Neocortical LTD via Coincident Activation of Presynaptic NMDA and Cannabinoid Receptors

Sjöström, P. Jesper; Turrigiano, Gina G.; Nelson, Sacha B.

doi:10.1016/s0896-6273(03)00476-8

Cited by 535 publications

(789 citation statements)

References 81 publications

Supporting

Mentioning

717

Contrasting

Unclassified

Order By: Relevance

“…The role of endocannabinoids in cerebellar plasticity Endocannabinoid receptor-dependent forms of presynaptic LTD exist outside the cerebellum [10,17,35,40], and endocannabinoids are well-described in mediating shortterm plasticity in the cerebellum [6,7,22]. In contrast to the form of LTD described in this study, these CB1 The role of endocannabinoids in PF long-term plasticity had been less clear.…”

Section: Demonstration Of Preltdmentioning

confidence: 56%

Presynaptically expressed long-term depression at cerebellar parallel fiber synapses

Qiu

Knöpfel

2008

Pflugers Arch - Eur J Physiol

View full text Add to dashboard Cite

Plasticity at synapses between parallel fiber (PF) and Purkinje neurons (PN) is widely accepted as a cellular model for certain forms of cerebellar learning. Although PF-PN synapses are known to express bidirectional longterm plasticity at the postsynaptic site, long-term plasticity at the presynaptic site is currently limited to potentiation of the synapses. In this paper, we report on presynaptically expressed PF long-term depression (preLTD) that is observed when presynaptically expressed PF long-term potentiation (preLTP) is pharmacologically prevented. PF preLTD is most efficiently induced by 4 Hz PF stimulation and requires activation of cannabinoid CB1 receptors. Our results indicate that, during preLTD induction, endocannabinoids are released in an NMDA receptor-dependent, but not mGlu1 receptor-dependent, fashion. We conclude that bidirectional plasticity mechanisms exist for both presynaptic and postsynaptic components of cerebellar learning.

show abstract

Section: Demonstration Of Preltdmentioning

confidence: 56%

Presynaptically expressed long-term depression at cerebellar parallel fiber synapses

Qiu

Knöpfel

2008

Pflugers Arch - Eur J Physiol

View full text Add to dashboard Cite

show abstract

“…In view of the results on LTD in layer--V neocortical neurons 44 , this trace could be related to endocannabinoids released from the postsynaptic site. Coincidence of this slow trace with the activation of presynaptic NMDA receptors (which rapidly respond to the glutamate released by presynaptic activity x(t)) could be the trigger signal for LTD 44 . Indeed, the duration of the LTD part in the STDP function increases, if the endocannabinoid trace is artificially prolonged (see Fig 9 of 44 ).…”

Section: Discussionmentioning

confidence: 91%

“…Coincidence of this slow trace with the activation of presynaptic NMDA receptors (which rapidly respond to the glutamate released by presynaptic activity x(t)) could be the trigger signal for LTD 44 . Indeed, the duration of the LTD part in the STDP function increases, if the endocannabinoid trace is artificially prolonged (see Fig 9 of 44 ). In other neuron types and brain areas, the same mathematical model (but with different parameters) could correspond to different biophysical mechanisms of LTD. For example, in hippocampal CA1 neurons, the trace --could reflect the calcium entry through voltage--gated ion channels during depolarization which, when combined with synaptic signals (caused by the presynaptic spike arrival x), would give rise to calcium signals necessary to trigger LTD (reviewed in 19--20,44 ).…”

Section: Discussionmentioning

confidence: 99%

“…The trace could correspond to the amount of glutamate bound to the postsynaptic NMDA receptor but this is controversial 44 . A high momentary voltage u can be induced by a backpropagating action potential; interestingly, backpropagation of action potentials is more likely and more reliable to occur in the background of a weak depolarization of the dendrite 44 ----and such a weak depolarization potentially corresponds to the term + in our model.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Connectivity reflects coding: a model of voltage-based STDP with homeostasis

et al. 2010

View full text Add to dashboard Cite

Electrophysiological connectivity patterns in cortex often show a few strong connections, sometimes bidirectional, in a sea of weak connections. In order to explain these connectivity patterns, we use a model of Spike--Timing--Dependent Plasticity where synaptic changes depend on presynaptic spike arrival and the postsynaptic membrane potential, filtered with two different time constants. The model describes several nonlinear effects in STDP experiments, as well as the voltage dependence of plasticity. We show that in a simulated recurrent network of spiking neurons our plasticity rule leads not only to development of localized receptive fields, but also to connectivity patterns that reflect the neural code: for temporal coding paradigms with spatio--temporal input correlations, strong connections are predominantly unidirectional, whereas they are bidirectional under rate coded input with spatial correlations only. Thus variable connectivity patterns in the brain could reflect different coding principles across brain areas; moreover simulations suggest that plasticity is surprisingly fast.

show abstract

“…Experimental studies have demonstrated that the Calcium control hypothesis does not hold true for excitatory synapses between cortical pyramidal cells -at which there is no evidence for the existence of a triphasic STDP rule. A variety of alternative mechanisms, including metabotropic glutamate receptor, pre-synaptic NMDAr and retrograde endocannabinoid signalling, have been implicated in the induction of LTD by spike-timing stimulation protocols in cortex [77][78][79][80]. It seems likely that this dichotomy in synaptic plasticity mechanisms between cortex and hippocampus might both reflect and be reflected by functional differences in neural processing mediated by these regions.…”

Section: Discussionmentioning

confidence: 99%

Calcium control of triphasic hippocampal STDP

Bush¹,

Jin

2012

J Comput Neurosci

View full text Add to dashboard Cite

Synaptic plasticity is believed to represent the neural correlate of mammalian learning and memory function. It has been demonstrated that changes in synaptic conductance can be induced by approximately synchronous pairings of pre-and post-synaptic action potentials delivered at low frequencies. It has also been established that NMDAr-dependent Calcium influx into dendritic spines represents the critical signal for plasticity induction, and can account for this spike-timing dependent plasticity (STDP) as well as experimental data obtained using other stimulation protocols. However, subsequent empirical studies have delineated a more complex relationship between spike-timing, firing rate, stimulus duration and post-synaptic bursting in dictating changes in the conductance of hippocampal excitatory synapses. It has yet to be established whether the Calcium control hypothesis can account for this more recent data. Here, we present a detailed biophysical model of single dendritic spines on a CA1 pyramidal neuron, describe the NMDAr-dependent Calcium influx generated by different stimulation protocols, and present a parsimonious model of Calcium driven kinase and phosphotase dynamics that dictate transitions between binary synaptic weight states. We demonstrate the manner in which this model can account for various experimental observations of synaptic plasticity and be used to make predictions regarding the dynamics of depolarisation and NMDAr activation generated by STDP protocols as well as the synaptic weight change induced under other experimental conditions. We then discuss how this parsimonious, unified computational model of synaptic plasticity might be utilised to appraise the activity-dependent refinement of neural circuitry induced by more realistic firing patterns. IntroductionSynaptic plasticity -the process of activity dependent change in synaptic conductance -is widely believed to represent the neural correlate of mammalian learning and memory function [1][2][3]. Since the first experimental demonstrations of long-term potentiation (LTP) and depression (LTD), a wealth of empirical data regarding the induction, expression and maintenance of synaptic plasticity in different cortical regions has been obtained [4][5][6][7][8]. In spite of the heterogeneity of plasticity mechanisms observed throughout the brain, changes in the strength of excitatory synapses afferent on CA1 pyramidal neurons in the hippocampus represent the best studied form in the mammalian cortex [9][10][11][12]. At these synapses, Calcium influx into dendritic spines represents the critical signal for synaptic plasticity induction [13][14][15][16][17][18][19][20]. Large, transient elevations in intracellular [Ca 2+ ] generate LTP via the preferential activation of kinase pathways while modest, sustained elevations in intracellular [Ca 2+ ] generate LTD via the preferential activation of phosphotase pathways [21][22][23][24][25]. Initially, empirical observations of synaptic plasticity were mediated by tetanic stimulation protoc...

show abstract

Neocortical LTD via Coincident Activation of Presynaptic NMDA and Cannabinoid Receptors

Cited by 535 publications

References 81 publications

Presynaptically expressed long-term depression at cerebellar parallel fiber synapses

Presynaptically expressed long-term depression at cerebellar parallel fiber synapses

Connectivity reflects coding: a model of voltage-based STDP with homeostasis

Calcium control of triphasic hippocampal STDP

Contact Info

Product

Resources

About