Activation of metabotropic glutamate receptors inhibits GABAergic transmission in the rat subfornical organ
Section snippets
Slice preparation and maintenance
The slices containing the SFO were prepared by the previously reported methods.28., 51. Sprague–Dawley rats (four to six weeks) were deeply anesthetized with ether and decapitated according to the protocol for care and use of animals approved by the Laboratory Animal Care Advisory Committee of Seoul National University. The brain was quickly dissected out, immersed in cold artificial cerebrospinal fluid (aCSF, 0–4°C), and aerated with O2/CO2 (95/5%). In each rat, one thin coronal slice
Spontaneous postsynaptic currents recorded from subfornical organ neurons
The results presented were based on a total of 70 SFO neurons successfully voltage-clamped at −70 mV. Fig. 1A illustrates a typical record of whole cell current showing a complete blockade of spontaneous synaptic currents by the bath-application of bicuculline (20 μM), a GABAA receptor antagonist. The respective cumulative distribution curves of the amplitude and inter-event intervals of spontaneous postsynaptic currents did not show inflections (Fig. 1A-a and A-b), indicating that the synaptic
Discussion
In this study we found that glutamate inhibited the synaptic release of GABA via activation of group II mGluRs on the axonal terminal of presynaptic GABAergic neurons and thereby could exert excitatory effects in the SFO. Evidence for the presynaptic inhibition of spontaneous inhibitory postsynaptic currents (sIPSCs) is that the frequency of sIPSCs was selectively reduced by glutamate without changing the amplitude and decay time-constant of sIPSCs (Fig. 2, Fig. 3). Evidence for the activation
Conclusion
We showed that activation of group II mGluRs on the axonal terminal suppresses the frequency of GABAA-receptor-mediated sIPSCs, the major synaptic activity in SFO neurons. Our results suggest that glutamate can excite SFO neurons by activation of presynaptic mGluRs as well as postsynaptic iGluRs. In view of the EC50 value of 47 μM for the inhibition of sIPSC frequency and the lack of the blood–brain barrier, presynaptic group II mGluRs are likely to be activated by circulating as well as
Acknowledgements
This work was supported by the Korea Ministry of Science and Technology under the Brain Science Research Program, and in part by the Brain Korea 21 Project.
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2021, Handbook of Clinical NeurologyCitation Excerpt :In further experiments with their rat in vitro SFO preparation, these authors used intracellular recordings to record the first action potentials from SFO neurons. Importantly, these early experiments indicated that SFO was not composed entirely of “sensory” neurons, which might project axons to other sites but instead contained projection neurons as well as both excitatory and inhibitory interneurons (Osaka et al., 1992; Lee et al., 2001). Anatomical studies using anterograde tracing (Miselis, 1981; Lind et al., 1982) suggested an efferent projection from SFO to supraoptic nucleus and paraventricular nucleus.
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