Bidirectional Control of Synaptic Transmission by Endocannabinoids from Corticotropin-Releasing Hormone Neurons
Jamieson, Bradley
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Jamieson, B. (2017). Bidirectional Control of Synaptic Transmission by Endocannabinoids from Corticotropin-Releasing Hormone Neurons (Thesis, Master of Science). University of Otago. Retrieved from http://hdl.handle.net/10523/7324
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Abstract:
The stress response is a physiological process which allows an organism to rapidly change its function in order to cope with a changing environment and maintain internal balance. The neuroendocrine stress response is initiated by excitation of corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus. Ultimately, CRH neuron excitability is controlled by upstream excitatory afferent neurons which form synaptic contacts onto them. The communication between these excitatory afferents and the CRH neurons is vital to the overall control of the stress response. Repetitive excitatory input to neurons causes the release of endocannabinoids (eCBs). eCBs are a retrograde messenger which act at the presynaptic cannabinoid type-1 receptor (CB1R) to inhibit further excitatory input onto neurons, by a process known as depolarisation-induced suppression of excitation (DSE). Here we show that following depolarisation of CRH neurons, there is a significant inhibition of evoked excitatory postsynaptic currents (n = 20, p < 0.05), reminiscent of the development of DSE. This response can also be blocked by inhibiting the CB1R, showing that it is, in fact, eCB-mediated. By inhibiting one specific pathway of eCB synthesis, we show that DSE is mediated by the eCB, 2-arachydonoyl glycerol (2-AG). Surprisingly, we note that, following depolarisation, eCBs can significantly increase the frequency of spontaneous excitatory synaptic currents onto CRH neurons when CB1Rs are inhibited (n = 10, p < 0.01). We have shown that this process is mediated by eCB action onto TRPV1 channels, and that this is not due to the release of 2-AG, but rather a different eCB. As oxytocin has been shown to stimulate the release of eCBs from neurons, we investigated whether oxytocin was able to inhibit currents onto CRH neurons. We have shown that there is a significant decrease in evoked excitatory postsynaptic currents following oxytocin application (n = 7, p < 0.01) and this response may be dependent on the CB1R.As such, we provide evidence for a functional interplay between eCBs, CRH neurons and oxytocin in regulating the stress response. We also show, for the first time, that depolarisation- induced release of eCBs is able to activate the TRPV1 channel to increase spontaneous currents onto CRH neurons.
Date:
2017
Advisor:
Iremonger, Karl; Herbison, Allan
Degree Name:
Master of Science
Degree Discipline:
Physiology
Publisher:
University of Otago
Keywords:
Corticotropin-Releasing Hormone; Endocannabinoid; CB1R; TRPV1; Oxytocin
Research Type:
Thesis
Languages:
English
Collections
- Thesis - Masters [3375]
- Physiology [154]