Dendritically released transmitters cooperate via autocrine and retrograde actions to inhibit afferent excitation in rat brain

Abstract

Oxytocin is released from supraoptic magnocellular neurones and is thought to act at presynaptic receptors to inhibit transmitter release. We now show that this effect is mediated by endocannabinoids, but that oxytocin nonetheless plays an important role in endocannabinoid signalling. WIN55,212-2, a cannabinoid receptor agonist, mimicked the action of oxytocin and occluded oxytocin-induced presynaptic inhibition. The cannabinoid action is at the presynaptic terminal as shown by alteration in paired pulse ratio, a reduction in miniature EPSC frequency and immunohistochemical localization of CB 1 receptors on presynaptic terminals. AM251, a CB 1 receptor antagonist, blocked both the WIN55,212-2 and the oxytocin-induced presynaptic inhibition of EPSCs. Depolarization of postsynaptic magnocellular neurones (which contain fatty acid amide hydrolase, a cannabinoid catabolic enzyme) caused a transient inhibition of EPSCs that could be blocked by both the AM251 and Manning compound, an oxytocin/vasopressin receptor antagonist. This indicates that somatodendritic peptide release and action on previously identified autoreceptors facilitates the release of endocannabinoids that act as mediators of presynaptic inhibition.

Integration of Asynchronously Released Quanta Prolongs the Postsynaptic Spike Window

“…Asynchronous release is not dependent on postsynaptic cell phenotype Oxytocin (OT) MNCs can release OT (Moos et al, 1989;Brussaard et al, 1996;Kombian et al, 1997;Ludwig et al, 2002;Sabatier et al, 2003) and endocannabinoids (Hirasawa et al, 2004;Oliet et al, 2007) from their dendrites. Likewise, vasopressin (VP) cells can release VP (Pow and Morris, 1989) or dynorphin (Watson et al, 1982).…”

Oxytocin as a natural antipsychotic: a study using oxytocin knockout mice

“…While peripheral Oxt release is important during parturition and lactation, central Oxt release can affect maternal behavior and learning and memory. [18][19][20][21][22] In patients diagnosed with either schizophrenia or obsessive compulsive disorder, there have been reports of elevated Oxt baseline concentrations in cerebral spinal fluid (CSF) in some, 23,24 but not all, 25 studies. Rats treated with antipsychotics have elevated Oxt secretion, 26 suggesting that endogenous Oxt may be important for the effects of antipsychotic drugs.…”

Dual Regulation of Anterograde and Retrograde Transmission by Endocannabinoids

“…Numerous molecules, including lipid precursors, amino acids, and neuropeptides, have been identified as retrograde transmitters, raising the intriguing possibility that multiple retrograde signals originate from a single postsynaptic neuron. While the concept of anterograde cotransmission is widely accepted (Kupfermann, 1991;Weisskopf et al, 1993;Jonas et al, 1998;Jo and Schlichter, 1999;Lu et al, 2008;Tecuapetla et al, 2010), there are only a few examples of neurons coreleasing retrograde messengers (Duguid and Smart, 2004;Hirasawa et al, 2004;Zilberter et al, 2005;Di et al, 2009). Consequently, little is known about the specific conditions that would bias a neuron toward the release of a specific retrograde signal, what consequence each signal would have on synaptic strength, and what impact the release of one signal would have on the subsequent release of different signals.…”

“…MNCs, however, are also capable of releasing other molecules from their somatodendritic compartment, including nitric oxide, neuropeptides, and endocannabinoids (eCBs) (Bains and Ferguson, 1997;Hirasawa et al, 2004;Ludwig et al, 2005;Di et al, 2009). In this current study, we asked whether physiologically relevant bursts of spiking activity either in the absence of presence of synaptic activity, could drive the release of multiple retrograde transmitters from a single neuron and whether these different retrograde signaling molecules interact with one another to regulate synaptic strength.…”