scholarly journals Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
David Vandael ◽  
Yuji Okamoto ◽  
Peter Jonas
Keyword(s):  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Brain Slices ◽  
High Frequency Stimulation ◽  
Short Term Plasticity ◽  
Glutamate Signaling ◽  
Frequency Stimulation ◽  
Post Tetanic Potentiation ◽  
Mossy Fiber Synapse ◽  
Ca3 Neurons

AbstractThe hippocampal mossy fiber synapse is a key synapse of the trisynaptic circuit. Post-tetanic potentiation (PTP) is the most powerful form of plasticity at this synaptic connection. It is widely believed that mossy fiber PTP is an entirely presynaptic phenomenon, implying that PTP induction is input-specific, and requires neither activity of multiple inputs nor stimulation of postsynaptic neurons. To directly test cooperativity and associativity, we made paired recordings between single mossy fiber terminals and postsynaptic CA3 pyramidal neurons in rat brain slices. By stimulating non-overlapping mossy fiber inputs converging onto single CA3 neurons, we confirm that PTP is input-specific and non-cooperative. Unexpectedly, mossy fiber PTP exhibits anti-associative induction properties. EPSCs show only minimal PTP after combined pre- and postsynaptic high-frequency stimulation with intact postsynaptic Ca2+ signaling, but marked PTP in the absence of postsynaptic spiking and after suppression of postsynaptic Ca2+ signaling (10 mM EGTA). PTP is largely recovered by inhibitors of voltage-gated R- and L-type Ca2+ channels, group II mGluRs, and vacuolar-type H+-ATPase, suggesting the involvement of retrograde vesicular glutamate signaling. Transsynaptic regulation of PTP extends the repertoire of synaptic computations, implementing a brake on mossy fiber detonation and a “smart teacher” function of hippocampal mossy fiber synapses.

scholarly journals Transsynaptic modulation of presynaptic short-term plasticity induction in hippocampal mossy fiber synapses

2020 ◽  
Author(s):  
David Vandael ◽  
Yuji Okamoto ◽  
Peter Jonas
Keyword(s):  
Pyramidal Neurons ◽  
Metabotropic Glutamate Receptor ◽  
Mossy Fiber ◽  
Brain Slices ◽  
High Frequency Stimulation ◽  
Glutamate Signaling ◽  
Metabotropic Glutamate ◽  
Frequency Stimulation ◽  
Ca3 Neurons ◽  
Type V

SUMMARYThe hippocampal mossy fiber synapse is a key synapse of the trisynaptic circuit of the hippocampus. Post-tetanic potentiation (PTP) is the most powerful form of plasticity at this synaptic connection. It is widely believed that mossy fiber PTP is an entirely presynaptic phenomenon, implying that PTP induction is input-specific, and requires neither activity of multiple inputs nor stimulation of postsynaptic neurons for induction. Thus, mossy fiber PTP appears to lack cooperativity and associativity that characterize other forms of plasticity. To directly test these predictions, we made paired recordings between single mossy fiber terminals and postsynaptic CA3 pyramidal neurons in rat brain slices. By stimulating parallel but non-overlapping mossy fiber bouton (MFB) inputs converging onto single CA3 neurons, we confirmed that PTP was inputspecific and non-cooperative. Unexpectedly, mossy fiber PTP showed anti-associative induction properties. Mossy fiber excitatory postsynaptic currents (EPSCs) showed only minimal PTP after combined pre- and postsynaptic high-frequency stimulation (HFS) with intact postsynaptic Ca2+ signaling (0.1 mM EGTA), but marked PTP in the absence of postsynaptic spiking and after suppression of postsynaptic Ca2+ signaling (10 mM EGTA). PTP was rescued by blocking Ca2+ entry via voltage-gated R-type and to a smaller extent L-type Ca2+channels. PTP was also recovered by extracellular application of group II metabotropic glutamate receptor (mGluR) antagonists and vacuolar-type (v-type) H+-ATPase inhibitors, suggesting the involvement of retrograde vesicular glutamate signaling. Transsynaptic regulation of PTP induction may increase the computational power of mossy fiber synapses, and implement a break on hippocampal mossy fiber detonation.

scholarly journals Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Nicholas P Vyleta ◽  
Carolina Borges-Merjane ◽  
Peter Jonas
Keyword(s):  
Granule Cells ◽  
Mossy Fiber ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Short Term ◽  
Short Term Plasticity ◽  
Cell Network ◽  
Post Tetanic Potentiation ◽  
Ca3 Pyramidal Cells ◽  
Ca3 Neurons

Mossy fiber synapses on CA3 pyramidal cells are 'conditional detonators' that reliably discharge postsynaptic targets. The 'conditional' nature implies that burst activity in dentate gyrus granule cells is required for detonation. Whether single unitary excitatory postsynaptic potentials (EPSPs) trigger spikes in CA3 neurons remains unknown. Mossy fiber synapses exhibit both pronounced short-term facilitation and uniquely large post-tetanic potentiation (PTP). We tested whether PTP could convert mossy fiber synapses from subdetonator into detonator mode, using a recently developed method to selectively and noninvasively stimulate individual presynaptic terminals in rat brain slices. Unitary EPSPs failed to initiate a spike in CA3 neurons under control conditions, but reliably discharged them after induction of presynaptic short-term plasticity. Remarkably, PTP switched mossy fiber synapses into full detonators for tens of seconds. Plasticity-dependent detonation may be critical for efficient coding, storage, and recall of information in the granule cell–CA3 cell network.

scholarly journals L-Type Calcium Channels Are Required for One Form of Hippocampal Mossy Fiber LTP

1998 ◽  
Vol 79 (4) ◽  
pp. 2181-2190 ◽  
Author(s):  
Ajay Kapur ◽  
Mark F. Yeckel ◽  
Richard Gray ◽  
Daniel Johnston
Keyword(s):  
Calcium Channels ◽  
High Frequency ◽  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Calcium Influx ◽  
Calcium Transients ◽  
High Frequency Stimulation ◽  
Frequency Stimulation ◽  
Ca3 Pyramidal Neurons ◽  
Postsynaptic Calcium

Kapur, Ajay, Mark F. Yeckel, Richard Gray, and Daniel Johnston. L-type calcium channels are required for one form of hippocampal mossy fiber LTP. J. Neurophysiol. 79: 2181–2190, 1998. The requirement of postsynaptic calcium influx via L-type channels for the induction of long-term potentiation (LTP) of mossy fiber input to CA3 pyramidal neurons was tested for two different patterns of stimulation. Two types of LTP-inducing stimuli were used based on the suggestion that one of them, brief high-frequency stimulation (B-HFS), induces LTP postsynaptically, whereas the other pattern, long high-frequency stimulation (L-HFS), induces mossy fiber LTP presynaptically. To test whether or not calcium influx into CA3 pyramidal neurons is necessary for LTP induced by either pattern of stimulation, nimodipine, a L-type calcium channel antagonist, was added during stimulation. In these experiments nimodipine blocked the induction of mossy fiber LTP when B-HFS was given [34 ± 5% (mean ± SE) increase in control versus 7 ± 4% in nimodipine, P < 0.003]; in contrast, nimodipine did not block the induction of LTP with L-HFS (107 ± 10% in control vs. 80 ± 9% in nimodipine, P > 0.05). Administration of nimodipine after the induction of LTP had no effect on the expression of LTP. In addition, B- and L-HFS delivered directly to commissural/associational fibers in stratum radiatum failed to induce a N-methyl-d-aspartate-independent form of LTP, obviating the possibility that the presumed mossy fiber LTP resulted from potentiation of other synapses. Nimodipine had no effect on calcium transients recorded from mossy fiber presynaptic terminals evoked with the B-HFS paradigm but reduced postsynaptic calcium transients. Our results support the hypothesis that induction of mossy fiber LTP by B-HFS is mediated postsynaptically and requires entry of calcium through L-type channels into CA3 neurons.

scholarly journals The intellectual disability gene Kirrel3 regulates target-specific mossy fiber synapse development in the hippocampus

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
E Anne Martin ◽  
Shruti Muralidhar ◽  
Zhirong Wang ◽  
Diégo Cordero Cervantes ◽  
Raunak Basu ◽  
...  
Keyword(s):  
Synapse Formation ◽  
Mossy Fiber ◽  
Neuron Activity ◽  
Target Cells ◽  
Synaptic Changes ◽  
Mossy Fiber Synapse ◽  
Ca3 Neurons ◽  
Circuit Function ◽  
Feed Forward Inhibition

Synaptic target specificity, whereby neurons make distinct types of synapses with different target cells, is critical for brain function, yet the mechanisms driving it are poorly understood. In this study, we demonstrate Kirrel3 regulates target-specific synapse formation at hippocampal mossy fiber (MF) synapses, which connect dentate granule (DG) neurons to both CA3 and GABAergic neurons. Here, we show Kirrel3 is required for formation of MF filopodia; the structures that give rise to DG-GABA synapses and that regulate feed-forward inhibition of CA3 neurons. Consequently, loss of Kirrel3 robustly increases CA3 neuron activity in developing mice. Alterations in the Kirrel3 gene are repeatedly associated with intellectual disabilities, but the role of Kirrel3 at synapses remained largely unknown. Our findings demonstrate that subtle synaptic changes during development impact circuit function and provide the first insight toward understanding the cellular basis of Kirrel3-dependent neurodevelopmental disorders.

scholarly journals Synapse type-specific proteomic dissection identifies IgSF8 as a hippocampal CA3 microcircuit organizer

2019 ◽  
Author(s):  
Nuno Apóstolo ◽  
Samuel N. Smukowski ◽  
Jeroen Vanderlinden ◽  
Giuseppe Condomitti ◽  
Vasily Rybakin ◽  
...  
Keyword(s):  
Cell Surface ◽  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Surface Protein ◽  
Guidance Cue ◽  
Hippocampal Ca3 ◽  
Cell Surface Interactions ◽  
Ca3 Pyramidal Neurons ◽  
Ca3 Neurons ◽  
Multiple Ligand

SummarySynaptic diversity is a key feature of neural circuits. The structural and functional diversity of closely spaced inputs converging on the same neuron suggests that cell-surface interactions are essential in organizing input properties. Here, we analyzed the cell-surface protein (CSP) composition of hippocampal mossy fiber (MF) inputs on CA3 pyramidal neurons to identify regulators of MF-CA3 synapse properties. We uncover a rich cell-surface repertoire that includes adhesion proteins, guidance cue receptors, extracellular matrix (ECM) proteins, and uncharacterized CSPs. Interactome screening reveals multiple ligand-receptor modules and identifies ECM protein Tenascin-R (TenR) as a ligand of the uncharacterized neuronal receptor IgSF8. Presynaptic Igsf8 deletion impairs MF-CA3 synaptic architecture and robustly decreases the density of bouton filopodia that provide feedforward inhibition of CA3 neurons. Consequently, loss of IgSF8 increases CA3 neuron excitability. Our findings identify IgSF8 as a regulator of CA3 microcircuit development and suggest that combinations of CSP modules define input identity.

scholarly journals Early Ischemia Enhances Action Potential-Dependent, Spontaneous Glutamatergic Responses in CA1 Neurons

2009 ◽  
Vol 30 (3) ◽  
pp. 555-565 ◽  
Author(s):  
Hui Ye ◽  
Shirin Jalini ◽  
Liang Zhang ◽  
Milton Charlton ◽  
Peter L Carlen
Keyword(s):  
Action Potential ◽  
Pyramidal Neurons ◽  
Glutamate Release ◽  
Brain Slices ◽  
Spontaneous Release ◽  
Ca1 Neurons ◽  
Relative Contribution ◽  
Hippocampal Ca1 ◽  
Ca3 Neurons

Two types of quantal spontaneous neurotransmitter release are present in the nervous system, namely action potential (AP)-dependent release and AP-independent release. Previous studies have identified and characterized AP-independent release during hypoxia and ischemia. However, the relative contribution of AP-dependent spontaneous release to the overall glutamate released during transient ischemia has not been quantified. Furthermore, the neuronal activity that mediates such release has not been identified. Using acute brain slices, we show that AP-dependent release constitutes approximately one-third of the overall glutamate-mediated excitatory postsynaptic potentials/currents (EPSPs/EPSCs) measured onto hippocampal CA1 pyramidal neurons. However, during transient (2 mins) in vitro hypoxia–hypoglycemia, large-amplitude, AP-dependent spontaneous release is significantly enhanced and contributes to 74% of the overall glutamatergic responses. This increased AP-dependent release is due to hyper-excitability in the presynaptic CA3 neurons, which is mediated by the activity of NMDA receptors. Spontaneous glutamate release during ischemia can lead to excitotoxicity and perturbation of neural network functions.

scholarly journals Differences in Nicotine Encoding Dopamine Release between the Striatum and Shell Portion of the Nucleus Accumbens

2018 ◽  
Vol 28 (3) ◽  
pp. 248-261 ◽  
Author(s):  
Yuan-Hao Chen ◽  
Bon-Jour Lin ◽  
Tsung-Hsun Hsieh ◽  
Tung-Tai Kuo ◽  
Jonathan Miller ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
High Frequency ◽  
Dopamine Release ◽  
Brain Slices ◽  
Dorsal Striatum ◽  
High Frequency Stimulation ◽  
Sprague Dawley ◽  
Frequency Stimulation ◽  
Da Release

The aim of this work was to determine the effect of nicotine desensitization on dopamine (DA) release in the dorsal striatum and shell of the nucleus accumbens (NAc) from brain slices. In vitro fast-scan cyclic voltammetry analysis was used to evaluate dopamine release in the dorsal striatum and the NAc shell of Sprague–Dawley rats after infusion of nicotine, a nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (Mec), and an α4β2 cholinergic receptor antagonist (DHβe). DA release related to nicotine desensitization in the striatum and NAc shell was compared. In both structures, tonic release was suppressed by inhibition of the nicotine receptor (via Mec) and the α4β2 receptor (via DHβe). Paired-pulse ratio (PPR) was facilitated in both structures after nicotine and Mec infusion, and this facilitation was suppressed by increasing the stimulation interval. After variable frequency stimulation (simulating phasic burst), nicotine infusion induced significant augmentation of DA release in the striatum that was not seen in the absence of nicotine. In contrast, nicotine reduced phasic DA release in NAc, although frequency augmentation was seen both with and without nicotine. Evaluation of DA release evoked by various trains (high-frequency stimulation (HFS) 100 Hz) of high-frequency stimulation revealed significant enhancement after a train of three or more pulses in the striatum and NAc. The concentration differences between tonic and phasic release related to nicotine desensitization were more pronounced in the NAc shell. Nicotine desensitization is associated with suppression of tonic release of DA in both the striatum and NAc shell that may occur via the α4β2 subtype of nAChR, whereas phasic frequency-dependent augmentation and HFS-related gating release is more pronounced in the striatum than in the NAc shell. Differences between phasic and tonic release associated with nicotine desensitization may underlie processing of reward signals in the NAc shell, and this may have major implications for addictive behavior.

scholarly journals LTD at mossy fiber synapses onto stratum lucidum interneurons requires TrkB and retrograde endocannabinoid signaling

2019 ◽  
Vol 121 (2) ◽  
pp. 609-619 ◽  
Author(s):  
Enhui Pan ◽  
Zirun Zhao ◽  
James O. McNamara
Keyword(s):  
High Frequency ◽  
Mossy Fiber ◽  
Mossy Fibers ◽  
High Frequency Stimulation ◽  
Long Term Depression ◽  
Stratum Lucidum ◽  
Frequency Stimulation ◽  
Retrograde Signal ◽  
Stimulation Of

Hippocampal mossy fiber axons simultaneously activate CA3 pyramidal cells and stratum lucidum interneurons (SLINs), the latter providing feedforward inhibition to control CA3 pyramidal cell excitability. Filopodial extensions of giant boutons of mossy fibers provide excitatory synaptic input to the SLIN. These filopodia undergo extraordinary structural plasticity causally linked to execution of memory tasks, leading us to seek the mechanisms by which activity regulates these synapses. High-frequency stimulation of the mossy fibers induces long-term depression (LTD) of their calcium-permeable AMPA receptor synapses with SLINs; previous work localized the site of induction to be postsynaptic and the site of expression to be presynaptic. Yet, the underlying signaling events and the identity of the retrograde signal are incompletely understood. We used whole cell recordings of SLINs in hippocampal slices from wild-type and mutant mice to explore the mechanisms. Genetic and pharmacologic perturbations revealed a requirement for both the receptor tyrosine kinase TrkB and its agonist, brain-derived neurotrophic factor (BDNF), for induction of LTD. Inclusion of inhibitors of Trk receptor kinase and PLC in the patch pipette prevented LTD. Endocannabinoid receptor antagonists and genetic deletion of the CB1 receptor prevented LTD. We propose a model whereby release of BDNF from mossy fiber filopodia activates TrkB and PLCγ1 signaling postsynaptically within SLINs, triggering synthesis and release of an endocannabinoid that serves as a retrograde signal, culminating in reduced glutamate release. Insights into the signaling pathways by which activity modifies function of these synapses will facilitate an understanding of their contribution to the local circuit and behavioral consequences of hippocampal granule cell activity. NEW & NOTEWORTHY We investigated signaling mechanisms underlying plasticity of the hippocampal mossy fiber filopodial synapse with interneurons in stratum lucidum. High-frequency stimulation of the mossy fibers induces long-term depression of this synapse. Our findings are consistent with a model in which brain-derived neurotrophic factor released from filopodia activates TrkB of a stratum lucidum interneuron; the ensuing activation of PLCγ1 induces synthesis of an endocannabinoid, which provides a retrograde signal leading to reduced release of glutamate presynaptically.

Quantal mechanism of long-term potentiation in hippocampal mossy-fiber synapses

1994 ◽  
Vol 71 (6) ◽  
pp. 2552-2556 ◽  
Author(s):  
Z. Xiang ◽  
A. C. Greenwood ◽  
E. W. Kairiss ◽  
T. H. Brown
Keyword(s):  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Classical Method ◽  
Brain Slices ◽  
Long Term Potentiation ◽  
Quantal Size ◽  
Term Potentiation ◽  
Before And After ◽  
Whole Cell Recordings

1. The quantal mechanism underlying the expression of long-term potentiation (LTP) was studied in the mossy-fiber (mf) synapses of the rat hippocampus. Whole-cell recordings were used to measure the excitatory postsynaptic currents (EPSCs) before and after LTP induction in brain slices maintained at 31 +/- 1 degrees C. 2. Evoked EPSCs were recorded from 473 CA3 pyramidal neurons. The mf synapses were stimulated using paired pulses (40-ms interpulse interval) repeated every 2–10 s. At least 400 pairs of mf responses were obtained before and during the expression of LTP, which was produced by high-frequency (100 Hz) mf stimulation. Sufficiently stationary data were obtained from five neurons that exhibited LTP and that also satisfied strict criteria and procedures that are necessary for eliciting and identifying unitary mf responses. 3. Three independent lines of evidence implicated a presynaptic component to the mechanism underlying mf LTP. The first was based on a graphical version of the classical method of variance. The graphical variance (GV) method was evaluated by clamping the cell at two different holding potentials during paired-pulse facilitation (PPF). The results indicated that the GV method can distinguish changes in mean quantal content m and mean quantal size q in rat mf synapses. The same analysis, when applied to PPF before and after LTP induction, indicated that both result from an increase in m. 4. The second line of evidence was based on the classical method of failures. Consistent with the inference that mf LTP is due to an increase in m, there was a statistically significant reduction in the number of quantal release failures.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellular Mechanisms Preventing Sustained Activation of Cortex During Subcortical High-Frequency Stimulation

2006 ◽  
Vol 96 (2) ◽  
pp. 613-621 ◽  
Author(s):  
Karl J. Iremonger ◽  
Trent R. Anderson ◽  
Bin Hu ◽  
Zelma H. T. Kiss
Keyword(s):  
Motor Cortex ◽  
High Frequency ◽  
Cortical Neurons ◽  
Primary Motor Cortex ◽  
Brain Slices ◽  
Subcortical White Matter ◽  
High Frequency Stimulation ◽  
Cellular Mechanisms ◽  
Ventral Thalamus ◽  
Frequency Stimulation

Axonal excitation has been proposed as a key mechanism in therapeutic brain stimulation. In this study we examined how high-frequency stimulation (HFS) of subcortical white matter tracts projecting to motor cortex affects downstream postsynaptic responses in cortical neurons. Whole cell recordings were performed in the primary motor cortex (M1) and ventral thalamus of rat brain slices. In M1, neurons showed only an initial depolarization in response to HFS, after which the membrane potential returned to prestimulation levels. The prolonged suppression of excitation during stimulation was neither associated with GABAergic inhibition nor complete action potential failure in stimulated axons. Instead we found that HFS caused a depression of excitatory synaptic currents in postsynaptic neurons that was specific to the stimulated subcortical input. These data are consistent with the hypothesis that axonal HFS produces a functional deafferentation of postsynaptic targets likely from depletion of neurotransmitter.

Sign in / Sign up

Export Citation Format

Share Document