P3-060: OLEUROPEIN REVERSED AGE-DEPENDENT IMPAIRMENT TO SUSTAIN LONG-TERM POTENTIATION (LTP) IN PERFORANT PATH-DENTATE GYRUS SYNAPSES AND INCREASED MICROTUBULE-ASSOCIATED PROTEIN 2 LEVEL

Abstract Neuroligin-3 (Nlgn3), a neuronal adhesion protein implicated in autism spectrum disorder (ASD), is expressed at excitatory and inhibitory postsynapses and hence may regulate neuronal excitation/inhibition balance. To test this hypothesis, we recorded field excitatory postsynaptic potentials (fEPSPs) in the dentate gyrus of Nlgn3 knockout (KO) and wild-type mice. Synaptic transmission evoked by perforant path stimulation was reduced in KO mice, but coupling of the fEPSP to the population spike was increased, suggesting a compensatory change in granule cell excitability. These findings closely resemble those in neuroligin-1 (Nlgn1) KO mice and could be partially explained by the reduction in Nlgn1 levels we observed in hippocampal synaptosomes from Nlgn3 KO mice. However, unlike Nlgn1, Nlgn3 is not necessary for long-term potentiation. We conclude that while Nlgn1 and Nlgn3 have distinct functions, both are required for intact synaptic transmission in the mouse dentate gyrus. Our results indicate that interactions between neuroligins may play an important role in regulating synaptic transmission and that ASD-related neuroligin mutations may also affect the synaptic availability of other neuroligins.

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Oleuropein Improves Long Term Potentiation at Perforant Path-dentate Gyrus Synapses in vivo

Chinese Herbal Medicines ◽

10.1016/s1674-6384(15)60047-8 ◽

2015 ◽

Vol 7 (3) ◽

pp. 255-260 ◽

Cited By ~ 3

Author(s):

Fei-fei Pu ◽

Song Yin ◽

Hong-ying Chen ◽

Zhi Dai ◽

Tian-xiu Qian ◽

...

Keyword(s):

Dentate Gyrus ◽

Long Term Potentiation ◽

Perforant Path ◽

Term Potentiation

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Long-term potentiation expands information content of hippocampal dentate gyrus synapses

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1716189115 ◽

2018 ◽

Vol 115 (10) ◽

pp. E2410-E2418 ◽

Cited By ~ 19

Author(s):

Cailey Bromer ◽

Thomas M. Bartol ◽

Jared B. Bowden ◽

Dusten D. Hubbard ◽

Dakota C. Hanka ◽

...

Keyword(s):

Synaptic Plasticity ◽

Dentate Gyrus ◽

Storage Capacity ◽

Unit Length ◽

Long Term Potentiation ◽

Information Storage ◽

Perforant Path ◽

Hippocampal Dentate Gyrus ◽

Term Potentiation

An approach combining signal detection theory and precise 3D reconstructions from serial section electron microscopy (3DEM) was used to investigate synaptic plasticity and information storage capacity at medial perforant path synapses in adult hippocampal dentate gyrus in vivo. Induction of long-term potentiation (LTP) markedly increased the frequencies of both small and large spines measured 30 minutes later. This bidirectional expansion resulted in heterosynaptic counterbalancing of total synaptic area per unit length of granule cell dendrite. Control hemispheres exhibited 6.5 distinct spine sizes for 2.7 bits of storage capacity while LTP resulted in 12.9 distinct spine sizes (3.7 bits). In contrast, control hippocampal CA1 synapses exhibited 4.7 bits with much greater synaptic precision than either control or potentiated dentate gyrus synapses. Thus, synaptic plasticity altered total capacity, yet hippocampal subregions differed dramatically in their synaptic information storage capacity, reflecting their diverse functions and activation histories.

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Long-Term Potentiation in the Dentate Gyrus Is Not Linked to Increased Extracellular Glutamate Concentration

Journal of Neurophysiology ◽

10.1152/jn.1999.81.4.1741 ◽

1999 ◽

Vol 81 (4) ◽

pp. 1741-1748 ◽

Cited By ~ 14

Author(s):

T. M. Jay ◽

E. Zilkha ◽

T. P. Obrenovitch

Keyword(s):

Dentate Gyrus ◽

Synaptic Cleft ◽

Long Term Potentiation ◽

Perforant Path ◽

Mammalian Brain ◽

Excitatory Postsynaptic Potential ◽

Extracellular Glutamate ◽

Glutamate Concentration ◽

Term Potentiation

Long-term potentiation in the dentate gyrus is not linked to increased extracellular glutamate concentration. Long-term potentiation (LTP) of excitatory transmission is a likely candidate for the encoding and storage of information in the mammalian brain. There is a general agreement that LTP involves an increase in synaptic strength, but the mechanisms underlying this persistent change are unclear and controversial. Synaptic efficacy may be enhanced because more transmitter glutamate is released or because postsynaptic responsiveness increases or both. The purpose of this study was to examine whether increased extracellular glutamate concentration was associated with the robust and well-characterized LTP that can be induced in the rat dentate gyrus. To favor the detection of any putative change in extracellular glutamate associated with LTP, our experimental strategy included the following features. 1) Two separate series of experiments were carried out with animals under pentobarbital or urethan anesthesia; 2) changes in extracellular concentration of glutamate were monitored continuously by microdialysis coupled to enzyme amperometry; and 3) dialysate glutamate levels and changes in the slope of excitatory postsynaptic potential evoked by activation of the perforant path were recorded precisely at the same site. Tetanic stimulation of the perforant path increased persistently test-evoked responses in the dentate gyrus (by 19 and 14% in barbiturate and urethan group, respectively), but there was no glutamate change either during or after LTP induction and no indication of increased glutamate efflux when low-frequency stimulation was applied. The results do not rule out a possible contribution of enhanced glutamate exocytosis to LTP induction and/or maintenance because such a presynaptic change may not be detectable extracellularly. However, our findings and other data supporting the notion that neurotransmitter glutamate may hardly leak out of the synaptic cleft conflict with the hypothesis that LTP could also involve a broad synaptic spillover of glutamate.

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Low-frequency stimulation of the perforant path produces long-term potentiation in the dentate gyrus of unanesthetized rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y83-172 ◽

1983 ◽

Vol 61 (10) ◽

pp. 1156-1161 ◽

Cited By ~ 13

Author(s):

R. W. Skelton ◽

J. J. Miller ◽

A. G. Phillips

Keyword(s):

Dentate Gyrus ◽

Low Frequency ◽

Long Term Potentiation ◽

Perforant Path ◽

High Frequency Stimulation ◽

Synaptic Efficacy ◽

Term Potentiation ◽

Frequency Stimulation ◽

Stimulation Of

Brief periods of high-frequency stimulation of hippocampal afferents produce long-term potentiation (LTP) of synaptic transmission, but the minimum frequency capable of inducing this alteration in synaptic efficacy has not been specified. The present study used the repeated measurement of input–output curves in the perforant path – dentate gyrus system of freely moving rats to monitor synaptic efficacy and found that stimulation at 0.2 Hz, but not 0.04 Hz produced LTP. These results suggest that the minimum stimulation frequency capable of producing LTP is lower than previously described. Possible reasons for the discrepancy between the present and previous findings are discussed, along with the implications of low-frequency potentiation.

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Somatostatin-positive interneurons in the dentate gyrus of mice provide local- and long-range septal synaptic inhibition

eLife ◽

10.7554/elife.21105 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 28

Author(s):

Mei Yuan ◽

Thomas Meyer ◽

Christoph Benkowitz ◽

Shakuntala Savanthrapadian ◽

Laura Ansel-Bollepalli ◽

...

Keyword(s):

Dentate Gyrus ◽

Spatial Information ◽

Molecular Layer ◽

Activity Patterns ◽

Long Term Potentiation ◽

Medial Septum ◽

Perforant Path ◽

Term Potentiation ◽

Memory Acquisition

Somatostatin-expressing-interneurons (SOMIs) in the dentate gyrus (DG) control formation of granule cell (GC) assemblies during memory acquisition. Hilar-perforant-path-associated interneurons (HIPP cells) have been considered to be synonymous for DG-SOMIs. Deviating from this assumption, we show two functionally contrasting DG-SOMI-types. The classical feedback-inhibitory HIPPs distribute axon fibers in the molecular layer. They are engaged by converging GC-inputs and provide dendritic inhibition to the DG circuitry. In contrast, SOMIs with axon in the hilus, termed hilar interneurons (HILs), provide perisomatic inhibition onto GABAergic cells in the DG and project to the medial septum. Repetitive activation of glutamatergic inputs onto HIPP cells induces long-lasting-depression (LTD) of synaptic transmission but long-term-potentiation (LTP) of synaptic signals in HIL cells. Thus, LTD in HIPPs may assist flow of spatial information from the entorhinal cortex to the DG, whereas LTP in HILs may facilitate the temporal coordination of GCs with activity patterns governed by the medial septum.

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