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Oxytocin suppresses the GABAergic synaptic input in supraoptic neurones from the rat
1Graduate School Neurosciences Amsterdam, Research Institute Neurosciences, Vrije Universiteit, Faculty of Biology, The Netherlands.
Abstract:
Oxytocin, acting as an autotransmitter, gives rise to release of calcium from intracellular store(s) within magnocellular neurons in the supraoptic nucleus (SON). A possible target for a rise in intracellular calcium is the GABAA receptor, since it is known that the functioning of this receptor may depend (directly) on the intracellular free calcium concentration. Therefore the effect of oxytocin on the GABAergic synaptic input in the SON was analyzed. In situ patch clamp recordings from individual neurons of the SON were performed. Spontaneously occurring, bicuculline sensitive GABAergic inhibitory synaptic currents (IPSCs) were pharmacologically isolated from the excitatory glutamatergic synaptic input. This isolated GABAergic synaptic input was spontaneously and tonically active, arising from both somatic as well as from dendritic synaptic contacts and operated a chloride conductance. Application of oxytocin during such recordings, strongly reduced the amplitude of the IPSCs in 73% of the recordings. This reduction was (i) completely reversed by washing, (ii) blocked by a specific oxytocin receptor antagonist, and (iii) observed in slices from both female and from male animals. Thus autotransmission involving disinhibition of magnocellular neurons may explain why oxytocin facilitates it own release.
Insights
Oxytocin acts as an autotransmitter, reducing GABAergic inhibition in the supraoptic nucleus. This disinhibition mechanism may explain how oxytocin facilitates its own release from magnocellular neurons.
Area of Science:
- Neuroscience
- Neuroendocrinology
Background:
- Oxytocin is released from magnocellular neurons in the supraoptic nucleus (SON).
- Oxytocin may act as an autotransmitter, influencing neuronal function via intracellular calcium release.
- GABAergic receptor function is sensitive to intracellular calcium levels.
Purpose of the Study:
- To investigate the effect of oxytocin on GABAergic synaptic input in the SON.
- To determine if oxytocin modulates inhibitory neurotransmission in magnocellular neurons.
Main Methods:
- In situ patch clamp recordings were performed on individual SON neurons.
- GABAergic inhibitory synaptic currents (IPSCs) were pharmacologically isolated.
- The effects of oxytocin application were analyzed.
Main Results:
- Oxytocin significantly reduced the amplitude of isolated GABAergic IPSCs in 73% of recorded neurons.
- This reduction was reversible upon washout and blocked by an oxytocin receptor antagonist.
- The effect was observed in both male and female animals.
Conclusions:
- Oxytocin acts as an autotransmitter in the SON, reducing GABAergic synaptic input.
- This oxytocin-induced disinhibition of magnocellular neurons likely facilitates its own release.
- Autotransmission provides a feedback mechanism for regulating oxytocin secretion.