AMPAR-mediated Interictal Discharges in Neurons of Entorhinal Cortex: Experiment and Model.

The mechanisms of interictal discharges (IID) were studied under the conditions of the 4-aminopyridine model of spontaneous epileptiform activity in surviving rat brain slice preparations. Addition of the agents blocking GABA and NMDA receptors failed to inhibit IID generation in the entorhinal cortex. A mathematical model of IID has been developed on the basis of the excitatory neuron interaction mediated by the AMPA receptor. Short-term synaptic depression and slow afterspike-hyperpolarization are the key factors required to terminate a single IID. The IID shape-determining factors have been identified. The experimental and model IID features correspond to each other.

[INTERACTION OF GLUTAMATE AND GABA RECEPTORS IN THE CENTRAL NERVOUS SYSTEM].

The article provides an overview of postsynaptic interaction of GABA and glutamate receptors in central neurons. Co-localization of GABA and glutamate in synapses, structure and function of their receptors and interaction of both ionotropic and metabotropic glutamate and GABA receptors are being discussed.

[Modulation of GABA- and kainate-activated currents by metabotropic receptors in isolated rat cortical neurons].

Whole-cell patch-clamp recordings from isolated neurons from rat prefrontal cortex have been made to study GABAb and mGluR receptor modulation of currents induced by applications of GABA and kainate. The GABAb-receptor antagonist CGP-55845 (5 microM) enhanced the peak by 26 +/- 13% (n = 6) but had no effect on the steady-state of GABA-activated current. Bath application of GABAb-receptor agonist baclofen (50 microM) enhanced the GABAa currents by 9 +/- 2% (n = 8). Kainate-activated currents were not affected by baclofen. Both GABA-activated currents and kainate-activated currents were not affected by trans-ACPD (MGluR agonist). These results suggest that in cortex postsynaptic response of GABAa-receptors can be modulated by GABAb-receptors.

[Desensitization of glycine mediated currents in frog spinal cord neurons].

Whole-cell patch clamp recordings from isolated frog spinal cord neurons were made to study the desensitization of glycine-mediated currents. The decay phase of current induced by application of glycine (1 mM) could be either monoexponential or biexponential. Monoexponential decays had either tau1 = 1693 +/- 135 ms (n = 8) or tau2 = 364 +/- 42 ms (n = 9) time constants, while biexponential decays had both tau1 and tau2. Currents with fast monoexponential decay (tau2) remained reproducible through the experiment. Currents with slow monoexponential (tau1) and biexponential decay gradually became faster while whole-cell patch clamp recordings were being taken. These results suggest that, at least, two different glycine receptor subtypes are present in frog spinal cord neurons.

[Effect of GABA and glycine neuromediator interaction in the central nervous system].

Today it is well accepted that GABA can be co-localized and co-released with glycine in the same synapse. This article provides an overview of GABA and glycine co-localization and the effects of simultaneous activation of GABAA and glycine receptors. The review deals with mechanisms of direct and indirect receptor interaction, as well as with the effect of non-selective activation of glycine receptors by GABA.

[Summation of GABA- and glutamate-mediated currents in rat cortical neurons].

Whole-cell patch clamp recordings from isolated neurons from rat prefrontal cortex have been made to study the interaction of responses induced by application of GABA and glutamate. Two different pipette solutions were used in this research: the first one was based on CsCl, while the second one was CsF-based. With CsCl-based pipette solution being used, co-application of GABA (200 microM) and glutamate (200 microM) resulted in producing a total current smaller than the sum of the two individual responses. But with CsF-based pipette solution being used, the response to co-application of GABA (200 microM) and glutamate (200 microM) was equal to the sum of the two individual responses. These results suggest that there is a cross-modulation between GABA- and glutamate-mediated responses.

Characteristics and interaction of GABAergic and glycinergic processes in frog spinal cord neurons.

Whole-cell patch clamp recordings from isolated spinal cord neurons from the frog Rana temporaria were made to study the interaction of processes induced by application of GABA and glycine. The amplitudes of currents evoked by application of glycine did not change with time, while the amplitudes of GABA-mediated currents decreased two-fold during the first 15 min of the experiment and stabilized at the new level. Neuron responses to simultaneous application of GABA and glycine were always smaller than the sum of the responses to separate application of these neurotransmitters. On application of GABA and glycine at the same concentration (5 mM), the amplitude of the response to simultaneous application decreased with time, reaching the level of the glycine-mediated response. A mixture of glycine and GABA at 8 microM and 5 mM, respectively, gave settled responses which were larger than the largest individual response by more than obtained with other mixtures. These data provide evidence that frog motoneurons may express receptors activated by both GABA and glycine.

Differences in the activation of inhibitory motoneuron receptors in the frog Rana ridibunda by GABA and glycine and their interaction.

Intracellular recording of potentials was used in isolated spinal cord segments from the frog Rana ridibunda to compare the inhibitory effects of GABA and glycine on the motoneuron membrane. At equal concentrations, the response (a change in membrane potential) to application of glycine was 1.5-2 times greater than the response to GABA in terms of amplitude, and EC(50) values were 0.75 and 1.57 mM, respectively. The response to simultaneous application of GABA and glycine averaged 79.1 +/- 2.4% (n = 19) of the sum of the individual responses and 130.1 +/- 1.5% (n = 19) of the glycine response (partial occlusion). Preliminary application of glycine decreased the GABA response by 85.3 +/- 0.2% (n = 10), while preapplication of GABA decreased the glycine response by only 52.9 +/- 0.3% (n = 11). The glycine and GABA responses were specifically suppressed by strychnine and bicuculline. These results provide evidence that as in mammals, amphibian motoneurons have both glycine (predominantly) and GABA(A) receptors; they also show that asymmetrical cross inhibition can occur.

[Characteristics and interactions between glycine- and GABA-mediated responses of the frog spinal cord neurons].

Interactions between GABA and glycine receptors in dissociated neurons from the frog spinal cord lumbar enlargement were analyzed by using whole-cell patch-clamp technique. As the recordings were made without intracellular ATP, the amplitude of GABA-mediated response gradually decreased to about 50 % of its initial value. Co-application of saturating concentrations of GABA and glycine resulted in producing a total current much smaller than the sum of the two individual responses. The amplitude of the total current gradually decreased to the value of that of the glycine-mediated response. After the amplitude of GABA response got stabilized, the amplitude of current produced by co-application of 5 mM GABA and 8 microM glycine (EC50) turned out to be by 25 % larger than that of either of the individual responses and reached the level of about 80 % of their sum. These results suggest that the frog spinal cord neurons express a population of inhibitory amino acid receptors that can bind either glycine or GABA.

[Differences in activation of the motoneurone inhibitory receptors in a frog Rana ridibunda by GABA and glycine and their interaction].

The membrane potential responses evoked by GABA and glycine bath applications were studied intracellularly in the motoneurons of the isolated frog spinal cord. The amplitude of glycine-evoked responses was 1.5-2.0 larger than that of GABA-evoked response at the same concentration. EC50 were 0.75 mM and 1.57 mM for glycine and GABA, respectively. The amplitude of responses induced by the simultaneous applications of both agonists were 79.1 +/- 2.4% (n = 19) of the sum of individual responses and 130.1 +/- 1.5% (n = 19) of individual glycine-induced responses (partial occlusion). GABA-evoked responses were decreased by 85.3 +/- 0.2% (n = 10) as a result of glycine preliminary application while preapplication of GABA reduced glycine-evoked responses only by 52.9 +/- 0.3% (n = 11). Glycine- and GABA-evoked responses were selectively suppressed by strychnine and bicuculline, respectively. These results suggest that amphibian spinal motoneurones express (less specifically than those of mammals) both glycine (predominantly) and GABAA receptors, with asymmetric cross-inhibition possibly taking place in them.

Three types of inhibitory miniature potentials in frog spinal cord motoneurons: possible GABA and glycine cotransmission.

Miniature inhibitory postsynaptic potentials (mIPSP) of motoneurons in isolated frog spinal cord were recorded in conditions of blockade of the conduction of nerve spikes and ionotropic glutamate receptors (TTX, 1 microM, CNQX, 25 microM, D-AP5, 50 microM). Three types of mIPSP were identified: those with fast and slow time characteristics and mIPSP with two-component decays. Two-component mIPSP accounted for 8.7% of all selected responses, fast mIPSP for 64.5%, and slow mIPSP for 26.8%. Blockade of GABA(A) receptors with bicuculline (20 microM) led to decreases in the numbers of slow and two-component mIPSP and an increase in the number of mIPSP with fast kinetics. Strychnine (1 microM), a blocker of glycine receptors, led to a reduction in the number of fast receptors and an increase in the number of slow potentials. These data suggest that frog spinal cord motoneurons have three types of inhibitory mIPSP, mediated by GABA, glycine, and simultaneous release of these two transmitters from the same presynaptic terminals.

[Three types of miniature inhibitory potentiaes in the frog spinal cord motoneurons: the possibility of GABA and glycine co-release].

Miniature inhibitory postsynaptic potentials (mlPSPs) were recorded from motoneurons of the frog isolated spinal cord after blocking action potentials and ionotropic glutamate receptors (TTX 1 mcm: CNQX 25 mcm, D-AP5 50 mcm). Three types of mlPSPs were selected by their time characteristics) fast, slow and mlPSPs with two decay time constants. We classified 8.7% of mlPSPs as dual-component, 64.5% as fast mlPSPs, and 26.8% as slow mlPSPs. The GABA(A)R blocker bicuculline (20 mcm) diminished the number of the slow and dual-component events while the number of mlPSP with a fast kinetics was increased. The GlyR antagonist strychnine (1 mcm) reduced the frequency of fast mlPSPs and increased this parameter of slow mlPSPs. These data suggest existence of three different mlPSP groups distinguished by their kinetics and sensitivity to receptor antagonists: fast events mediated by glycine, slow events mediated by GABA and dual-component mlPSPs corresponding to glycine and GABA co-release.