Potentiation Of Inhibitory Postsynaptic Currents Research Articles

Glycine blocks long-term potentiation of GABAergic synapses in the ventral tegmental area

The mesocorticolimbic dopamine system, originating in the ventral tegmental area (VTA) is normally constrained by GABA-mediated synaptic inhibition. Accumulating evidence indicates that long-term potentiation of GABAergic synapses (LTPGABA) in VTA dopamine neurons plays an important role in the actions of drugs of abuse, including ethanol.We previously showed that a single infusion of glycine into the VTA of rats strongly reduces ethanol intake for 24h. In the current study, we examined the effect of glycine on the electrophysiological activities of putative dopamine VTA neurons in midbrain slices from ethanol-naïve rats. We report here that a 15-min exposure to 10μM glycine prevented trains of high-frequency stimulation (HFS) from producing LTPGABA, which was rescued by the glycine receptor (GlyR) antagonist strychnine. Glycine also concentration-dependently decreased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs). By contrast, glycine pretreatment did not prevent potentiation of inhibitory postsynaptic currents (IPSCs) during a continuous exposure to the nitric oxide (NO) donor, SNAP (S-nitroso-N-acetylpenicillamine), or a brief exposure to 10μM glycine and 10μM NMDA (N-methyl-d-aspartate), an agonist of NMDA-type glutamate receptors. Thus, the blockade of LTPGABA by glycine is probably resulted from suppressing glutamate release by activating the GlyRs on the glutamatergic terminals. This effect of glycine may contribute to the reduction in ethanol intake induced by intra-VTA glycine observed in vivo.

Synaptic Neuronal Plasticity

Context: The current study aimed to review research articles concerning cortical representational plasticity following the manipulations of inputs. Evidence Acquisition: This review article compromised previous studies in PubMed, Google Scholar and Scientific Information databases according to the keywords since 1988. Results: CA1 neurons depolarization paired with CA3 presynaptic input result in EPSPs amplitude enhancement called LTP. Theta-burst stimulation of layer IV produced long term potentiation (LTP) in the granular primary motor cortex, but the agranular or primary somatosensory cortex was capable of generating LTP in case of GABAA receptor inhibition. Upper layers (UL)-induced, and White Matter WM-induced plasticity in layer VI corticogeniculate neurons were produced through type-5 metabotropic glutamate and N-methyl-D-aspartate (NMDA) receptors, respectively. Calcineurin and cannabinoid type 1 receptors are involved in WM-induced and UL-induced het-LTD, respectively. Long-term potentiation of inhibitory postsynaptic currents (IPSCs) was produced in FS-GABA neurons in layer II/III of the mouse visual cortex by tetanic activation. Conclusions: In summary, the current study presents rational evidences for specific fundamental forms of plasticity, containing associative long-term potentiation and depression of excitatory and inhibitory postsynaptic potentials.

Serotoninergic control of glycinergic inhibitory postsynaptic currents in rat hypoglossal motoneurons

This report presents the results of a study of the frequency potentiation of inhibitory postsynaptic currents (IPSCs) in hypoglossal motoneurons and its modulation by serotonin. A release-site model of synaptic plasticity was used to characterize the frequency-related potentiation of evoked IPSCs. Data were obtained to determine if the frequency potentiation of IPSCs occurs as a consequence of a low baseline quantal content of evoked IPSCs using whole cell patch-clamp recordings from hypoglossal motoneurons in the neonatal rat brainstem slice preparation. In these motoneurons, EPSCs and GABAergic IPSCs were blocked by the application of CNQX, AP-5 and bicuculline. Glycinergic IPSCs were evoked by threshold stimulation of inhibitory neurons in the nucleus of Roller, which is located ventro-lateral to the hypoglossal nucleus. IPSC responses to trains of stimuli were recorded in control solutions and in solutions containing serotonin, which is known to reduce IPSPs in this preparation. The amplitude of non-potentiated IPSCs was reduced and their frequency potentiation was enhanced when serotonin was added to the bath. These data were examined using a release-site model of synaptic plasticity in which facilitation is attributed to a time-dependent increase in the probability of transmitter release; depression is attributed to a time-dependent decrease in the number of sites available for release. Using this model, the effect of serotonin on frequency potentiation was explained by a combination of a reduction in the baseline probability of transmitter release and an increase in the time constant of decay of the increase in probability of release that follows a stimulus.

Developmental increase in asynchronous GABA release in cultured hippocampal neurons

Developmental changes in GABAergic synaptic transmission were examined in cultured hippocampal neurons using patch-clamp recordings and Ca 2+ imaging. In paired recordings, tetanization of the presynaptic GABAergic neuron with 80 pulses at either 40 or 80 Hz was accompanied by tetanic depression of inhibitory postsynaptic responses. In neurons that had been cultured for more than two weeks, asynchronous inhibitory postsynaptic currents often appeared during the tetanus and continued for several seconds following stimulation. There was little asynchronous activity in neurons that had been cultured for shorter times. However, no age-related changes were observed in the amplitude of single synchronous inhibitory postsynaptic currents, paired-pulse depression or post-tetanic potentiation of inhibitory postsynaptic currents. Following equimolar replacement of extracellular Ca 2+ with strontium ions (Sr 2+), single autaptic inhibitory postsynaptic currents were depressed in amplitude and asynchronous inhibitory postsynaptic currents were present on the decaying phase. Sr 2+-induced asynchronous inhibitory postsynaptic currents showed no dependence on age in culture. Imaging of Ca 2+ in single GABAergic boutons was performed by including Fluo-3 in the patch pipette. During action potential firing induced by stimulating at 80 Hz for 1 s, intracellular calcium [Ca 2+] i increased rapidly in individual boutons. Following the stimulus, [Ca 2+] i decayed back to baseline within 10–15 s. The half-time of decay increased from 1.7±0.2 s at 15 days in vitro to 4.0±0.2 s at 30 days in vitro ( P<0.05), with a developmental profile that closely matched the increase in asynchronous inhibitory postsynaptic currents. We propose that the increase in tetanus-induced asynchronous GABA-release during the first month of synapse maturation in vitro is caused by a slowing of the Ca 2+-clearing mechanisms in the GABAergic boutons. This results in larger and more prolonged elevations of [Ca 2+] i during tetanic stimulation, which leads to enhanced asynchronous transmitter release. We propose that the results of this study demonstrate a potentially important aspect of synapse maturation during development, and also imply that GABA release is up-regulated in conditions of decreased Ca 2+ buffering and clearing.