Regulation of spontaneous phasic firing of rat supraoptic vasopressin neurones in vivo by glutamate receptors.

Endocannabinoids (eCBs) are feedback messengers in the nervous system that act at the presynaptic nerve terminal to inhibit transmitter release. Here we report that in brain slices from rat, eCBs are released from vasopressin (VP) neurons in the paraventricular nucleus of the hypothalamus following coincident bursts of presynaptic and postsynaptic spiking. eCBs transiently depress glutamate release from excitatory terminals and, in doing so, prevent the synapses from undergoing long-term depression (LTD). Specifically, we show that blockade of CB1 receptors unmasks LTD following coincident presynaptic and postsynaptic activity. This LTD is presynaptic in nature, but requires the release of the opioid peptide dynorphin from the postsynaptic neuron. Dynorphin release and subsequent LTD require the activation of postsynaptic metabotropic glutamate receptors (mGluRs). Our findings indicate that eCBs, by transiently depressing glutamate release, limit mGluR activation and indirectly gate release of dynorphin from the postsynaptic neuron. We propose that eCBs, in addition to their well described role in the rapid modulation of transmitter release from the nerve terminal, also regulate the release of other retrograde transmitters and thus encode for multiple temporal windows of synaptic plasticity.

Section: Resultsmentioning

confidence: 99%

Dual Regulation of Anterograde and Retrograde Transmission by Endocannabinoids

Iremonger

Kuzmiski²,

Baimoukhametova³

et al. 2011

“…The current data suggest that dendritically released dynorphin also curtails MNC excitability by inhibiting both spontaneous and action potential-dependent glutamate release. Since bursting in these cells requires excitatory synaptic drive (Nissen et al, 1995;, this would be a very efficient mechanism to control firing and hence hormone secretion into the blood. .…”

Section: Physiological Significancementioning

confidence: 99%

“…Blocking -opioid receptors in vivo dramatically increases the excitability of MNCs (Wells and Forsling, 1991;Brown et al, 1998), indicating an ongoing and important role for dynorphin in regulating the output of this network. Since spiking in MNCs in vivo, both tonically (Nissen et al, 1995) and in response to physiological stimuli , is dependent on excitatory, glutamatergic synaptic inputs, we hypothesized that the retrograde modulation of glutamate neurotransmission by dynorphin would be an efficient way for MNCs to control their own activity. Since MNCs are targeted by glutamate synapses that exhibit a high rate of stochastic, action potential independent release, we hypothesized that dynorphin should inhibit both spontaneous and action potential-dependent neurotransmission.…”

Section: Introductionmentioning

confidence: 99%

Retrograde Opioid Signaling Regulates Glutamatergic Transmission in the Hypothalamus

Iremonger¹,

Bains²

2009

Opioid signaling in the CNS is critical for controlling cellular excitability, yet the conditions under which endogenous opioid peptides are released and the precise mechanisms by which they affect synaptic transmission remain poorly understood. The opioid peptide dynorphin is present in the soma and dendrites of vasopressin neurons in the hypothalamus and dynamically controls the excitability of these cells in vivo. Here, we show that dynorphin is released from dendritic vesicles in response to postsynaptic activity and acts in a retrograde manner to inhibit excitatory synaptic transmission. This inhibition, which requires the activation of -opioid receptors, results from a reduction in presynaptic release of glutamate vesicles. The opioid inhibition is downstream of Ca 2ϩ entry and is likely mediated by a direct modulation of presynaptic fusion machinery. These findings demonstrate that neurons may self-regulate their excitability through the dendritic release of opioids to inhibit excitatory synaptic transmission.

“…In fact, in vitro phasic discharge does not depend per se on synaptic input and can be maintained in explants in which synaptic inputs are significantly attenuated (Bourque and Renaud, 1984), but, more significantly, it can persist during a block of both excitatory and inhibitory synaptic input (Hatton, 1982;Bourque and Renaud, 1984) (C. Li and W. Armstrong, unpublished observations). However, it should also be noted that synaptic input appears to play a profound role in vivo, because phasic firing is inhibited by a block of NMDA or AMPA/kainate receptors (Nissen et al, 1995).…”

Section: Synaptic Inputmentioning

confidence: 99%

Burst Initiation and Termination in Phasic Vasopressin Cells of the Rat Supraoptic Nucleus: A Combined Mathematical, Electrical, and Calcium Fluorescence Study

Roper¹,

Callaway²,

Armstrong³

2004

Vasopressin secreting neurons of the rat hypothalamus discharge lengthy, repeating bursts of action potentials in response to physiological stress. Although many electrical currents and calcium-dependent processes have been isolated and analyzed in these cells, their interactions are less well fathomed. In particular, the mechanism of how each burst is triggered, sustained, and terminated is poorly understood. We present a mathematical model for the bursting mechanism, and we support our model with new simultaneous electrical recording and calcium imaging data. We show that bursts can be initiated by spike-dependent calcium influx, and we propose that the resulting elevation of bulk calcium inhibits a persistent potassium current. This inhibition depolarizes the cell above threshold and so triggers regenerative spiking and further calcium influx. We present imaging data to show that bulk calcium reaches a plateau within the first few seconds of the burst, and our model indicates that this plateau occurs when calcium influx is balanced by efflux and uptake into stores. We conjecture that the burst is terminated by a slow, progressive desensitization to calcium of the potassium leak current. Finally, we propose that the opioid dynorphin, which is known to be secreted from the somatodendritic region and has been shown previously to regulate burst length and phasic activity in these cells, is the autocrine messenger for this desensitization.