Long-Term Depression of Temporoammonic-CA1 Hippocampal Synaptic Transmission

1999 ◽  
Vol 81 (3) ◽  
pp. 1036-1044 ◽  
Author(s):  
Hannah Dvorak-Carbone ◽  
Erin M. Schuman
Keyword(s):  
Synaptic Transmission ◽  
Calcium Influx ◽  
Hippocampal Slices ◽  
Low Frequency ◽  
Nmda Receptor Antagonist ◽  
Long Term Depression ◽  
Field Recordings ◽  
Old Rats ◽  
Inhibitory Components

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.

Low-frequency stimulation at the troughs of theta-oscillation induces long-term depression of previously potentiated CA1 synapses

1996 ◽  
Vol 75 (2) ◽  
pp. 877-884 ◽  
Author(s):  
P. T. Huerta ◽  
J. E. Lisman
Keyword(s):  
Hippocampal Slices ◽  
Field Potential ◽  
Low Frequency ◽  
Long Term Depression ◽  
Low Frequency Stimulation ◽  
Bath Application ◽  
Stable Conditions ◽  
Theta Frequency ◽  
Frequency Stimulation

1. The induction of long-term weakening of synaptic transmission in rat hippocampal slices was examined in CA1 synapses during cholinergic modulation. 2. Bath application of the cholinergic agonist carbachol (50 microM) activated an oscillation of the local field potential in the theta-frequency range (5-12 Hz), termed theta. It was previously shown that a stimulation train of 40 single shocks (at 0.1 Hz) to the Schaffer collateral-commisural afferents, each synchronized with positive peaks of theta, caused homosynaptic long-term enhancement in CA1. Furthermore, long-term depression (LTD) was sporadically observed when the stimulation train was given at negative troughs of theta. Here we have sought to determine stable conditions for LTD induction during theta. 3. Synaptic weakening was reliably obtained, by giving 40 shocks (at 0.1 Hz) at theta-troughs, only in pathways that had been previously potentiated. This decrement, termed theta-LTD, was synapse specific because it did not occur in an independent pathway not stimulated during theta. The interval between the initial potentiating tetanus and theta-LTD induction could be as long as 90 min. 4. theta-LTD could be saturated; after consecutive episodes of theta-LTD induction, no significant further depression was obtained. Moreover, theta-LTD could be reversed by tetanic stimulation. 5. theta-LTD could prevent the induction of LTD by 600-900 pulses at 1 Hz. This suggests that the two protocols may share common mechanisms at the synaptic level. 6. We conclude that single presynaptic spikes that occur at low frequency and are properly timed to the troughs of theta may be a relevant mechanism for decreasing the strength of potentiated synapses.

Novel Form of Long-Term Synaptic Depression in Rat Hippocampus Induced By Activation of α1 Adrenergic Receptors

2004 ◽  
Vol 91 (2) ◽  
pp. 1071-1077 ◽  
Author(s):  
Cary L. Scheiderer ◽  
Lynn E. Dobrunz ◽  
Lori L. McMahon
Keyword(s):  
Synaptic Transmission ◽  
Receptor Antagonist ◽  
Adrenergic Receptors ◽  
Hippocampal Slices ◽  
Low Frequency ◽  
Adrenergic System ◽  
Normal Cognitive Function ◽  
Dependent Learning

Neurons located in the locus coeruleus project to hippocampus and provide noradrenergic innervation necessary for hippocampal-dependent learning and memory. The mechanisms underlying the function of norepinephrine (NE) in memory processing are unknown but likely reside in the ability of NE to modulate the efficacy of glutamate synaptic transmission via activation of G-protein-coupled adrenergic receptors. Here we show that application of NE to rat hippocampal slices in vitro induces a long-term depression (LTD) of synaptic transmission at excitatory CA3–CA1 synapses that persists for ≥40 min after agonist washout. This LTD, which we refer to as NE LTD, is mediated by activation of α1 adrenergic receptors because the α1 agonist methoxamine can induce LTD at the same magnitude as that induced with the nonselective adrenergic agonist NE. Furthermore, NE LTD induced by either NE or methoxamine is blocked with the α1 receptor antagonist, prazosin, but is unaffected by antagonists of α2 and β receptors. This plasticity persists in the presence of the GABAA receptor antagonist bicuculline, indicating that adrenergic modulation of GABAA receptor-mediated transmission does not underlie NE LTD. Induction of NE LTD requires presynaptic activity during agonist application and postsynaptic activation of N-methyl-d-aspartate receptors, fulfilling Hebbian criteria of coincident pre- and postsynaptic activity. The expression of NE LTD is likely to be postsynaptic because paired-pulse facilitation ratios during NE LTD expression are not different from baseline, similar to LTD induced by low-frequency stimulation. Thus we report the identification and characterization of a novel Hebbian form of LTD in hippocampus that is induced after activation of α1 adrenergic receptors. This plasticity may be a mechanism by which the adrenergic system participates in normal cognitive function.

The postsynaptic induction of nonassociative long-term depression of excitatory synaptic transmission in rat hippocampal slices

1993 ◽  
Vol 69 (1) ◽  
pp. 219-229 ◽  
Author(s):  
G. Christofi ◽  
A. V. Nowicky ◽  
S. R. Bolsover ◽  
L. J. Bindman
Keyword(s):  
Synaptic Transmission ◽  
Hippocampal Slices ◽  
Receptor Subtypes ◽  
Postsynaptic Neuron ◽  
Conditioning Procedure ◽  
Long Term Depression ◽  
Postsynaptic Potentials ◽  
The Mean ◽  
Conditioning Stimuli

1. Long-term depression (LTD) is an activity-dependent reduction in the strength of synaptic transmission that can persist for hours. It is a neural model for processes underlying learning and memory, such as extinction and forgetting. LTD of excitatory postsynaptic potentials (EPSPs) in cells of the CA1 region of hippocampal slices can be induced in an anti-Hebbian paradigm, i.e., by conditioning stimuli that activate the postsynaptic neuron in the absence of evoked synaptic transmission in the test pathway. Past work showed that LTD was not produced consistently in a pharmacologically untreated slice, but it could be induced more reliably when the conditioning stimuli were applied during block of evoked transmitter release. We have now defined further the conditions in which LTD can be obtained using postsynaptic conditioning by investigating 1) whether intracellular conditioning is effective, 2) the requirement for extracellular Ca2+, and 3) the consequences of selective block of glutamate ionotropic receptor subtypes during the conditioning procedure. 2. Intracellular recordings were made from CA1 pyramidal neurons. Test shocks were applied to the stratum radiatum except during conditioning, and the depolarizing slopes and amplitudes of evoked EPSPs were measured. The conditioning procedure activated the postsynaptic neuron either antidromically (via trains of shocks at 100 Hz applied to the axons in the alveus) or intracellularly (via depolarizing pulses of 1.5–3.5 nA). During conditioning, postsynaptic potentials (PSPs) evoked by the conditioning stimuli either were transiently blocked by bathing slices for 5 min in artificial cerebrospinal fluid (CSF) containing a high [Mg2+] or were reduced by glutamate antagonists. 3. When slices were bathed in CSF containing 25 mM Mg2+ and 2 mM Ca2+, evoked PSPs were transiently abolished; conditioning, either by antidromic or intracellular stimulation, always evoked a significant LTD. During the LTD produced by antidromic stimulation, the mean EPSP slope was 52.6 +/- 11.4% (mean +/- SE) of its control at 30–35 min after conditioning (n = 7). The LTD produced by intracellular conditioning was of similar magnitude: the mean EPSP slope was 57.2 +/- 11.6% of its control at 30-35 min postconditioning (n = 7). When slices were bathed in CSF containing 25 mM Mg2+ and 2 mM Ca2+ without conditioning stimuli, there was no LTD (mean EPSP slope 109 +/- 8.1% of its control at 30–35 min after reperfusion with CSF; n = 5).(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Aberrant activity of mitochondrial NCLX is linked to impaired synaptic transmission and is associated with mental retardation

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Alexandra Stavsky ◽  
Ohad Stoler ◽  
Marko Kostic ◽  
Tomer Katoshevsky ◽  
Essam A. Assali ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Synaptic Transmission ◽  
Calcium Influx ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Synaptic Activity ◽  
Calcium Transients ◽  
Lower Probability ◽  
Mitochondrial Calcium

AbstractCalcium dynamics control synaptic transmission. Calcium triggers synaptic vesicle fusion, determines release probability, modulates vesicle recycling, participates in long-term plasticity and regulates cellular metabolism. Mitochondria, the main source of cellular energy, serve as calcium signaling hubs. Mitochondrial calcium transients are primarily determined by the balance between calcium influx, mediated by the mitochondrial calcium uniporter (MCU), and calcium efflux through the sodium/lithium/calcium exchanger (NCLX). We identified a human recessive missense SLC8B1 variant that impairs NCLX activity and is associated with severe mental retardation. On this basis, we examined the effect of deleting NCLX in mice on mitochondrial and synaptic calcium homeostasis, synaptic activity, and plasticity. Neuronal mitochondria exhibited basal calcium overload, membrane depolarization, and a reduction in the amplitude and rate of calcium influx and efflux. We observed smaller cytoplasmic calcium transients in the presynaptic terminals of NCLX-KO neurons, leading to a lower probability of release and weaker transmission. In agreement, synaptic facilitation in NCLX-KO hippocampal slices was enhanced. Importantly, deletion of NCLX abolished long term potentiation of Schaffer collateral synapses. Our results show that NCLX controls presynaptic calcium transients that are crucial for defining synaptic strength as well as short- and long-term plasticity, key elements of learning and memory processes.

Contribution of Voltage-Gated Ca2+ Channels to Homosynaptic Long-Term Depression in the CA1 Region In Vitro

1997 ◽  
Vol 77 (3) ◽  
pp. 1651-1655 ◽  
Author(s):  
Brian R. Christie ◽  
Lalania K. Schexnayder ◽  
Daniel Johnston
Keyword(s):  
Hippocampal Formation ◽  
Low Frequency ◽  
Nmda Receptor Antagonist ◽  
Stratum Radiatum ◽  
Sprague Dawley ◽  
Long Term Depression ◽  
Voltage Gated ◽  
Ca1 Region

Christie, Brian R., Lalania K. Schexnayder, and Daniel Johnston. Contribution of voltage-gated Ca2+ channels to homosynaptic long-term depression in the CA1 region in vitro. J. Neurophysiol. 77: 1651–1655, 1997. Homosynaptic long-term depression (LTD) of synaptic efficacy was induced in field excitatory postsynaptic potentials by administration of 900 pulses at either 1 or 3 Hz in 2- to 3-wk-old Sprague-Dawley rats. The stimulation was administered via a bipolar stimulating electrode placed immediately adjacent to the recording electrode in the stratum radiatum region of the hippocampal CA1 subfield. Equivalent LTD induction occurred whether the slices were maintained at room temperature or at 32°C. Lowering bath Ca2+ to 0 mM, or increasing it to 4 mM, prevented the induction of the depression. The NMDA receptor antagonist d,l-2-amino-5-phosphonovaleric acid (50 μM) reversibly blocked the induction of homosynaptic LTD. In addition, the L-type voltage-gated calcium channel (VGCC) antagonist nimodipine (10 μM) and the R- and T-type VGCC antagonist NiCl2 (25 μM) also prevented homosynaptic LTD induction. These results indicate that in addition to N-methyl-d-aspartate receptor activity, Ca2+ influx via VGCCs can play an important role in the induction and expression of LTD induced by low-frequency stimulation in the hippocampal formation.

scholarly journals Activity-Dependent Plasticity of Astroglial Potassium and Glutamate Clearance

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Giselle Cheung ◽  
Jérémie Sibille ◽  
Jonathan Zapata ◽  
Nathalie Rouach
Keyword(s):  
Synaptic Transmission ◽  
Neuronal Activity ◽  
Hippocampal Slices ◽  
Low Frequency ◽  
Extracellular Potassium ◽  
Inward Currents ◽  
Frequency Stimulation ◽  
Short And Long Term ◽  
Acute Hippocampal Slices

Recent evidence has shown that astrocytes play essential roles in synaptic transmission and plasticity. Nevertheless, how neuronal activity alters astroglial functional properties and whether such properties also display specific forms of plasticity still remain elusive. Here, we review research findings supporting this aspect of astrocytes, focusing on their roles in the clearance of extracellular potassium and glutamate, two neuroactive substances promptly released during excitatory synaptic transmission. Their subsequent removal, which is primarily carried out by glial potassium channels and glutamate transporters, is essential for proper functioning of the brain. Similar to neurons, different forms of short- and long-term plasticity in astroglial uptake have been reported. In addition, we also present novel findings showing robust potentiation of astrocytic inward currents in response to repetitive stimulations at mild frequencies, as low as 0.75 Hz, in acute hippocampal slices. Interestingly, neurotransmission was hardly affected at this frequency range, suggesting that astrocytes may be more sensitive to low frequency stimulation and may exhibit stronger plasticity than neurons to prevent hyperexcitability. Taken together, these important findings strongly indicate that astrocytes display both short- and long-term plasticity in their clearance of excess neuroactive substances from the extracellular space, thereby regulating neuronal activity and brain homeostasis.

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