Elsevier

Neuroscience

Volume 102, Issue 2, 15 January 2001, Pages 401-411
Neuroscience

Activation of metabotropic glutamate receptors inhibits GABAergic transmission in the rat subfornical organ

https://doi.org/10.1016/S0306-4522(00)00490-5Get rights and content

Abstract

Glutamate is known to increase neuronal excitability in the subfornical organ, a circumventricular organ devoid of the blood–brain barrier. To understand the synaptic mechanism of neuronal excitation by glutamate in this nucleus, we examined the effects of glutamate on GABAergic spontaneous inhibitory postsynaptic currents recorded from subfornical organ neurons in the rat brain slice. The baseline frequency, amplitude and decay time-constant of such spontaneous synaptic currents were 5.60 Hz, 119 pA and 17.3 ms, respectively. Glutamate (10–1000 μM) selectively inhibited the frequency of spontaneous GABAergic inhibitory postsynaptic currents (half-maximal effective concentration=47 μM) with little effects on their amplitudes and decay time constants. The inhibitory effect of glutamate on the frequency of spontaneous GABAergic postsynaptic currents was not blocked by tetrodotoxin (1 μM), or by the antagonists of ionotropic glutamate receptors. In contrast, such inhibitory effect of glutamate was mimicked by general or group II selective metabotropic glutamate receptor agonists such as DCGIV (2S,1′R,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine (half-maximal effective concentration=112 nM), but not by the agonists for group I or group III metabotropic glutamate receptors. Under current clamp mode, glutamate reduced the frequencies of spontaneous inhibitory postsynaptic potentials and action potentials in subfornical organ neurons.

Our data indicate that glutamate decreases the frequency of spontaneous inhibitory postsynaptic currents by acting on the group II metabotropic glutamate receptors on axonal terminals in the subfornical organ. From these results we suggest that the glutamate-induced modulation of tonic GABAergic inhibitory synaptic activity can influence the excitability of subfornical organ neurons.

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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