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

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.

2020 ◽  
Vol 27 (9) ◽  
pp. 380-389
Author(s):  
Christine J. Fontaine ◽  
Erin L. Gräfe ◽  
Cristina Pinar ◽  
Itziar Bonilla-Del Río ◽  
Pedro Grandes ◽  
...  

Cannabinoid receptors are widely expressed throughout the hippocampal formation, but are particularly dense in the dentate gyrus (DG) subregion. We, and others, have shown in mice that cannabinoid type 1 receptors (CB1Rs) are involved in a long-term depression (LTD) that can be induced by prolonged 10 Hz stimulation of the medial perforant path (MPP)-granule cell synaptic input to the DG. Here, we extend this work to examine the involvement of CB1Rs in other common forms of LTD in the hippocampus of juvenile male and female Sprague–Dawley rats (Rattus norvegicus). We found, as in mice, that prolonged 10 Hz stimulation (6000 pulses) could reliably induce a form of LTD that was dependent upon CB1R activation. In addition, we also discovered a role for both CB1R and mGluR proteins in LTD induced with 1 Hz low-frequency stimulation (1 Hz-LTD; 900 pulses) and in LTD induced by bath application of the group I mGluR agonist (RS)-3,5-Dihydroxyphenylglycine (DHPG; DHPG-LTD). This study elucidates an essential role for endocannabinoid receptors in a number of forms of LTD in the rat DG, and identifies a novel role for CB1Rs as potential therapeutic targets for conditions that involve impaired LTD in the DG.


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.


2014 ◽  
Vol 111 (5) ◽  
pp. 1046-1055 ◽  
Author(s):  
Costanza Burattini ◽  
Giulia Battistini ◽  
Francesco Tamagnini ◽  
Giorgio Aicardi

The nucleus accumbens (NAc), a major component of the mesolimbic system, is involved in the mediation of reinforcing and addictive properties of many dependence-producing drugs. Glutamatergic synapses within the NAc can express plasticity, including a form of endocannabinoid (eCB)-long-term depression (LTD). Recent evidences demonstrate cross talk between eCB signaling pathways and those of other receptor systems, including serotonin (5-HT); the extensive colocalization of CB1 and 5-HT receptors within the NAc suggests the potential for interplay between them. In the present study, we found that 20-min low-frequency (4 Hz) stimulation (LFS-4Hz) of glutamatergic afferences in rat brain slices induces a novel form of eCB-LTD in the NAc core, which requires 5-HT2 and CB1 receptor activation and L-type voltage-gated Ca2+ channel opening. Moreover, we found that exogenous 5-HT application (5 μM, 20 min) induces an analogous LTD (5-HT-LTD) at the same synapses, requiring the activation of the same receptors and the opening of the same Ca2+ channels; LFS-4Hz-LTD and 5-HT-LTD were mutually occlusive. Present results suggest that LFS-4Hz induces the release of 5-HT, which acts at 5-HT2 postsynaptic receptors, increasing Ca2+ influx through L-type voltage-gated channels and 2-arachidonoylglycerol production and release; the eCB travels retrogradely and binds to presynaptic CB1 receptors, causing a long-lasting decrease of glutamate release, resulting in LTD. These observations might be helpful to understand the neurophysiological mechanisms underlying drug addiction, major depression, and other psychiatric disorders characterized by dysfunction of 5-HT neurotransmission in the NAc.


1996 ◽  
Vol 75 (2) ◽  
pp. 877-884 ◽  
Author(s):  
P. T. Huerta ◽  
J. E. Lisman

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.


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)


Author(s):  
Michael Lawrence G. Castañares ◽  
Greg J. Stuart ◽  
Vincent R. Daria

AbstractDendritic spikes in layer 5 pyramidal neurons (L5PNs) play a major role in cortical computation. While dendritic spikes have been studied extensively in apical and basal dendrites of L5PNs, whether oblique dendrites, which ramify in the input layers of the cortex, also generate dendritic spikes is unknown. Here we report the existence of dendritic spikes in apical oblique dendrites of L5PNs. In silico investigations indicate that oblique branch spikes are triggered by brief, low-frequency action potential (AP) trains (~40 Hz) and are characterized by a fast sodium spike followed by activation of voltage-gated calcium channels. In vitro experiments confirmed the existence of oblique branch spikes in L5PNs during brief AP trains at frequencies of around 60 Hz. Oblique branch spikes offer new insights into branch-specific computation in L5PNs and may be critical for sensory processing in the input layers of the cortex.


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