Coincident pre‐ and postsynaptic activity downregulates NKCC1 to hyperpolarize E<sub>Cl</sub> during development

Balena, Trevor; Woodin, Melanie A.

doi:10.1111/j.1460-9568.2008.06194.x

Cited by 46 publications

(50 citation statements)

References 57 publications

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“…This effect was not due to changes in intrinsic membrane properties of tagged cells or modifications in E GPSP , since similar firing properties and E GPSP values were observed before and after pairing. Unlike the present experiments, in cultured hippocampal neurons bearing depolarizing responses to GABA, repetitive postsynaptic spiking within Ϯ 5 ms of GABA Amediated synaptic transmission was able to downregulate the expression of the cation-chloride cotransporter NKCC1 leading to a reduction in [Cl Ϫ ] i and a shift of E Cl below V R (Balena and Woodin, 2008). It should be stressed, however, that while in our experiments the STDP protocol consisted in 10 pairs of single postsynaptic spikes with unitary GPSPs, cultured neurons were stimulated with 150 pairs of presynaptic and postsynaptic spikes at 5 Hz.…”

Section: Discussioncontrasting

confidence: 44%

At Immature Mossy-Fiber–CA3 Synapses, Correlated Presynaptic and Postsynaptic Activity Persistently Enhances GABA Release and Network Excitability via BDNF and cAMP-Dependent PKA

Sivakumaran¹,

Mohajerani²,

Cherubini³

2009

J. Neurosci.

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In the adult rat hippocampus, the axons of granule cells in the dentate gyrus, the mossy fibers (MF), form excitatory glutamatergic synapses with CA3 principal cells. In neonates, MF release into their targets mainly GABA, which at this developmental stage is depolarizing. Here we tested the hypothesis that, at immature MF-CA3 synapses, correlated presynaptic [single fiber-evoked GABA A -mediated postsynaptic potentials (GPSPs)] and postsynaptic activity (back propagating action potentials) may exert a critical control on synaptic efficacy. This form of plasticity, called spike-timing-dependent plasticity (STDP), is a Hebbian type form of learning extensively studied at the level of glutamatergic synapses. Depending on the relative timing, pairing postsynaptic spiking and single MF-GPSPs induced bidirectional changes in synaptic efficacy. In case of positive pairing, spike-timing-dependent-long-term potentiation (STD-LTP) was associated with a persistent increase in GPSP slope and in the probability of cell firing. The transduction pathway involved a rise of calcium in the postsynaptic cell and the combined activity of cAMP-dependent PKA (protein kinase A) and brain-derived neurotrophic factor (BDNF). Retrograde signaling via BDNF and presynaptic TrkB receptors led to a persistent increase in GABA release. In "presynaptically" silent neurons, the enhanced probability of GABA release induced by the pairing protocol, unsilenced these synapses. Shifting E GABA from the depolarizing to the hyperpolarizing direction with bumetanide failed to modify synaptic strength. Thus, STD-LTP of GPSPs provides a reliable way to convey information from granule cells to the CA3 associative network at a time when glutamatergic synapses are still poorly developed.

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Section: Discussioncontrasting

confidence: 44%

At Immature Mossy-Fiber–CA3 Synapses, Correlated Presynaptic and Postsynaptic Activity Persistently Enhances GABA Release and Network Excitability via BDNF and cAMP-Dependent PKA

Sivakumaran¹,

Mohajerani²,

Cherubini³

2009

J. Neurosci.

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“…Recent experimental results (21)(22)(23)(24)(25)(26) show that inhibitory synapses can be modified by coincident pre-and postsynaptic activity with a coincidence time window ∆t. Additionally, sole presynaptic spikes lead to a reduction of synaptic efficacy.…”

Section: Inhibitory Synaptic Plasticitymentioning

confidence: 99%

“…To mimic glutamatergic and GABAergic transmission, the synapses were conductance-based with reversal potentials V E = 0 mV and V I = −80 mV and time constants τ E = 5 ms, and τ I = 10 ms for excitation and inhibition respectively (see Methods). In our simulations, the strength of the inhibitory synapses was initially weak but could change due to a spike timing dependent plasticity rule, in which near coincident pre-and postsynaptic action potentials induce potentiation of the synapse (21)(22)(23)(24)(25)(26). In addition to this Hebbian term of the learning rule, every presynaptic spike leads to synaptic depression (21,22) ( Fig.…”

mentioning

confidence: 99%

Inhibitory Plasticity Balances Excitation and Inhibition in Sensory Pathways and Memory Networks

Vogels

Sprekeler

Zenke

et al. 2011

Science

712

1,046

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."A Hebbian form of synaptic plasticity at inhibitory synapses generates balanced input currents and sparse neuronal responses that stabilize memory traces in neuronal networks" Cortical neurons receive balanced excitatory and inhibitory membrane currents.Here, we show that such a balance can be established and maintained in an experiencedependent manner by synaptic plasticity at inhibitory synapses. The mechanism we put forward provides an explanation for the sparse firing patterns observed in response to natural stimuli and fits well with a recently observed interaction of excitatory and inhibitory receptive field plasticity. We show that the introduction of inhibitory plasticity in suitable recurrent networks provides a homeostatic mechanism that leads to asynchronous irregular network states. Further, it can accommodate synaptic memories with activity patterns that become indiscernible from the background state, but can be re-activated by external stimuli. Our results suggest an essential role of inhibitory plasticity in the formation and maintenance of functional cortical circuitry. 1The balance of excitatory and inhibitory membrane currents a neuron experiences during stimulated and ongoing activity has been the topic of many recent studies (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). This balance, first defined as equal average amounts of de-and hyperpolarizing membrane currents (from hereon referred to as "global balance") is thought to be essential for maintaining stability of cortical networks (1, 2). In the balanced state networks display asynchronous irregular (AI) dynamics that mimic activity patterns observed in cortical neurons. Such asynchronous network states facilitate rapid responses to small changes in the input (2-4), providing an ideal substrate for cortical signal processing (5,15,16). Pathologies that disrupt the balance of excitation and inhibition have often been implicated in neurological diseases such as epilepsy or schizophrenia (17, 18).Moreover, the input currents to a given cortical neuron are not merely globally balanced. Excitatory and inhibitory inputs are coupled also in time (6-8) and co-tuned for different stimulus features (9,10). The tight coupling of excitation and inhibition suggests a more precise, detailed balance, in which each excitatory input arrives at the cell together with an inhibitory counterpart, supposedly supplied through feedforward inhibition (Fig. 1 A). These observations fit well with models of cortical processing in which balanced sensory inputs are left unattended, but can be transiently (11), or persistently turned on by targeted disruptions of the balance (12-14).Although it is widely thought that the excitatory-inhibitory balance plays an important role for stability and information processing in cortical networks, it is still not understood by which mechanisms this balance is established and maintained in the presence of ongoing sensory experiences. Inspired by recent experimental results (9), we investigate the hypothesis that synaptic plastic...

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“…Since NKCC1 is expressed at the AIS, changes in E GABA at the ChC synapse may occur naturally as a function of the spike output of the postsynaptic neuron, with high levels of activity leading to a depolarizing shift in E GABA and increasing neuronal excitability. In the second study, near-coincident firing of presynaptic and postsynaptic cells caused a hyperpolarizing shift in E GABA via NKCC1 alterations (Balena and Woodin, 2008), effectively increasing the strength of inhibition and decreasing excitability. Thus, mechanisms exist to bidirectionally shift E GABA viachanges in NKCC1 activity, and may explain the large variability we observe in our gramicidin recordings.…”

Section: Discussionmentioning

confidence: 98%

State-Dependent Function of Neocortical Chandelier Cells

Woodruff¹,

McGarry²,

Vogels³

et al. 2011

J. Neurosci.

120

118

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Chandelier (axoaxonic) cells (ChCs) are a distinct group of GABAergic interneurons that innervate the axon initial segments of pyramidal cells. However, their circuit role and the function of their clearly defined anatomical specificity remain unclear. Recent work has demonstrated that chandelier cells can produce depolarizing GABAergic PSPs, occasionally driving postsynaptic targets to spike. On the other hand, other work suggests that ChCs are hyperpolarizing and may have an inhibitory role. These disparate functional effects may reflect heterogeneity among ChCs. Here, using brain slices from transgenic mouse strains, we first demonstrate that, across different neocortical areas and genetic backgrounds, upper Layer 2/3 ChCs belong to a single electrophysiologically and morphologically defined population, extensively sampling Layer 1 inputs with asymmetric dendrites. Consistent with being a single cell type, we find electrical coupling between ChCs. We then investigate the effect of chandelier cell activation on pyramidal neuron spiking in several conditions, ranging from the resting membrane potential to stimuli designed to approximate in vivo membrane potential dynamics. We find that under quiescent conditions, chandelier cells are capable of both promoting and inhibiting spike generation, depending on the postsynaptic membrane potential. However, during in vivo-like membrane potential fluctuations, the dominant postsynaptic effect was a strong inhibition. Thus, neocortical chandelier cells, even from within a homogeneous population, appear to play a dual role in the circuit, helping to activate quiescent pyramidal neurons, while at the same time inhibiting active ones.

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Coincident pre‐ and postsynaptic activity downregulates NKCC1 to hyperpolarize E_Cl during development

Cited by 46 publications

References 57 publications

At Immature Mossy-Fiber–CA3 Synapses, Correlated Presynaptic and Postsynaptic Activity Persistently Enhances GABA Release and Network Excitability via BDNF and cAMP-Dependent PKA

At Immature Mossy-Fiber–CA3 Synapses, Correlated Presynaptic and Postsynaptic Activity Persistently Enhances GABA Release and Network Excitability via BDNF and cAMP-Dependent PKA

Inhibitory Plasticity Balances Excitation and Inhibition in Sensory Pathways and Memory Networks

State-Dependent Function of Neocortical Chandelier Cells

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Coincident pre‐ and postsynaptic activity downregulates NKCC1 to hyperpolarize ECl during development

Cited by 46 publications

References 57 publications

At Immature Mossy-Fiber–CA3 Synapses, Correlated Presynaptic and Postsynaptic Activity Persistently Enhances GABA Release and Network Excitability via BDNF and cAMP-Dependent PKA

At Immature Mossy-Fiber–CA3 Synapses, Correlated Presynaptic and Postsynaptic Activity Persistently Enhances GABA Release and Network Excitability via BDNF and cAMP-Dependent PKA

Inhibitory Plasticity Balances Excitation and Inhibition in Sensory Pathways and Memory Networks

State-Dependent Function of Neocortical Chandelier Cells

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Product

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Coincident pre‐ and postsynaptic activity downregulates NKCC1 to hyperpolarize E_Cl during development