002).…”