scholarly journals LRRTM3 regulates activity-dependent synchronization of synapse properties in topographically connected hippocampal neural circuits

2022 ◽  
Vol 119 (3) ◽  
pp. e2110196119
Author(s):  
Jinhu Kim ◽  
Dongseok Park ◽  
Na-Young Seo ◽  
Taek-Han Yoon ◽  
Gyu Hyun Kim ◽  
...  
Keyword(s):  
Neural Circuits ◽  
Mossy Fiber ◽  
Transmembrane Protein ◽  
Long Term Potentiation ◽  
Excitatory Synapse ◽  
Granule Neurons ◽  
Structural And Functional Properties ◽  
Ca3 Neurons ◽  
Activity Dependent ◽  
Deficient Mice

Synaptic cell-adhesion molecules (CAMs) organize the architecture and properties of neural circuits. However, whether synaptic CAMs are involved in activity-dependent remodeling of specific neural circuits is incompletely understood. Leucine-rich repeat transmembrane protein 3 (LRRTM3) is required for the excitatory synapse development of hippocampal dentate gyrus (DG) granule neurons. Here, we report that Lrrtm3-deficient mice exhibit selective reductions in excitatory synapse density and synaptic strength in projections involving the medial entorhinal cortex (MEC) and DG granule neurons, accompanied by increased neurotransmitter release and decreased excitability of granule neurons. LRRTM3 deletion significantly reduced excitatory synaptic innervation of hippocampal mossy fibers (Mf) of DG granule neurons onto thorny excrescences in hippocampal CA3 neurons. Moreover, LRRTM3 loss in DG neurons significantly decreased mossy fiber long-term potentiation (Mf-LTP). Remarkably, silencing MEC–DG circuits protected against the decrease in the excitatory synaptic inputs onto DG and CA3 neurons, excitability of DG granule neurons, and Mf-LTP in Lrrtm3-deficient mice. These results suggest that LRRTM3 may be a critical factor in activity-dependent synchronization of the topography of MEC–DG–CA3 excitatory synaptic connections. Collectively, our data propose that LRRTM3 shapes the target-specific structural and functional properties of specific hippocampal circuits.

Voltage-clamp analysis of synaptic inhibition during long-term potentiation in hippocampus

1986 ◽  
Vol 55 (4) ◽  
pp. 767-775 ◽  
Author(s):  
W. H. Griffith ◽  
T. H. Brown ◽  
D. Johnston
Keyword(s):  
Voltage Clamp ◽  
Mossy Fiber ◽  
Long Term Potentiation ◽  
Synaptic Efficacy ◽  
Synaptic Response ◽  
Inhibitory Component ◽  
Mixed Response ◽  
Term Potentiation ◽  
Ca3 Neurons

The excitatory synaptic response evoked by stimulating the mossy fiber synaptic input to hippocampal CA3 neurons in normally accompanied by concomitant feedforward or recurrent inhibition. The purpose of the present study was to determine whether a decrease in the inhibitory conductance of this mixed synaptic response contributes to the enhanced synaptic efficacy observed during long-term potentiation (LTP). Intracellular recordings were made from CA3 neurons of rat hippocampal brain slices. Current- and voltage-clamp measurements of the mixed excitatory/inhibitory evoked synaptic response were made, using a single-electrode clamp system. Outward and inward rectification were reduced, respectively, by intracellular injection and bath application of Cs+. Biophysical analysis of the evoked synaptic conductance sequence was performed before and 15 min to 1 h after inducing LTP. As expected, measurements made in the early part of the conductance sequence, which represents primarily the monosynaptic excitatory input, demonstrated an increase in the slope conductance during LTP. Measurements made later in the conductance sequence, when the excitatory component appeared to have declined to a negligible value, revealed no decrease in the slope conductance of the inhibitory component of the mixed response. We conclude that a decrease in the conductance associated with the inhibitory component of the mixed synaptic response plays little or no role in the increase in synaptic efficacy observed during LTP of this synaptic system.

scholarly journals Postsynaptic Expression of a New Calcium Pathway in Hippocampal CA3 Neurons and Its Influence on Mossy Fiber Long-Term Potentiation

2002 ◽  
Vol 22 (11) ◽  
pp. 4312-4320 ◽  
Author(s):  
Wataru Kakegawa ◽  
Nobuaki Yamada ◽  
Masae Iino ◽  
Kimihiko Kameyama ◽  
Tatsuya Umeda ◽  
...  
Keyword(s):  
Mossy Fiber ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Hippocampal Ca3 ◽  
Ca3 Neurons

scholarly journals Long-term depression at hippocampal mossy fiber-CA3 synapses involves BDNF but is not mediated by p75NTR signaling

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Machhindra Garad ◽  
Elke Edelmann ◽  
Volkmar Leßmann
Keyword(s):  
Synaptic Plasticity ◽  
Mossy Fiber ◽  
Plasminogen Activator Inhibitor ◽  
Long Term Potentiation ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Long Term Depression ◽  
Ca3 Neurons

AbstractBDNF plays a crucial role in the regulation of synaptic plasticity. It is synthesized as a precursor (proBDNF) that can be proteolytically cleaved to mature BDNF (mBDNF). Previous studies revealed a bidirectional mode of BDNF actions, where long-term potentiation (LTP) was mediated by mBDNF through tropomyosin related kinase (Trk) B receptors whereas long-term depression (LTD) depended on proBDNF/p75 neurotrophin receptor (p75NTR) signaling. While most experimental evidence for this BDNF dependence of synaptic plasticity in the hippocampus was derived from Schaffer collateral (SC)-CA1 synapses, much less is known about the mechanisms of synaptic plasticity, in particular LTD, at hippocampal mossy fiber (MF) synapses onto CA3 neurons. Since proBDNF and mBDNF are expressed most abundantly at MF-CA3 synapses in the rodent brain and we had shown previously that MF-LTP depends on mBDNF/TrkB signaling, we now explored the role of proBDNF/p75NTR signaling in MF-LTD. Our results show that neither acute nor chronic inhibition of p75NTR signaling impairs MF-LTD, while short-term plasticity, in particular paired-pulse facilitation, at MF-CA3 synapses is affected by a lack of functional p75NTR signaling. Furthermore, MF-CA3 synapses showed normal LTD upon acute inhibition of TrkB receptor signaling. Nonetheless, acute inhibition of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of both intracellular and extracellular proBDNF cleavage, impaired MF-LTD. This seems to indicate that LTD at MF-CA3 synapses involves BDNF, however, MF-LTD does not depend on p75NTRs. Altogether, our experiments demonstrate that p75NTR signaling is not warranted for all glutamatergic synapses but rather needs to be checked separately for every synaptic connection.

scholarly journals Activity-dependent regulation of synaptic strength by PSD-95 in CA1 neurons

2012 ◽  
Vol 107 (4) ◽  
pp. 1058-1066 ◽  
Author(s):  
Peng Zhang ◽  
John E. Lisman
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Synaptic Strength ◽  
Ca1 Neurons ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Term Potentiation ◽  
Activity Dependent

CaMKII and PSD-95 are the two most abundant postsynaptic proteins in the postsynaptic density (PSD). Overexpression of either can dramatically increase synaptic strength and saturate long-term potentiation (LTP). To do so, CaMKII must be activated, but the same is not true for PSD-95; expressing wild-type PSD-95 is sufficient. This raises the question of whether PSD-95's effects are simply an equilibrium process [increasing the number of AMPA receptor (AMPAR) slots] or whether activity is somehow involved. To examine this question, we blocked activity in cultured hippocampal slices with TTX and found that the effects of PSD-95 overexpression were greatly reduced. We next studied the type of receptors involved. The effects of PSD-95 were prevented by antagonists of group I metabotropic glutamate receptors (mGluRs) but not by antagonists of ionotropic glutamate receptors. The inhibition of PSD-95-induced strengthening was not simply a result of inhibition of PSD-95 synthesis. To understand the mechanisms involved, we tested the role of CaMKII. Overexpression of a CaMKII inhibitor, CN19, greatly reduced the effect of PSD-95. We conclude that PSD-95 cannot itself increase synaptic strength simply by increasing the number of AMPAR slots; rather, PSD-95's effects on synaptic strength require an activity-dependent process involving mGluR and CaMKII.

How Synaptic Release Probability Shapes Neuronal Transmission: Information-Theoretic Analysis in a Cerebellar Granule Cell

2010 ◽  
Vol 22 (8) ◽  
pp. 2031-2058 ◽  
Author(s):  
Angelo Arleo ◽  
Thierry Nieus ◽  
Michele Bezzi ◽  
Anna D'Errico ◽  
Egidio D'Angelo ◽  
...  
Keyword(s):  
Information Transmission ◽  
Numerical Simulations ◽  
Granule Cell ◽  
Mossy Fiber ◽  
Dendritic Tree ◽  
Long Term Potentiation ◽  
Cerebellar Granule Cell ◽  
Information Theoretic ◽  
Cerebellar Granule ◽  
Release Probability

A nerve cell receives multiple inputs from upstream neurons by way of its synapses. Neuron processing functions are thus influenced by changes in the biophysical properties of the synapse, such as long-term potentiation (LTP) or depression (LTD). This observation has opened new perspectives on the biophysical basis of learning and memory, but its quantitative impact on the information transmission of a neuron remains partially elucidated. One major obstacle is the high dimensionality of the neuronal input-output space, which makes it unfeasible to perform a thorough computational analysis of a neuron with multiple synaptic inputs. In this work, information theory was employed to characterize the information transmission of a cerebellar granule cell over a region of its excitatory input space following synaptic changes. Granule cells have a small dendritic tree (on average, they receive only four mossy fiber afferents), which greatly bounds the input combinatorial space, reducing the complexity of information-theoretic calculations. Numerical simulations and LTP experiments quantified how changes in neurotransmitter release probability (p) modulated information transmission of a cerebellar granule cell. Numerical simulations showed that p shaped the neurotransmission landscape in unexpected ways. As p increased, the optimality of the information transmission of most stimuli did not increase strictly monotonically; instead it reached a plateau at intermediate p levels. Furthermore, our results showed that the spatiotemporal characteristics of the inputs determine the effect of p on neurotransmission, thus permitting the selection of distinctive preferred stimuli for different p values. These selective mechanisms may have important consequences on the encoding of cerebellar mossy fiber inputs and the plasticity and computation at the next circuit stage, including the parallel fiber–Purkinje cell synapses.

The Vertical Lobe of Cephalopods

2017 ◽  
pp. 558-574 ◽  
Author(s):  
Ana Turchetti-Maia ◽  
Tal Shomrat ◽  
Binyamin Hochner
Keyword(s):  
Complex Networks ◽  
Long Term Potentiation ◽  
Learning Networks ◽  
Neuronal Circuitry ◽  
Cellular Processes ◽  
Term Potentiation ◽  
Matrix Organization ◽  
Activity Dependent ◽  
Similar Organization

We show that the cephalopod vertical lobe (VL) is a promising system for assessing the function and organization of the neuronal circuitry mediating complex learning and memory behavior. Studies in octopus and cuttlefish VL networks suggest an independent evolutionary convergence into a matrix organization of a divergence-convergence (“fan-out fan-in”) network with activity-dependent long-term plasticity mechanisms. These studies also show, however, that the properties of the neurons, neurotransmitters, neuromodulators, and mechanisms of induction and maintenance of long-term potentiation are different from those evolved in vertebrates and other invertebrates, and even highly variable among these two cephalopod species. This suggests that complex networks may have evolved independently multiple times and that, even though memory and learning networks share similar organization and cellular processes, there are many molecular ways of constructing them.

Effects of Adult Neurogenesis on Synaptic Plasticity in the Rat Dentate Gyrus

2001 ◽  
Vol 85 (6) ◽  
pp. 2423-2431 ◽  
Author(s):  
J. S. Snyder ◽  
N. Kee ◽  
J. M. Wojtowicz
Keyword(s):  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Adult Neurogenesis ◽  
Long Term Potentiation ◽  
Receptor Blocker ◽  
Granule Neurons ◽  
Term Potentiation ◽  
Cell Recording ◽  
Similar Preparation ◽  
Nmda Receptor Blocker

Ongoing neurogenesis in the adult hippocampal dentate gyrus (DG) generates a substantial population of young neurons. This phenomenon is present in all species examined thus far, including humans. Although the regulation of adult neurogenesis by various physiologically relevant factors such as learning and stress has been documented, the functional contributions of the newly born neurons to hippocampal functions are not known. We investigated possible contributions of the newly born granule neurons to synaptic plasticity in the hippocampal DG. In the standard hippocampal slice preparation perfused with artificial cerebrospinal fluid (ACSF), a small (10%) long-term potentiation (LTP) of the evoked field potentials is seen after tetanic stimulation of the afferent medial perforant pathway (MPP). The induction of this ACSF-LTP is resistant to a N-methyl-d-aspartate (NMDA) receptor blocker,d,l-2-amino-5-phosphonovaleric acid (APV), but is completely prevented by ifenprodil, a blocker of NR2B subtype of NMDA receptors. In contrast, slices perfused with picrotoxin (PICRO), a GABA-receptor blocker, revealed a larger (40–50%), APV-sensitive but ifenprodil-insensitive LTP. The ACSF-LTP required lower frequency of stimulation and fewer stimuli for its induction than the PICRO-LTP. All these characteristics of ACSF-LTP are in agreement with the properties of the putative individual new granule neurons examined previously with the use of the whole cell recording technique in a similar preparation. A causal relationship between neurogenesis and ACSF-LTP was confirmed in experiments using low dose of gamma radiation applied to the brain 3 wk prior to the electrophysiological experiments. In these experiments, the new cell proliferation was drastically reduced and ACSF-LTP was selectively blocked. We conclude that the young, adult-generated granule neurons play a significant role in synaptic plasticity in the DG. Since DG is the major source of the afferent inputs into the hippocampus, the production and the plasticity of new neurons may have an important role in the hippocampal functions such as learning and memory.

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