Metabotropic glutamate receptors modulate feedback inhibition in a developmentally regulated manner in rat dentate gyrus

We investigated group II metabotropic glutamate receptor (mGluR) modulation of glutamatergic input onto hilar‐border interneurones and its regulation of feedback inhibition in the dentate gyrus. Selective activation of group II mGluRs with (2S,2′R,3′R)‐2‐(2′,3′‐dicarboxycyclopropyl)glycine (DCG‐IV) depressed mossy fibre (MF)‐evoked excitatory drive to these interneurones with significantly greater depression in juvenile than adult rats. During 20 Hz MF stimulus trains, EPSCs became depressed. Depression during the early, but not later part of the train was significantly greater in juvenile than adult rats and was blocked by the mGluR antagonist (2S)‐2‐amino‐2‐[(1S,2S)‐2‐carboxycycloprop‐1‐yl]‐3‐(xanth‐9‐yl) propanoic acid (LY341495). In dentate granule cells from juvenile rats polysynaptic feedback IPSCs, but not monosynaptic IPSCs, were strongly suppressed by DCG‐IV. DCG‐IV also suppressed feedback inhibition of perforant path‐evoked population spikes. In contrast, in adult animals DCG‐IV did not significantly depress feedback inhibition. During 20 Hz stimulus trains in juvenile animals the summation of polysynaptic, but not monosynaptic IPSCs was suppressed by synaptically activated group II mGluRs. Blockade of these mGluRs with LY341495 significantly increased the area and duration of the summated IPSC, causing greater feedback inhibition of granule cell firing. In contrast, in adult animals LY341495 did not alter feedback inhibition following the stimulus train. These findings indicate that group II mGluRs modulate excitatory drive to interneurones in a developmentally regulated manner and thereby modulate feedback inhibition in the dentate gyrus.

[1]  P. Somogyi,et al.  Distribution of GABAergic synapses and their targets in the dentate gyrus of rat: a quantitative immunoelectron microscopic analysis. , 1993, Journal fur Hirnforschung.

[2]  T. Freund,et al.  Differences between Somatic and Dendritic Inhibition in the Hippocampus , 1996, Neuron.

[3]  J. Daly,et al.  A RADIOISOTOPIC METHOD FOR MEASURING THE FORMATION OF ADENOSINE 3′,5′‐CYCLIC MONOPHOSPHATE IN INCUBATED SLICES OF BRAIN , 1969, Journal of neurochemistry.

[4]  B. McNaughton,et al.  Spatial selectivity of unit activity in the hippocampal granular layer , 1993, Hippocampus.

[5]  G. Buzsáki,et al.  Inhibitory CA1-CA3-hilar region feedback in the hippocampus. , 1994, Science.

[6]  P. Conn.  Physiological Roles and Therapeutic Potential of Metabotropic Glutamate Receptors , 2003, Annals of the New York Academy of Sciences.

[7]  Dennis A. Turner,et al.  Interneurons of the Dentate–Hilus Border of the Rat Dentate Gyrus: Morphological and Electrophysiological Heterogeneity , 1997, The Journal of Neuroscience.

[8]  P. Somogyi,et al.  Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons , 1995, Nature.

[9]  Charles L. Wilson,et al.  Hippocampal and Entorhinal Cortex High‐Frequency Oscillations (100–500 Hz) in Human Epileptic Brain and in Kainic Acid‐Treated Rats with Chronic Seizures , 1999, Epilepsia.

[10]  C. Stevens,et al.  Heterogeneity of Release Probability, Facilitation, and Depletion at Central Synapses , 1997, Neuron.

[11]  R. Dingledine,et al.  Reduced Excitatory Drive onto Interneurons in the Dentate Gyrus after Status Epilepticus , 2001, The Journal of Neuroscience.

[12]  G. Buzsáki,et al.  Interneurons of the hippocampus , 1998, Hippocampus.

[13]  G. Finnerty,et al.  9-16 Hz oscillation precedes secondary generalization of seizures in the rat tetanus toxin model of epilepsy. , 2000, Journal of neurophysiology.

[14]  R. Anwyl,et al.  Presynaptic inhibitory action of the group II metabotropic glutamate receptor agonists, LY354740 and DCG-IV. , 1998, European journal of pharmacology.

[15]  P. Ornstein,et al.  LY341495 is a nanomolar potent and selective antagonist of group II metabotropic glutamate receptors , 1998, Neuropharmacology.

[16]  P. Somogyi,et al.  A High Degree of Spatial Selectivity in the Axonal and Dendritic Domains of Physiologically Identified Local‐circuit Neurons in the Dentate Gyms of the Rat Hippocampus , 1993, The European journal of neuroscience.

[17]  G. Buzsáki,et al.  Feed‐forward and feed‐back activation of the dentate gyrus in vivo during dentate spikes and sharp wave bursts , 1998, Hippocampus.

[18]  W. A. Wilson,et al.  GABAB autoreceptors mediate activity-dependent disinhibition and enhance signal transmission in the dentate gyrus. , 1993, Journal of neurophysiology.

[19]  J. Pin,et al.  Pharmacology and functions of metabotropic glutamate receptors. , 1997, Annual review of pharmacology and toxicology.

[20]  R. Dingledine,et al.  Differential regulation of synaptic inputs to dentate hilar border interneurons by metabotropic glutamate receptors. , 1998, Journal of neurophysiology.