Flip side of synaptic plasticity: Long-term depression mechanisms in the hippocampus

1. Activation of sensory neurons at 2 Hz for 15 min induces long-term depression (LTD) of isolated Aplysia sensorimotor synapses in cell culture. 2. Prior infusion of the Ca2+ chelator 1,2-bis-(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA) into the postsynaptic motor neuron blocks the induction of LTD, but not short-term synaptic depression. 3. Invertebrate central synapses possess the capacity for LTD. This form of long-term synaptic plasticity may play an important role in learning in Aplysia.

Download Full-text

Dissecting the Roles of Kalirin-7/PSD-95/GluN2B Interactions in Different Forms of Synaptic Plasticity

10.21203/rs.3.rs-41613/v1 ◽

2020 ◽

Author(s):

Mason L. Yeh ◽

Jessica R Yasko ◽

Eric S. Levine ◽

Betty A. Eipper ◽

Richard Mains

Keyword(s):

Synaptic Plasticity ◽

Molecular Mechanisms ◽

Long Term Potentiation ◽

Surface Expression ◽

Synaptic Function ◽

Nucleotide Exchange ◽

Long Term Depression ◽

Term Potentiation ◽

Knockout Animals

Abstract Background: Kalirin-7 (Kal7) is a multidomain scaffold and guanine nucleotide exchange factor localized to the postsynaptic density, where Kal7 is crucial for synaptic plasticity. Kal7 knockout mice exhibit marked suppression of long-term potentiation and long-term depression in hippocampus, cerebral cortex and spinal cord, with depressed surface expression of GluN2B receptor subunits and dramatically blunted perception of pain. Kal7 knockout animals show exaggerated locomotor responses to psychostimulants and self-administer cocaine more enthusiastically than wildtype mice. Results: To address the underlying cellular and molecular mechanisms which are deranged by loss of Kal7, we infused candidate intracellular interfering peptides to acutely challenge the synaptic function(s) of Kal7 with potential protein binding partners, to determine if plasticity deficits in Kal7-/- mice are the product of developmental processes since conception, or could be produced on a much shorter time scale. We demonstrated that these small intracellular peptides disrupted normal long-term potentiation and long-term depression, strongly suggesting that maintenance of established interactions of Kal7 with PSD-95 and/or GluN2B is crucial to synaptic plasticity. Conclusions: Blockade of the Kal7-GluN2B interaction was most effective at blocking long-term potentiation, but had no effect on long-term depression. Biochemical approaches indicated that Kal7 interacted with PSD-95 at multiple sites within Kal7.

Download Full-text

Endocannabinoid dynamics gate spike-timing dependent depression and potentiation

eLife ◽

10.7554/elife.13185 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 24

Author(s):

Yihui Cui ◽

Ilya Prokin ◽

Hao Xu ◽

Bruno Delord ◽

Stephane Genet ◽

...

Keyword(s):

Mathematical Modeling ◽

Synaptic Plasticity ◽

Learning And Memory ◽

Long Term Potentiation ◽

Cellular Mechanism ◽

Spike Timing ◽

Long Term Depression ◽

Term Potentiation ◽

Short And Long Term

Synaptic plasticity is a cardinal cellular mechanism for learning and memory. The endocannabinoid (eCB) system has emerged as a pivotal pathway for synaptic plasticity because of its widely characterized ability to depress synaptic transmission on short- and long-term scales. Recent reports indicate that eCBs also mediate potentiation of the synapse. However, it is not known how eCB signaling may support bidirectionality. Here, we combined electrophysiology experiments with mathematical modeling to question the mechanisms of eCB bidirectionality in spike-timing dependent plasticity (STDP) at corticostriatal synapses. We demonstrate that STDP outcome is controlled by eCB levels and dynamics: prolonged and moderate levels of eCB lead to eCB-mediated long-term depression (eCB-tLTD) while short and large eCB transients produce eCB-mediated long-term potentiation (eCB-tLTP). Moreover, we show that eCB-tLTD requires active calcineurin whereas eCB-tLTP necessitates the activity of presynaptic PKA. Therefore, just like glutamate or GABA, eCB form a bidirectional system to encode learning and memory.

Download Full-text

Long-Term Potentiation and Long-Term Depression

Oxford Research Encyclopedia of Neuroscience ◽

10.1093/acrefore/9780190264086.013.148 ◽

2018 ◽

Cited By ~ 1

Author(s):

Arianna Maffei

Keyword(s):

Synaptic Plasticity ◽

Neural Circuit ◽

Long Term Potentiation ◽

Synaptic Connections ◽

Long Term Depression ◽

Term Potentiation ◽

Functional Implications ◽

The Brain

Synaptic connections in the brain can change their strength in response to patterned activity. This ability of synapses is defined as synaptic plasticity. Long lasting forms of synaptic plasticity, long-term potentiation (LTP), and long-term depression (LTD), are thought to mediate the storage of information about stimuli or features of stimuli in a neural circuit. Since its discovery in the early 1970s, synaptic plasticity became a central subject of neuroscience, and many studies centered on understanding its mechanisms, as well as its functional implications.

Download Full-text

Persistent memories of long-term potentiation and the N-methyl-d-aspartate receptor

Brain and Neuroscience Advances ◽

10.1177/2398212819848213 ◽

2019 ◽

Vol 3 ◽

pp. 239821281984821 ◽

Cited By ~ 7

Author(s):

TVP Bliss ◽

GL Collingridge

Keyword(s):

Synaptic Plasticity ◽

Long Term Potentiation ◽

Brain Disorders ◽

Molecular Pharmacology ◽

Cellular Mechanisms ◽

Long Term Depression ◽

Aspartate Receptor ◽

Term Potentiation ◽

Core Feature

In this article, we describe our involvement in the early days of research into long-term potentiation. We start with a description of the early experiments conducted in Oslo and London where long-term potentiation was first characterised. We discuss the ways in which the molecular pharmacology of glutamate receptors control the induction and expression of long-term potentiation and its counterpart, long-term depression. We then go on to summarise the extraordinary advances in understanding the cellular mechanisms of synaptic plasticity that have taken place in the subsequent half century. Finally, the increasing evidence that impaired long-term potentiation is a core feature of many brain disorders (LToPathies) is addressed by way of a few selected examples.

Download Full-text

Dynamic Data-based Modelling of Synaptic Plasticity: mGluR-dependent Long-term Depression

Proceedings of the International Conference on Bio-inspired Systems and Signal Processing ◽

10.5220/0004231100480053 ◽

2013 ◽

Keyword(s):

Synaptic Plasticity ◽

Long Term Depression ◽

Dynamic Data

Download Full-text

System Identification of mGluR-Dependent Long-Term Depression

Neural Computation ◽

10.1162/neco_a_00408 ◽

2013 ◽

Vol 25 (3) ◽

pp. 650-670 ◽

Cited By ~ 5

Author(s):

Tim Tambuyzer ◽

Tariq Ahmed ◽

C. James Taylor ◽

Daniel Berckmans ◽

Detlef Balschun ◽

...

Keyword(s):

Synaptic Plasticity ◽

System Identification ◽

Metabotropic Glutamate Receptor ◽

Synaptic Function ◽

Long Term Depression ◽

Metabotropic Glutamate ◽

Powerful Approach ◽

Underlying Mechanisms ◽

First Time

Recent advances have started to uncover the underlying mechanisms of metabotropic glutamate receptor (mGluR)–dependent long-term depression (LTD). However, it is not completely clear how these mechanisms are linked, and it is believed that several crucial mechanisms remain to be revealed. In this study, we investigated whether system identification (SI) methods can be used to gain insight into the mechanisms of synaptic plasticity. SI methods have been shown to be an objective and powerful approach for describing how sensory neurons encode information about stimuli. However, to our knowledge, it is the first time that SI methods have been applied to electrophysiological brain slice recordings of synaptic plasticity responses. The results indicate that the SI approach is a valuable tool for reverse-engineering of mGluR-LTD responses. We suggest that such SI methods can aid in unraveling the complexities of synaptic function.

Download Full-text

Metabotropic glutamate receptors and visual cortical synaptic plasticity

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y95-186 ◽

1995 ◽

Vol 73 (9) ◽

pp. 1312-1322 ◽

Cited By ~ 13

Author(s):

T. Kamishita ◽

H. Haruta ◽

N. Torii ◽

T. Tsumoto ◽

T. P. Hicks

Keyword(s):

Synaptic Plasticity ◽

Visual Cortex ◽

Metabotropic Glutamate Receptors ◽

Excitatory Amino Acid ◽

Long Term Potentiation ◽

Receptor Subtype ◽

Long Term Depression ◽

Metabotropic Receptor ◽

Term Potentiation

Two forms of use-dependent synaptic plasticity, called long-term potentiation (LTP) and long-term depression (LTD), can be elicited in the visual cortex following different paradigms of electrophysiological stimulation. These neurobiological phenomena often are considered as necessary components of models for the alteration in function of the nervous system that must occur at some level for the establishment and (or) maintenance of memory engrams, for learning processes, or for the consolidation of active neural connections and regression of inactive contacts in the developing brain. It has been postulated that for LTP and LTD to be produced in the hippocampus, activation of a particular subtype of excitatory amino acid receptor, the metabotropic receptor, is a critical requirement. Only recently has it become possible to test this hypothesis directly, as a new compound, (±)-α-methyl-4-carboxyphenylglycine (MCPG), has been introduced and the suggestion made that it selectively antagonizes the metabotropic receptor. This substance has been tested in the present study on responses recorded from slices of rat visual cortex and has been found both to block the activation of the metabotropic receptor and to interfere selectively with the form of synaptic plasticity called LTD. It thus appears from the experiments reported in this paper as though the metabotropic receptor subtype that is blocked by MCPG is required for the expression of LTD but not for the expression of LTP, in the visual cortex of adult rats.Key words: excitatory amino acids, long-term potentiation, long-term depression, visual cortex, (±)-α-methyl-4-carboxyphenylglycine (MCPG).

Download Full-text