Matched Pre- and Post-Synaptic Changes Underlie Synaptic Plasticity over Long Time Scales

Jean-Vincent Le Bé, Henry Markram
Soc Neuroscience, 2013
Journal paper

Abstract

Modifications of synaptic efficacies are considered essential for learning and memory. However, it is not known how the underlying functional components of synaptic transmission change over long time scales. To address this question, we studied cortical synapses from young Wistar rats before and after 12 h intervals of spontaneous or glutamate-induced spiking activity. We found that, under these conditions, synaptic efficacies can increase or decrease by up to 10-fold. Statistical analyses reveal that these changes reflect modifications in the number of presynaptic release sites, together with postsynaptic changes that maintain the quantal size per release site. The quantitative relation between the presynaptic and postsynaptic transmission components was not affected when synaptic plasticity was enhanced or reduced using a broad range of pharmacological agents. These findings suggest that ongoing synaptic plasticity results in matched presynaptic and postsynaptic modifications, in which elementary modules that span the synaptic cleft are added or removed as a function of experience.

Official source

https://infoscience.epfl.ch/record/188847?ln=en

About this result

This page is automatically generated and may contain information that is not correct, complete, up-to-date, or relevant to your search query. The same applies to every other page on this website. Please make sure to verify the information with EPFL's official sources.

Related concepts

Related publications

Delayed and Temporally Imprecise Neurotransmission in Reorganizing Cortical Microcircuits

Anne Alison Jorstad, Graham Knott, Yan Liu

Synaptic neurotransmission is modified at cortical connections throughout life. Varying the amplitude of the postsynaptic response is one mechanism that generates flexible signaling in neural circuits. The timing of the synaptic response may also play a role. Here, we investigated whether weakening and loss of an entire connection between excitatory cortical neurons was foreshadowed in the timing of the postsynaptic response. We made electrophysiological recordings in rat primary somatosensory cortex that was undergoing experience-dependent loss of complete local excitatory connections. The synaptic latency of pyramid-pyramid connections, which typically comprise multiple synapses, was longer and more variable. Connection strength and latency were not correlated. Instead, prolonged latency was more closely related to progression of connection loss. The action potential waveform and axonal conduction velocity were unaffected, suggesting that the altered timing of neurotransmission was attributable to a synaptic mechanism. Modeling studies indicated that increasing the latency and jitter at a subset of synapses reduced the number of action potentials fired by a postsynaptic neuron. We propose that prolonged synaptic latency and diminished temporal precision of neurotransmission are hallmarks of impending loss of a cortical connection.

Soc Neuroscience2015

Synaptic plasticity is the ability of the connections between nerve cells, called synapses, to change in strength. The presence of a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors (AMPAR) at the synapse controls the strength of excitatory transmission and their number can be modulated. Controlled surface insertion of AMPA-type glutamate receptors and their lateral diffusion into synapses are proposed to be major mechanisms for the regulation of synaptic plasticity. Here we applied the recently established Acyl-Carrier-Protein-labeling technique in combination with lentiviral expression in hippocampal neurons to label individually ACP-tagged AMPA receptor subunits at the surface of neurons. This technique uses a carrier protein from the fatty acid synthesis and a mutant therof as a tag, which were fused by genetic engineering to the AMPAR subunits. The labeling procedure is specific for proteins, AMPARs in our case, which are present at the plasma membrane of the cell. We show that this technique allows to differentially label two subunits of the receptor. Moreover, these subunits are integrated into heteromeric receptors together with endogenous subunits, and these labeled receptors are targeted to functional synapses. The diffusion coefficient of labeled GluR2 at the surface of living neurons is significantly higher in GluR2/GluR3-infected neurons compared to GluR1/GluR2-infected neurons suggesting a higher mobility of GluR2/3 receptors compared to GluR1/2 receptors. Finally, in sequential labeling experiments we detected newly inserted receptor subunits colocalized with presynaptic markers. The GluR1 subunit displayed a faster kinetics of insertion compare to the other subunits. Internalized GluR2 receptors have been shown to accumulate in perinuclear late endosomes in HEK 293T cells. Moreover, we expressed and labeled surface tagged-GluR2 receptors in hippocampal slices, using similar labeling technique as ACP. High-resolution images, sub-difraction limited, of hippocampal neurons stained for GluR2 were acquired with an experimental scanning near-field optical microscopy (SNOM). Together our results strongly indicate that receptor insertion is faster for GluR1 and that insertion occurs at or in close vicinity of synapses in mature hippocampal neuron cultures.

EPFL2007

In vivo measurement of excitatory synaptic transmission between identified neurons in layer 2/3 mouse barrel cortex

Aurélie Pala

The neocortex is the most distinctive feature of the mammalian brain and it is considered to be the substrate of high-order cognitive functions. The nature and the arrangement of the diverse neuronal elements constituting its multiple areas have received longstanding attention. Progressively such anatomical and functional investigations are undertaken in the context of an intact living being. It offers the possibility of examining the role of particular areas, networks or even individual neurons during various behavioral states. Synaptic connectivity and synaptic transmission have been traditionally investigated in reduced preparations. Typically, electrophysiological and optical techniques have been used to control and record the propagation of electrical activity between two or more neurons in acute brain slices in vitro. The purpose of this thesis is the investigation of synaptic connectivity and synaptic transmission within the intact neocortex of the living mouse. Here I took advantage of the recent development of optogenetics, in combination with electrophysiology and two-photon microscopy to systematically and directly record synaptic transmission between a single excitatory neuron and two main types of GABAergic neurons in layer 2/3 of the mouse barrel cortex in vivo. Overall, I discovered stronger excitatory connections onto GABAergic neurons than onto excitatory neurons, irrespective of the absolute or relative locations of the pre- and postsynaptic neurons somas. I further revealed that parvalbumin-expressing (PV) and somatostatin-expressing (Sst) GABAergic neurons received excitatory inputs that were similar in magnitude, but were more reliable and faster in PV neurons than in Sst neurons. Exploring postsynaptic responses to multiple presynaptic action potentials elicited at high frequency, I found a strong short-term facilitation accompanied by significant input summation in Sst neurons, but little short-term dynamics with no summation in PV neurons. Lastly, I compared the amplitude of single action potential-evoked postsynaptic responses as a function of neocortical activity level and found that it was unchanged in both neuron types. Overall, the results of this thesis provide new insights into the functioning of microcircuits in vivo while confirming many findings from reduced preparations. In the future, it will be interesting to extend these initial in vivo measurements to other neuron and synapse types, particularly in awake animals engaged in different behavioral states.

EPFL2014

In vivo measurement of excitatory synaptic transmission between identified neurons in layer 2/3 mouse barrel cortex

Aurélie Pala

EPFL2014

EPFL2007