NPY Inhibits Glutamatergic Excitation in the Epileptic Human Dentate Gyrus

1999 ◽  
Vol 82 (1) ◽  
pp. 478-483 ◽  
Author(s):  
Peter R. Patrylo ◽  
Anthony N. van den Pol ◽  
Dennis D. Spencer ◽  
Anne Williamson
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
Granule Cells ◽  
Molecular Layer ◽  
Hippocampal Slices ◽  
Perforant Path ◽  
Cell Excitability ◽  
Metabotropic Glutamate ◽  
Normal Rat ◽  
Group 3 ◽  
Excitatory Responses

Neuropeptide Y (NPY) has been shown to depress hyperexcitable activity that has been acutely induced in the normal rat brain. To test the hypothesis that NPY can also reduce excitability in the chronically epileptic human brain, we recorded intracellularly from dentate granule cells in hippocampal slices from patients with hippocampal seizure onset. NPY had a potent and long-lasting inhibitory action on perforant path-evoked excitatory responses. In comparison, the group 3 metabotropic glutamate receptor agonistl-2-amino-4-phosphonobutyric acid (l-AP4) evoked a mild and transient decrease. NPY-containing axons were found throughout the hippocampus, and in many epileptic patients were reorganized, particularly in the dentate molecular layer. NPY may therefore play a beneficial role in reducing granule cell excitability in chronically epileptic human tissue, and subsequently limit seizure severity.

scholarly journals Septal Modulation of Excitatory Transmission in Hippocampus

2003 ◽  
Vol 90 (4) ◽  
pp. 2358-2366 ◽  
Author(s):  
Laura Lee Colgin ◽  
Enikö A. Kramár ◽  
Christine M. Gall ◽  
Gary Lynch
Keyword(s):  
Granule Cells ◽  
Cannabinoid Receptor ◽  
Mossy Fiber ◽  
Acetylcholinesterase Inhibitor ◽  
Molecular Layer ◽  
Hippocampal Slices ◽  
Muscarinic Acetylcholine Receptor ◽  
Single Pulse ◽  
Perforant Path ◽  
Synaptic Responses

Application of the acetylcholinesterase inhibitor physostigmine to conventional hippocampal slices caused a significant reduction of field excitatory postsynaptic potentials (EPSPs) elicited by single pulse stimulation to the medial perforant path. Similar but smaller effects were obtained in the lateral perforant path and other excitatory pathways within hippocampus. The reductions were blocked by atropine, were not accompanied by evident changes in the EPSP waveform, and were eliminated by lesions to the cholinergic septo-hippocampal projections. Antidromic responses to mossy fiber stimulation, recorded in stratum granulosum, were not affected by the drug. However, paired-pulse facilitation was reliably increased, indicating that the depressed synaptic responses were secondary to reductions in transmitter release. The absence of cholinergic axo-axonic connections in the molecular layer suggests that physostigmine reduces presynaptic release by increasing retrograde signaling from the granule cells. In accord with this, an antagonist of the CB1 cannabinoid receptor eliminated the effects of physostigmine on synaptic responses, while an antagonist of the presynaptically located m2 muscarinic acetylcholine receptor did not. This is in contrast to previously reported effects involving application of cholinergic agonists, in which presynaptic inhibition likely results from direct activation of presynaptically located muscarinic receptors. In summary, it is proposed that the cholinergic inputs from the septum to the middle molecular layer modulate, via endocannabinoid release, the potency of the primary excitatory afferent of hippocampus.

Medial Perforant Path Inhibition Mediated by mGluR7 Is Reduced After Status Epilepticus

2004 ◽  
Vol 92 (3) ◽  
pp. 1549-1557 ◽  
Author(s):  
Kristopher J. Bough ◽  
David D. Mott ◽  
Raymond J. Dingledine
Keyword(s):  
Status Epilepticus ◽  
Latent Period ◽  
Adult Mouse ◽  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Perforant Path ◽  
Double Knockout ◽  
Metabotropic Glutamate ◽  
Selective Agonists ◽  
Genetically Manipulated

Metabotropic glutamate receptor (mGluR)-mediated inhibition within the dentate gyrus is altered after epilepsy. Whether these changes occur during the developmental period of the disease (i.e., the latent period) has not yet been investigated. Field excitatory postsynaptic potentials (fEPSPs) were recorded in the lateral (LPP) and medial perforant path (MPP) simultaneously in adult mouse hippocampal slices 3–9 days after pilocarpine (PILO)-induced status epilepticus. Genetically manipulated mice (mGluR8 knockout and mGluR4/8 double knockout) and pharmacologically selective agonists were used to identify specific mGluR subtypes affected after PILO. Pharmacological activation of mGluR7 by L-AP4 in both wild-type and mGluR4/8 double knockout mice selectively reduced fEPSPs in the MPP, but not LPP, and this level of inhibition was significantly reduced 3–9 days after PILO-induced SE. Activation of mGluR2/3 reversibly depressed the fEPSP slopes in both the MPP and LPP, but no alterations were noted after PILO. mGluR8 activation selectively inhibited evoked responses in the LPP, but not in the MPP, and this level of inhibition did not change after PILO treatment. These data suggest that reduced presynaptic inhibition mediated by mGluR7, but not mGluR2/3 or mGluR8, may play a role during the latent period in generating hyperexcitability in the dentate and thereby contribute to epileptogenesis.

Effects of aging on axon terminals in the dentate molecular layer

1987 ◽  
Vol 45 ◽  
pp. 928-929
Author(s):  
K. Cullen-Dockstader ◽  
E. Fifkova
Keyword(s):  
Granule Cells ◽  
Molecular Layer ◽  
Age Groups ◽  
Long Term Potentiation ◽  
Male Rats ◽  
Perforant Path ◽  
Axon Terminals ◽  
Fischer 344 ◽  
Spatial Memory Deficit ◽  
Effects Of Aging

Normal aging results in a pronounced spatial memory deficit associated with a rapid decay of long-term potentiation at the synapses between the perforant path and spines in the medial and distal thirds of the dentate molecular layer (DML), suggesting the alteration of synaptic transmission in the dentate fascia. While the number of dentate granule cells remains unchanged, and there are no obvious pathological changes in these cells associated with increasing age, the density of their axospinous contacts has been shown to decrease. There are indications that the presynaptic element is affected by senescence before the postsynaptic element, yet little attention has been given to the fine structure of the remaining axon terminals. Therefore, we studied the axon terminals of the perforant path in the DML across three age groups.5 Male rats (Fischer 344) of each age group (3, 24 and 30 months), were perfused through the aorta.

Long-term depression of naive synapses in adult hippocampus induced by asynchronous synaptic activity

1995 ◽  
Vol 73 (6) ◽  
pp. 2596-2601 ◽  
Author(s):  
S. Otani ◽  
J. A. Connor
Keyword(s):  
Receptor Antagonist ◽  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Synaptic Activity ◽  
Synthesis Inhibitor ◽  
Long Term Depression ◽  
Metabotropic Glutamate ◽  
Adult Rat ◽  
Adult Hippocampus

1. Two independent Schaffer collateral pathways converging to the same pyramidal cell were alternately stimulated by 2-Hz trains (900 pulses) offset by a 150-ms interval in adult rat hippocampal slices. The second input underwent an immediate and persistent long-term depression (LTD). Depression in the first input was smaller than the second input. A narrower interpulse interval (20 ms) failed to induce LTD in either input. 2. Neither the N-methyl-D-aspartate receptor antagonist DL-2-amino-5-phosphonovaleric acid nor the metabotropic glutamate receptor antagonist (+)-alpha-methyl-4-carboxylphenyl-glycine blocked this associative LTD. However, coapplication of these two antagonists blocked LTD. 3. Associative LTD was blocked by prior injection of the Ca2+ chelator bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid into the postsynaptic cell and by bath-applied L-NG-nitroarginine, a nitric oxide synthesis inhibitor. 4. We propose that temporally confined, asynchronous synaptic activity weakens the efficacy of naive synapses in slices from the adult hippocampus.

Requirement of Protein Synthesis for Group I mGluR-Mediated Induction of Epileptiform Discharges

1998 ◽  
Vol 80 (2) ◽  
pp. 989-993 ◽  
Author(s):  
Lisa R. Merlin ◽  
Peter J. Bergold ◽  
Robert K. S. Wong
Keyword(s):  
Protein Synthesis ◽  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Progressive Increase ◽  
Protein Synthesis Inhibitors ◽  
Burst Frequency ◽  
Metabotropic Glutamate ◽  
Epileptiform Discharges ◽  
Group I

Merlin, Lisa R., Peter J. Bergold, and Robert K. S. Wong. Requirement of protein synthesis for group I mGluR-mediated induction of epileptiform discharges. J. Neurophysiol. 80: 989–993, 1998. Picrotoxin (50 μM) elicited rhythmic synchronized bursting in CA3 pyramidal cells in guinea pig hippocampal slices. Addition of the selective group I metabotropic glutamate receptor (mGluR) agonist ( S)-3,5-dihydroxyphenylglycine (25 μM) elicited an increase in burst frequency. This was soon followed by a slowly progressive increase in burst duration (BD), converting the brief 250–520 ms picrotoxin-induced synchronized bursts into prolonged discharges of 1–5 s in duration. BD was significantly increased within 60 min and reached a maximum after 2–2.5 h of agonist exposure. The protein synthesis inhibitors anisomycin (15 μM) or cycloheximide (25 μM) significantly impeded the mGluR-mediated development of the prolonged bursts; 90–120 min of agonist application failed to elicit the expected burst prolongation. By contrast, the mGluR-mediated enhancement of burst frequency progressed unimpeded. Furthermore, protein synthesis inhibitors had no significant effect on the frequency or duration of fully developed mGluR-induced prolonged discharges. These results suggest that the group I mGluR-mediated prolongation of synchronized bursts has a protein synthesis-dependent mechanism.

scholarly journals Differential ability of the dorsal and ventral rat hippocampus to exhibit group I metabotropic glutamate receptor–dependent synaptic and intrinsic plasticity

2017 ◽  
Vol 1 ◽  
pp. 239821281668979 ◽  
Author(s):  
Patrick Tidball ◽  
Hannah V. Burn ◽  
Kai Lun Teh ◽  
Arturas Volianskis ◽  
Graham L. Collingridge ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Longitudinal Axis ◽  
Functional Differentiation ◽  
Rat Hippocampus ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Intrinsic Plasticity

Background: The hippocampus is critically involved in learning and memory processes. Although once considered a relatively homogenous structure, it is now clear that the hippocampus can be divided along its longitudinal axis into functionally distinct domains, responsible for the encoding of different types of memory or behaviour. Although differences in extrinsic connectivity are likely to contribute to this functional differentiation, emerging evidence now suggests that cellular and molecular differences at the level of local hippocampal circuits may also play a role. Methods: In this study, we have used extracellular field potential recordings to compare basal input/output function and group I metabotropic glutamate receptor-dependent forms of synaptic and intrinsic plasticity in area CA1 of slices taken from the dorsal and ventral sectors of the adult rat hippocampus. Results: Using two extracellular electrodes to simultaneously record field EPSPs and population spikes, we show that dorsal and ventral hippocampal slices differ in their basal levels of excitatory synaptic transmission, paired-pulse facilitation, and EPSP-to-Spike coupling. Furthermore, we show that slices taken from the ventral hippocampus have a greater ability than their dorsal counterparts to exhibit long-term depression of synaptic transmission and EPSP-to-Spike potentiation induced by transient application of the group I mGluR agonist ( RS)-3,5-dihydroxyphenylglycine. Conclusions: Together, our results provide further evidence that the information processing properties of local hippocampal circuits differ in the dorsal and ventral hippocampal sectors, and that these differences may in turn contribute to the functional differentiation that exists along the hippocampal longitudinal axis.

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