Plasticity in the intrinsic excitability of cortical pyramidal neurons

Desai, Niraj S.; Rutherford, Lana C.; Turrigiano, Gina G.

doi:10.1038/9165

Cited by 794 publications

(820 citation statements)

References 41 publications

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“…Therefore, it is possible that SNA recovers after gabazine application through fast changes in cellular excitability and that compensatory changes in mPSC amplitude take longer to be expressed. Similar findings have been reported in activity-blocked cultured networks where changes in current densities of different voltage-gated channels increased the excitability of the neurons (46,47). The precise details of the compensatory responses underlying the homeostatic recovery of activity levels are not well understood, in part because studies have not directly compared the time course of activity recovery and changes in quantal amplitude.…”

Section: Discussionsupporting

confidence: 55%

“…After glutamatergic blockade, activity recovers in part because of a fast loading of intracellular chloride, which strengthens the unblocked GABAergic currents (22,44). After GABAergic block, there may be fast changes in the probability of release (45) and changes in cellular excitability (46,47). We have found that after GABA A block in ovo, there are fast changes (Յ12 h) in cellular excitability that begin to dissipate toward control levels after 48 h of GABA A block (J.C.W.…”

Section: Discussionmentioning

confidence: 99%

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GABA _A transmission is a critical step in the process of triggering homeostatic increases in quantal amplitude

Wilhelm

Wenner

2008

Proc. Natl. Acad. Sci. U.S.A.

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When activity levels are altered over days, a network of cells is capable of recognizing this perturbation and triggering several distinct compensatory changes that should help to recover and maintain the original activity levels homeostatically. One feature commonly observed after activity blockade has been a compensatory increase in excitatory quantal amplitude. The sensing machinery that detects altered activity levels is a central focus of the field currently, but thus far it has been elusive. The vast majority of studies that reduce network activity also reduce neurotransmission. We address the possibility that reduced neurotransmission can trigger increases in quantal amplitude. In this work, we blocked glutamatergic or GABAA transmission in ovo for 2 days while maintaining relatively normal network activity. We found that reducing GABAA transmission triggered compensatory increases in both GABA and AMPA quantal amplitude in embryonic spinal motoneurons. Glutamatergic blockade had no effect on quantal amplitude. Therefore, GABA binding to the GABAA receptor appears to be a critical step in the sensing machinery for homeostatic synaptic plasticity. The findings suggest that homeostatic increases in quantal amplitude may normally be triggered by reduced levels of activity, which are sensed in the developing spinal cord by GABA, via the GABA A receptor. Therefore, GABA appears to be serving as a proxy for activity levels.activity ͉ neurotransmitter receptor ͉ postsynaptic ͉ synaptic scaling ͉ synaptic plasticity S pontaneous network activity (SNA) is a prominent feature of developing neural networks that consists of episodic bursts of activity separated by periods of quiescence (1-3). SNA is produced by hyperexcitable, recurrently connected circuits in which glutamate and GABA are both excitatory early in development. In the spinal cord, SNA drives embryonic limb movements and is known to be important for various aspects of limb (4) and motoneuron development (5, 6). Reducing spontaneous network activity in the embryonic chick in vivo leads to compensatory increases in the strength of excitatory GABAergic and AMPAergic synapses (7). These compensatory increases in synaptic strength have been described in several systems where they appear to act in a manner to recover and maintain network activity levels homeostatically (homeostatic synaptic plasticity) (8, 9). Activity perturbations lead to several different forms of homeostatic synaptic plasticity, including changes in quantal amplitude, probability of release, and frequency of miniature postsynaptic currents (mPSCs). In the present work, we focus on compensatory changes in quantal (mPSC) amplitude. Changes in mPSC amplitude have been studied intensely in cultured networks where prolonged activity reduction results in an increase in the amplitude of excitatory mPSCs and a decrease in the amplitude of inhibitory mPSCs (10-12). Changes in mPSC amplitude are achieved through alterations in the number of postsynaptic receptors and/or the amount of transmitter re...

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

GABA _A transmission is a critical step in the process of triggering homeostatic increases in quantal amplitude

Wilhelm

Wenner

2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Given BDNF's established role in mediating processes related to learning and memory (Korte et al 1995, Patterson et al 1996, Desai et al 1999, this increased susceptibility to cognitive impairment suggests that the variation in BDNF may play a role in the development of neuropsychiatric disorders as well as affect nervous system functioning.…”

Section: Variant Bdnf Met and Behavioural Impairmentsmentioning

confidence: 99%

Impact of Genetic Variant BDNF (Val66Met) on Brain Structure and Function

Chen

Bath

McEwen

et al. 2008

Novartis Foundation Symposia

102

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A common single-nucleotide polymorphism in the human brain-derived neurotrophic factor (BDNF) gene, a methionine (Met) substitution for valine (Val) at codon 66 (Val66Met), is associated with alterations in brain anatomy and memory, but its relevance to clinical disorders is unclear. We generated a variant BDNF mouse (BDNF Met/Met ) that reproduces the phenotypic hallmarks in humans with the variant allele. Variant BDNF Met was expressed in brain at normal levels, but its secretion from neurons was defective. In this context, the BDNF Met/Met mouse represents a unique model that directly links altered activity-dependent release of BDNF to a defined set of in vivo consequences. Our subsequent analyses of these mice elucidated a phenotype that had not been established in human carriers: increased anxiety. When placed in conflict settings, BDNF Met/Met mice display increased anxiety-related behaviours that were not normalized by the antidepressant, fluoxetine. A genetic variant BDNF may thus play a key role in genetic predispositions to anxiety and depressive disorders.

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“…For the last 10 years, solutions were proposed for emulating classic learning rules in SNNs [24,30,4], by means of drastic simplifications that often resulted in losing precious features of firing time-based computing. As an alternative, various researchers have proposed different ways to exploit recent advances in neuroscience about synaptic plasticity [1], especially IP 2 [10,9] or STDP 3 [28,19], that is usually presented as the Hebb rule, revisited in the context of temporal coding. A current trend is to propose computational justifications for plasticity-based learning rules, in terms of entropy minimization [5] as well as log-likelihood [35] or mutual information maximization [8,46,7].…”

Section: Spiking Neuron Networkmentioning

confidence: 99%

Delay learning and polychronization for reservoir computing

Paugam-Moisy¹,

Martinez²,

Bengio³

2008

Neurocomputing

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We propose a multi-timescale learning rule for spiking neuron networks, in the line of the recently emerging field of reservoir computing. The reservoir is a network model of spiking neurons, with random topology and driven by STDP (spike-time-dependent plasticity), a temporal Hebbian unsupervised learning mode, biologically observed. The model is further driven by a supervised learning algorithm, based on a margin criterion, that affects the synaptic delays linking the network to the readout neurons, with classification as a goal task. The network processing and the resulting performance can be explained by the concept of polychronization, proposed by Izhikevich [Polychronization: computation with spikes, Neural Comput. 18(2) (2006) 245-282], on physiological grounds. The model emphasizes that polychronization can be used as a tool for exploiting the computational power of synaptic delays and for monitoring the topology and activity of a spiking neuron network. r

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Plasticity in the intrinsic excitability of cortical pyramidal neurons

Cited by 794 publications

References 41 publications

GABA _A transmission is a critical step in the process of triggering homeostatic increases in quantal amplitude

GABA _A transmission is a critical step in the process of triggering homeostatic increases in quantal amplitude

Impact of Genetic Variant BDNF (Val66Met) on Brain Structure and Function

Delay learning and polychronization for reservoir computing

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Plasticity in the intrinsic excitability of cortical pyramidal neurons

Cited by 794 publications

References 41 publications

GABA A transmission is a critical step in the process of triggering homeostatic increases in quantal amplitude

GABA A transmission is a critical step in the process of triggering homeostatic increases in quantal amplitude

Impact of Genetic Variant BDNF (Val66Met) on Brain Structure and Function

Delay learning and polychronization for reservoir computing

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Product

Resources

About

GABA _A transmission is a critical step in the process of triggering homeostatic increases in quantal amplitude

GABA _A transmission is a critical step in the process of triggering homeostatic increases in quantal amplitude