scholarly journals Postsynaptic Signals Mediating Induction of Long-Term Synaptic Depression in the Entorhinal Cortex

2008 ◽  
Vol 2008 ◽  
pp. 1-9 ◽  
Author(s):  
Saïd Kourrich ◽  
Stephen D. Glasgow ◽  
Douglas A. Caruana ◽  
C. Andrew Chapman

The entorhinal cortex receives a large projection from the piriform cortex, and synaptic plasticity in this pathway may affect olfactory processing. In vitro whole cell recordings have been used here to investigate postsynaptic signalling mechanisms that mediate the induction of long-term synaptic depression (LTD) in layer II entorhinal cortex cells. To induce LTD, pairs of pulses, using a 30-millisecond interval, were delivered at 1 Hz for 15 minutes. Induction of LTD was blocked by the NMDA receptor antagonist APV and by the calcium chelator BAPTA, consistent with a requirement for calcium influx via NMDA receptors. Induction of LTD was blocked when the FK506 was included in the intracellular solution to block the phosphatase calcineurin. Okadaic acid, which blocks activation of protein phosphatases 1 and 2a, also prevented LTD. Activation of protein phosphatases following calcium influx therefore contributes to induction of LTD in layer II of the entorhinal cortex.

2003 ◽  
Vol 89 (4) ◽  
pp. 2112-2119 ◽  
Author(s):  
Saı̈d Kourrich ◽  
C. Andrew Chapman

The entorhinal cortex receives a large projection from the piriform (primary olfactory) cortex and, in turn, provides the hippocampal formation with most of its cortical sensory input. Synaptic plasticity in this pathway may therefore affect the processing of olfactory information and memory encoding. We have recently found that long-term synaptic depression (LTD) can be induced in this pathway in vivo by repetitive paired-pulse stimulation but not by low-frequency (1 Hz) stimulation with single pulses. Here, we have used field potential recordings to investigate the stimulation parameters and transmitter receptors required for the induction of LTD in the rat entorhinal cortex in vitro. The effectiveness of low-frequency stimulation (900 pulses at 1 or 5 Hz) and repeated delivery of pairs of stimulation pulses (30-ms interpulse interval) was assessed. Only repeated paired-pulse stimulation resulted in lasting LTD, and a low-intensity paired-pulse stimulation protocol that induces LTD in vivo was only effective in the presence of the GABAA receptor antagonist bicuculline (50 μM). LTD could also be induced in normal ACSF, however, by increasing the number of pulse-pairs delivered and by increasing the stimulation intensity during LTD induction. The induction of LTD was blocked by constant bath application of the N-methyl-d-aspartate (NMDA) glutamate receptor antagonist d-2-amino-5-phosphonovalerate (50 μM), indicating that LTD is dependent on NMDA receptor activation. However, LTD was not blocked by the group I/II mGluR antagonist (RS)-α-ethyl-4-carboxyphenylglycine (500 μM) or by bicuculline (50 μM). The induction of LTD in the entorhinal cortex in vitro is therefore dependent on intense stimulation that recruits activation of NMDA receptors, but does not require concurrent activation of mGluRs or inhibitory synaptic inputs.


1993 ◽  
Vol 69 (3) ◽  
pp. 1000-1004 ◽  
Author(s):  
Y. B. Liu ◽  
J. F. Disterhoft ◽  
N. T. Slater

1. The long-term enhancement of synaptic excitability in CA1 hippocampal pyramidal neurons produced by activation of metabotropic glutamate receptors (mGluRs) was studied in rabbit hippocampal slices in vitro. 2. Bath application of the mGluR agonist (1S,3R)-1-aminocyclopentane-1,3- dicarboxylic acid (1S,3R-ACPD) (5-20 microM) for 20 min produced a reversible depolarization of membrane potentiatil, blockade of spike accommodation, and increase in input resistance of CA1 neurons. However, a long-lasting increase in synaptic excitability was observed: single stimuli applied to the Schaffer collateral commisural fiber pathway evoked epileptiform discharges in the presence of 1S,3R-ACPD and after the washout of 1S,3R-ACPD, persistent paroxysmal depolarization shifts (PDSs) were evoked by afferent stimulation. A long-lasting enhancement of synaptic excitability was also observed in the presence of the NMDA receptor antagonist D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5), which blocked the stimulation-evoked PDS and associated afterdischarges. 3. When biphasic, monosynaptically evoked inhibitory post-synaptic potentials (IPSPs) were recorded in the presence of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10–15 microM) and D-AP5 (20 microM), the bath application of 1S,3R-ACPD produced a significant reduction (approximately 50%) of both components of the IPSP, which persisted after the washout of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)


1999 ◽  
Vol 81 (3) ◽  
pp. 1036-1044 ◽  
Author(s):  
Hannah Dvorak-Carbone ◽  
Erin M. Schuman

Long-term depression of temporoammonic-CA1 hippocampal synaptic transmission. The temporoammonic pathway, the direct projection from layer III of the entorhinal cortex to area CA1 of the hippocampus, includes both excitatory and inhibitory components that are positioned to be an important source of modulation of the hippocampal output. However, little is known about synaptic plasticity in this pathway. We used field recordings in hippocampal slices prepared from mature (6- to 8-wk old) rats to study long-term depression (LTD) in the temporoammonic pathway. Low-frequency (1 Hz) stimulation (LFS) for 10 min resulted in a depression of the field response that lasted for ≥1 h. This depression was saturable by multiple applications of LFS. LTD induction was unaffected by the blockade of either fast (GABAA) or slow (GABAB) inhibition. Temporoammonic LTD was inhibited by the presence of the N-methyl-d-aspartate (NMDA) receptor antagonist AP5, suggesting a dependence on calcium influx. Full recovery from depression could be induced by high-frequency (100 Hz) stimulation (HFS); in the presence of the GABAA antagonist bicuculline, HFS induced recovery above the original baseline level. Similarly, HFS or θ-burst stimulation (TBS) applied to naive slices caused little potentiation, whereas HFS or TBS applied in the presence of bicuculline resulted in significant potentiation of the temporoammonic response. Our results show that, unlike the Schaffer collateral input to CA1, the temporoammonic input in mature animals is easy to depress but difficult to potentiate.


1988 ◽  
Vol 59 (5) ◽  
pp. 1476-1496 ◽  
Author(s):  
R. S. Jones ◽  
U. Heinemann

1. Extracellular recordings were made from slices of hippocampus plus parahippocampal regions maintained in vitro. Field potentials, recorded in the entorhinal cortex after stimulation in the subiculum, resembled those observed in vivo. 2. Washout of magnesium from the slices resulted in paroxysmal events which resembled those occurring during sustained seizures in vivo. These events were greatest in amplitude and duration in layers IV/V of the medial entorhinal cortex and could occur both spontaneously and in response to subicular stimulation. Spontaneous seizure-like events were not prevented by severing the connections between the hippocampus and entorhinal cortex, but much smaller and shorter events occurring in the dentate gyrus were stopped by this manipulation. Both spontaneous and evoked paroxysmal events were blocked by perfusion with the N-methyl-D-aspartate (NMDA) receptor antagonist, DL-2-amino-5-phosphonovalerate (2-AP5). 3. Neurons in layers IV/V were characterized by intracellular recording. Injection of depolarizing current in most cells evoked a train of nondecrementing action potentials with only weak spike frequency accommodation and little or no posttrain after hyperpolarization. 4. A small number of cells displayed burst response when depolarized by positive current. The burst consisted of a slow depolarization with superimposed action potentials which decreased in amplitude and increased in duration during the discharge. The burst was terminated by a strong after hyperpolarization and thereafter, during prolonged current pulses a train of nondecrementing spikes occurred. The burst response remained if the cell was held at hyperpolarized levels but was inactivated by holding the cell at a depolarized level. 5. Depolarizing synaptic potentials could be evoked by stimulation in the subiculum. A delayed and prolonged depolarization clearly decremented with membrane hyperpolarization and, occasionally, increased with depolarization. 6. Washout of magnesium from the slices resulted in an enhancement of the late depolarization and a reversal of its voltage dependence. Eventually a single shock to the subiculum evoked a large all-or-none paroxysmal depolarization associated with a massive increase in membrane conductance. Similar events occurred spontaneously in all cells tested. The paroxysmal depolarizations, both spontaneous and evoked, were rapidly blocked by 2-AP5. 7. It is concluded that medial entorhinal cortical cells possess several intrinsic and synaptic properties which confer an extreme susceptibility to generation of sustained seizure activity.(ABSTRACT TRUNCATED AT 400 WORDS)


Animals ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2570
Author(s):  
Heiko Henning ◽  
Anne-Marie Luther ◽  
Dagmar Waberski

Retained cytoplasmic droplets (CD) are the most frequent sperm abnormality in boar semen. A high incidence of CD is associated with subfertility, but the underlaying reasons are not well understood. The storage of extended semen might augment the adverse effects of CD on essential steps towards fertilization, such as capacitation. The aim of this study was to examine whether the enhanced presence of CD in boar semen influences sperm’s response to the capacitation stimulus bicarbonate during long-term semen storage. Extended semen samples (n = 78) from 13 artificial insemination centers were analyzed using a flow cytometric calcium influx assay. Samples with >15% of CD showed a reduced specific response to bicarbonate and a higher non-specific destabilization after storage for 96 h and subsequent incubation at 38 °C in three variants of Tyrode`s medium (p < 0.05). The size of the bicarbonate-responsive sperm population was inversely correlated with the presence of CD-bearing sperm (r = −0.61, p < 0.01). Samples with ≤15% and samples with >15% of CD did not differ in motility or viability and acrosome integrity during semen storage. In conclusion, incomplete epididymal sperm maturation impairs the in vitro capacitation ability and promotes sperm destabilization in stored boar semen.


1993 ◽  
Vol 69 (4) ◽  
pp. 1150-1159 ◽  
Author(s):  
A. Colino ◽  
R. C. Malenka

1. The mechanisms underlying the induction of long-term potentiation (LTP) in the medial and lateral perforant paths were studied by recording excitatory postsynaptic potentials (EPSPs) from rat dentate granule cells in vitro using extracellular and whole-cell recording techniques. 2. Paired stimuli (interstimulus interval, 50-1,000 ms) resulted in facilitation of the lateral and depression of the medial perforant path-evoked EPSPs, respectively. This physiological difference was used to isolate responses evoked by stimulation of a single path. 3. Tetanic stimulation induced LTP in both pathways, although the magnitude of LTP in the lateral perforant path was significantly less than that in the medial perforant path. Both forms of LTP were blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovaleric acid (D-APV). 4. Buffering intracellular calcium by loading granule cells with the calcium chelator bis (O-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid prevented LTP in both pathways. 5. Pairing of low-frequency (0.25 Hz) afferent stimulation with postsynaptic depolarization induced LTP in the medial but not the lateral perforant path. However, pairing of higher-frequency stimulation (1-4 Hz) with postsynaptic depolarization did potentiate the lateral perforant path-evoked EPSP in some cells. 6. Both the medial and lateral perforant path-evoked EPSPs had two components; a fast component blocked by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione and a slower, voltage-dependent component blocked by D-APV. 7. The results indicate that the induction of LTP in both the medial and lateral perforant paths requires activation of postsynaptic NMDA receptors and a rise in intracellular calcium.(ABSTRACT TRUNCATED AT 250 WORDS)


2006 ◽  
Vol 96 (6) ◽  
pp. 3006-3015 ◽  
Author(s):  
Douglas A. Caruana ◽  
Robert E. Sorge ◽  
Jane Stewart ◽  
C. Andrew Chapman

Dopaminergic modulation of neuronal function has been extensively studied in the prefrontal cortex, but much less is known about its effects on glutamate-mediated synaptic transmission in the entorhinal cortex. The mesocortical dopamine system innervates the superficial layers of the lateral entorhinal cortex and may therefore modulate sensory inputs to this area. In awake rats, systemic administration of the dopamine reuptake inhibitor GBR12909 (10 mg/kg, ip) enhanced extracellular dopamine levels in the entorhinal cortex and significantly facilitated field excitatory postsynaptic potentials (fEPSPs) in layer II evoked by piriform cortex stimulation. An analysis of the receptor subtypes involved in the facilitation of evoked fEPSPs was conducted using horizontal slices of lateral entorhinal cortex in vitro. The effects of 15-min bath application of dopamine on synaptic responses were bidirectional and concentration dependent. Synaptic responses were enhanced by 10 μM dopamine and suppressed by concentrations of 50 and 100 μM. The D1-receptor antagonist SCH23390 (50 μM) blocked the significant facilitation of synaptic responses induced by 10 μM dopamine and the D2-receptor antagonist sulpiride (50 μM) prevented the suppression of fEPSPs observed with higher concentrations of dopamine. We propose here that dopamine release in the lateral entorhinal cortex, acting through D1 receptors, can lead to an enhancement of the salience of sensory representations carried to this region from adjacent sensory cortices.


2016 ◽  
Vol 116 (2) ◽  
pp. 658-670 ◽  
Author(s):  
Daniel W. Sparks ◽  
C. Andrew Chapman

The superficial layers of the entorhinal cortex receive sensory and associational cortical inputs and provide the hippocampus with the majority of its cortical sensory input. The parasubiculum, which receives input from multiple hippocampal subfields, sends its single major output projection to layer II of the entorhinal cortex, suggesting that it may modulate processing of synaptic inputs to the entorhinal cortex. Indeed, stimulation of the parasubiculum can enhance entorhinal responses to synaptic input from the piriform cortex in vivo. Theta EEG activity contributes to spatial and mnemonic processes in this region, and the current study assessed how stimulation of the parasubiculum with either single pulses or short, five-pulse, theta-frequency trains may modulate synaptic responses in layer II entorhinal stellate neurons evoked by stimulation of layer I afferents in vitro. Parasubicular stimulation pulses or trains suppressed responses to layer I stimulation at intervals of 5 ms, and parasubicular stimulation trains facilitated layer I responses at a train-pulse interval of 25 ms. This suggests that firing of parasubicular neurons during theta activity may heterosynaptically enhance incoming sensory inputs to the entorhinal cortex. Bath application of the hyperpolarization-activated cation current (Ih) blocker ZD7288 enhanced the facilitation effect, suggesting that cholinergic inhibition of Ih may contribute. In addition, repetitive pairing of parasubicular trains and layer I stimulation induced a lasting depression of entorhinal responses to layer I stimulation. These findings provide evidence that theta activity in the parasubiculum may promote heterosynaptic modulation effects that may alter sensory processing in the entorhinal cortex.


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