Differential expression of group I metabotropic glutamate receptors in functionally distinct hippocampal interneurons - PubMed (original) (raw)

Differential expression of group I metabotropic glutamate receptors in functionally distinct hippocampal interneurons

J A van Hooft et al. J Neurosci. 2000.

Abstract

Metabotropic glutamate receptors (mGluRs) have been proposed to be involved in oscillatory rhythmic activity in the hippocampus. However, the subtypes of mGluRs involved and their precise distribution in different populations of interneurons is unclear. In this study, we combined functional analysis of mGluR-mediated inward currents in CA1 oriens-alveus interneurons with anatomical and immunocytochemical identification of these interneurons and expression analysis of group I mGluR using single-cell reverse transcription-PCR (RT-PCR). Four major interneuron subtypes could be distinguished based on the mGluR-mediated inward current induced by the application of 100 microm trans-(1S,3R)-1-aminocyclopentane-1, 3-dicarboxylic acid (ACPD) under voltage-clamp conditions and the action potential firing pattern under current-clamp conditions. Type I interneurons responded with a large inward current of approximately 224 pA, were positive for somatostatin, and the majority expressed both mGluR1 and mGluR5. Type II interneurons responded with an inward current of approximately 80 pA, contained calbindin, and expressed mainly mGluR1. Type III interneurons responded with an inward current of approximately 60 pA. These interneurons were fast-spiking, contained parvalbumin, and expressed mainly mGluR5. Type IV interneurons did not respond with an inward current upon application of ACPD, yet they expressed group I mGluRs. Activation of group I mGluRs under current-clamp conditions increased spike frequency and resulted in rhythmic firing activity in type I and II, but not in type III and IV, interneurons. RT-PCR results suggest that activation of mGluR1 in the subsets of GABAergic interneurons, classified here as type I and II, may play an important role in mediating synchronous activity.

PubMed Disclaimer

Figures

Fig. 1.

Fig. 1.

Distinct interneurons respond differentially to application of 100 μ

m

ACPD. A, Bath application of 100 μ

m

ACPD evoked a slow, oscillatory inward current in voltage-clamped stratum oriens–alveus interneurons. Local application of ACPD evoked an inward current with similar amplitude but with faster time course. B, Histogram of the amplitudes of ACPD-evoked inward currents in stratum oriens–alveus interneurons (n = 96). Interneurons not responding to application of ACPD have not been included in the histogram. Gaussian curves were drawn to illustrate the existence of two populations. C, Inward currents evoked with 100 μ

m

ACPD and evoked action potential firing (150 pA, 1 sec) in the four types of interneurons. All ACPD-induced currents were recorded in the presence of 1 μ

m

TTX.

Fig. 2.

Fig. 2.

Type I and type III interneurons are O-LM cells and basket cells, respectively. A, Camera lucida reconstruction of functionally characterized, biocytin-filled type I and type III interneurons. Gray boxes indicate axonal arborization zones. B, Biocytin-filled interneuron, stained with avidin-FITC and in situ hybridization for somatostatin. Arrow indicates the biocytin-filled cell.C, Biocytin-filled interneuron, stained with avidin-FITC and immunostaining for parvalbumin on the same cell. Scale bars, 20μm.

Fig. 3.

Fig. 3.

Type II and type IV interneurons represent a heterogeneous population of interneurons. Camera lucida reconstructions of functionally characterized, biocytin-filled interneurons are shown.Gray boxes indicate axonal arborization zones.

Fig. 4.

Fig. 4.

The ACPD-induced inward current is mediated by postsynaptic group I mGluRs. A, Inward currents evoked with 100 μ

m

ACPD in a type I interneuron in the presence of 1 μ

m

TTX (left) and after 2 min of superfusion with a cocktail of antagonists of NMDA receptors (AP-5), AMPA receptors (CNQX), GABAA receptors (picrotoxin), and presynaptic mGluRs (MPPG) (right). B, Summary of the amplitudes of the inward currents evoked with ACPD (30 and 100 μ

m

) and the selective group I mGluR agonist DHPG (100 μ

m

) in type I, II, and III interneurons. The_number_ in parentheses indicates the number of cells (ND, not determined). C, The ACPD-evoked inward current in a type I interneuron is completely blocked after 2 min of superfusion with 1 m

m

of the nonselective mGluR antagonist MCPG. The selective group I mGluR antagonist_S_-4-CPG (300 μ

m

) blocks the ACPD-evoked inward current to 19.0 ± 1.7% (n = 3) of control.

Fig. 5.

Fig. 5.

Single-cell RT-PCR analysis of the presence of mGluR1 and mGluR5 mRNA in oriens–alveus interneurons.A, Ethidium bromide-stained gel of PCR products obtained from the four different cell types, as indicated _above_the panel. The arrow indicates the expected size of the PCR product (344 bp). B, Southern blot of the gel shown in A, hybridized with mGluR1- and mGluR5-specific oligonucleotide labeled probes. C, Summary of the single-cell RT-PCR results for the four different cell types. Bars represent the number of cells positive for mGluR1, mGluR5, or both mGluR1 and mGluR5, expressed as percentage of the total number of cells analyzed.

Fig. 6.

Fig. 6.

Activation of group I mGluRs induces rhythmic action potential firing in type I and II, but not in type III and IV, interneurons. A, Spontaneous action potentials recorded from a type I and type III interneuron in the absence and presence of 100 μ

m

ACPD. Note that the spike frequency of the type I interneuron is increased. B, Summary of the change in spike frequency in the presence of 100 μ

m

ACPD. The values for type III and IV interneurons (−10 ± 30 and 40 ± 80%, respectively; n = 4) are not significantly different from zero (p > 0.05).C, Autocorrelograms of stretches of action potential firing, as shown in A, recorded under control conditions and 10 sec after application of 100 μ

m

ACPD.

Similar articles

Cited by

References

    1. Ali AB, Thomson AM. Facilitating pyramid to horizontal oriens-alveus interneurone inputs: dual intracellular recordings in slices of rat hippocampus. J Physiol (Lond) 1998;507:185–199. - PMC - PubMed
    1. Bashir ZI, Bortolotto ZA, Davies ZH, Berretta N, Irving AJ, Seal AJ, Henley JM, Jane DE, Watkins JC, Collingridge GL. Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors. Nature. 1993;363:347–350. - PubMed
    1. Baude A, Nusser Z, Roberts JDB, Mulvihill E, McIlhinney RAJ, Somogyi P. The metabotropic glutamate receptor (mGluR1α) is concentrated at perisynaptic membrane of neuronal subpopulations as detected by immunogold reaction. Neuron. 1993;11:771–787. - PubMed
    1. Boddeke HWGM, Best R, Boeijinga PH. Synchronous 20 Hz rhythmic activity in hippocampal networks induced by activation of metabotropic glutamate receptors in vitro. Neuroscience. 1997;76:653–658. - PubMed
    1. Buhl EH, Halasy K, Somogyi P. Diverse sources of hippocampal unitary inhibitory postsynaptic potentials and the number of synaptic release sites. Nature. 1994;368:823–828. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources