Glycine receptor activation regulates short-term plasticity in CA1 area of hippocampal slices of rats

https://doi.org/10.1016/j.bbrc.2006.03.198Get rights and content

Abstract

Functional glycine receptors (GlyRs) are enriched in the hippocampus, but their roles in synaptic transmission are unclear. In this study, we examined the effect of GlyR activation on paired-pulse stimulation of the whole-cell postsynaptic currents (PSCs) in the Schaffer-CA1 synapses in rat hippocampal slices. Bath application of glycine reduced the amplitude of PSCs, accompanied by an increase in holding current and resting conductance. Moreover, glycine application increased the paired-pulse ratio (PPR) of PSCs significantly, an effect largely abolished by the GlyR specific antagonist strychnine. Interestingly, glycine application had no significant effect on either the amplitude or the PPR of excitatory postsynaptic currents (EPSCs). Our findings suggest that GlyR activation regulates hippocampal short-term plasticity by altering GABAergic neurotransmission.

Section snippets

Materials and methods

The care and use of animals for these experiments followed the guidelines and protocols approved by the Institutional Animal Care and Use Committee of Institute of Neuroscience, Shanghai Institutes for Biological Sciences, the Chinese Academy of Sciences.

Preparation of slices. Wistar rats (14 to 21 days old) were decapitated, brains were quickly removed and 400 μm coronal hippocampal slices were cut in well-oxygenated ice-cold artificial cerebrospinal fluid (ACSF) using a vibratome, as

Glycine application increased PPR of PSCs

Postsynaptic currents were recorded from CA1 pyramidal neurons of hippocampal slices using the whole-cell patch–clamp technique. During the recording, a hyperpolarizing pulse (−5 mV) was employed to monitor the membrane conductance changes. The experiments were performed at −70 mV in the presence of Mg2+ to block the N-methyl-d-aspartate (NMDA) receptor-induced responses. Two consecutive stimuli were performed at IPI of 50 ms to study short-term plasticity.

To study the function of hippocampal

Discussion

In the present study, we have demonstrated that activation of GlyRs in CA1 area of rat hippocampal slices increases the PPR of PSCs induced by two consecutive stimuli, which depends on intact GABAAR activity. Our results reveal a possible role of GlyRs in hippocampal short-term plasticity through their influence on GABAAR-mediated synaptic currents.

GABAergic inhibition has been implicated in hippocampal short-term plasticity [22]. For example, the PPD of field potentials could be induced by

Acknowledgments

This study was supported by the National Basic Research Program of China (No. 2006CB500803) and the National Natural Science Foundation of China (Nos. 30125015 and 30321002) to T.-L. Xu. We thank Dr. B. Robertson for comments on the manuscript, and N. Gong for technical assistance.

References (26)

  • L. Danglot et al.

    Morphologically identified glycinergic synapses in the hippocampus

    Mol. Cell Neurosci.

    (2004)
  • S.C. Chattipakorn et al.

    Strychnine-sensitive glycine receptors depress hyperexcitability in rat dentate gyrus

    J. Neurophysiol.

    (2003)
  • S.C. Chattipakorn et al.

    Pharmacological characterization of glycine-gated chloride currents recorded in rat hippocampal slices

    J. Neurophysiol.

    (2002)
  • Cited by (18)

    • Alcohol and the dopamine system

      2024, International Review of Neurobiology
    • Cross-talk pattern between GABA<inf>A</inf>- and glycine-receptors in CNS neurons is shaped by their relative expression levels

      2020, Brain Research
      Citation Excerpt :

      In the higher regions in the CNS, such as hippocampus and cortex, both GABAARs and GlyRs are expressed in the same neuron, but only GABAARs mediates fast inhibitory synaptic transmission. Glycine could be released and diffused from a specific set of neurons, astrocytes or blood vessels to GABAergic synapses, and thus constrains the strength of GABAergic synapses or regulates short-term plasticity (Zhang et al., 2006) through GlyRs-GABAARs cross-talk. The experimental protocols were approved by the Animal Care and Use Committee of the University of Science and Technology of China.

    • Fluoxetine inhibition of glycine receptor activity in rat hippocampal neurons

      2008, Brain Research
      Citation Excerpt :

      In the mature rat hippocampus, which expresses functional extrasynaptic GlyRs, there is increasing evidence that these extrasynaptic receptors play important roles in maintaining the normal excitatory balance for proper CNS function under physiological and/or pathological conditions (Chattipakorn and McMahon, 2003; Mitchell and Silver, 2003; Song et al., 2006; Zhang et al., 2008, 2006). Activation of GlyRs suppresses neuronal excitation and seizure-like events in the rat entorhinal cortex and hippocampus (Chattipakorn and McMahon, 2003; Kirchner et al., 2003; Song et al., 2006; Zhang et al., 2008, 2006). Meanwhile, the potent convulsant agent strychnine (STN) selectively antagonizes the GlyR, demonstrating the importance of GlyRs in CNS seizure activity.

    View all citing articles on Scopus
    View full text