Direct Cortical Inputs Erase Long-Term Potentiation at Schaffer Collateral Synapses

Izumi, Yukitoshi; Zorumski, Charles F.

doi:10.1523/jneurosci.3346-08.2008

Cited by 35 publications

(51 citation statements)

References 46 publications

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“…In addition, anodal DC stimulation applied over the rat sensorimotor cortex has been shown to modify adenosine-elicited accumulation of cAMP (4), inducing increases in protein kinase C and calcium levels (5, 6). Moreover, the involvement of adenosine A1 receptors in the LTD of cortical circuits has been reported recently (24,49). Here we show that local microinjection of the adenosine A1 receptor antagonist DPCPX prevents the LTD evoked in the somatosensory cortex after cathodal tDCS.…”

Section: Discussionsupporting

confidence: 67%

“…Based on previous studies of the molecular processes underlying LTD (24,25), we investigated the effect of the selective A1 adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) when injected at the cortical recording site. Local microinjection of DPCPX significantly diminished the LTD induced after cathodal tDCS compared with vehicle controls (n = 3; P < 0.001, oneway ANOVA) (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Transcranial direct-current stimulation modulates synaptic mechanisms involved in associative learning in behaving rabbits

Márquez-Ruiz

Leal‐Campanario

Sánchez-Campusano

et al. 2012

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

179

152

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Transcranial direct-current stimulation (tDCS) is a noninvasive brain stimulation technique that has been successfully applied for modulation of cortical excitability. tDCS is capable of inducing changes in neuronal membrane potentials in a polarity-dependent manner. When tDCS is of sufficient length, synaptically driven aftereffects are induced. The mechanisms underlying these after-effects are largely unknown, and there is a compelling need for animal models to test the immediate effects and after-effects induced by tDCS in different cortical areas and evaluate the implications in complex cerebral processes. Here we show in behaving rabbits that tDCS applied over the somatosensory cortex modulates cortical processes consequent to localized stimulation of the whisker pad or of the corresponding area of the ventroposterior medial (VPM) thalamic nucleus. With longer stimulation periods, poststimulation effects were observed in the somatosensory cortex only after cathodal tDCS. Consistent with the polarity-specific effects, the acquisition of classical eyeblink conditioning was potentiated or depressed by the simultaneous application of anodal or cathodal tDCS, respectively, when stimulation of the whisker pad was used as conditioned stimulus, suggesting that tDCS modulates the sensory perception process necessary for associative learning. We also studied the putative mechanisms underlying immediate effects and after-effects of tDCS observed in the somatosensory cortex. Results when pairs of pulses applied to the thalamic VPM nucleus (mediating sensory input) during anodal and cathodal tDCS suggest that tDCS modifies thalamocortical synapses at presynaptic sites. Finally, we show that blocking the activation of adenosine A1 receptors prevents the long-term depression (LTD) evoked in the somatosensory cortex after cathodal tDCS.T he effects of weak direct-current (DC) stimulation on the excitability of the central nervous system were reported decades ago. Invasive stimulation in acute animals demonstrated that intracortical or epidural application of weak DC induces polarityspecific changes in the neuronal excitability of motor (1, 2), visual (1), and somatosensory (3) cortices. Interestingly, these changes persist for several minutes after the DC stimulus offset (3), sharing some molecular mechanisms with the classical long-term plasticity. In this regard, it has been demonstrated that anodal DC stimulation applied on the rat sensorimotor cortex modifies adenosine-elicited accumulation of cAMP (4), inducing an increase of protein kinase C and calcium levels (5, 6). tDCS has been successfully applied for modulation of cortical excitability in humans (7-11), and interest is growing in the use of this technique as a noninvasive tool for basic and clinical research in various neurologic pathologies, including chronic pain, stroke, and depression (12-15). Little is known about the molecular and/or cellular mechanisms underlying the neuromodulatory after-effects of tDCS, however. For this reason, new experimental models...

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Section: Discussionsupporting

confidence: 67%

Section: Resultsmentioning

confidence: 99%

Transcranial direct-current stimulation modulates synaptic mechanisms involved in associative learning in behaving rabbits

Márquez-Ruiz

Leal‐Campanario

Sánchez-Campusano

et al. 2012

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

179

152

View full text Add to dashboard Cite

show abstract

“…One confounding aspect is feedforward inhibition that accompanies CA3 and EC excitatory inputs in vivo and in slice preparations. EC activation can have a largely inhibitory effect on CA3 inputs to SR, leading to LTD of these CA3 inputs (Izumi & Zorumski, 2008;Pissidaki & Poirazi, 2007;Remondes & Schuman, 2002). If inhibition is blocked, LTP in SLM and SR synapses can result due to activation of the opposite pathway.…”

Section: Cooperation Across Synaptic Layersmentioning

confidence: 99%

Spine Head Calcium as a Measure of Summed Postsynaptic Activity for Driving Synaptic Plasticity

2014

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We use a computational model of a hippocampal CA1 pyramidal cell to demonstrate that spine head calcium provides an instantaneous readout at each synapse of the postsynaptic weighted sum of all presynaptic activity impinging on the cell. The form of the readout is equivalent to the functions of weighted, summed inputs used in neural network learning rules. Within a dendritic layer, peak spine head calcium levels are either a linear or sigmoidal function of the number of coactive synapses, with nonlinearity depending on the ability of voltage spread in the dendrites to reach calcium spike threshold. This is strongly controlled by the potassium A-type current, with calcium spikes and the consequent sigmoidal increase in peak spine head calcium present only when the A-channel density is low. Other membrane characteristics influence the gain of the relationship between peak calcium and the number of active synapses. In particular, increasing spine neck resistance increases the gain due to increased voltage responses to synaptic input in spine heads. Colocation of stimulated synapses on a single dendritic branch also increases the gain of the response. Input pathways cooperate: CA3 inputs to the proximal apical dendrites can strongly amplify peak calcium levels due to weak EC input to the distal dendrites, but not so strongly vice versa. CA3 inputs to the basal dendrites can boost calcium levels in the proximal apical dendrites, but the relative electrical compactness of the basal dendrites results in the reverse effect being less significant. These results give pointers as to how to better describe the contributions of pre-and Spine Head Calcium Driving Synaptic Plasticity 2195 postsynaptic activity in the learning "rules" that apply in these cells. The calcium signal is closer in form to the activity measures used in traditional neural network learning rules than to the spike times used in spike-timing-dependent plasticity.

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“…[2,58,59]), both homosynaptic and heterosynaptic (e.g. [60,61]). For that reason, there are several previous manipulations of different proteins that resulted in an enhanced LTP coupled to decreased performance in memory-related tasks (e.g.…”

Section: Possible Relevance Of the Effects Of Caffeine On Ltp For Memmentioning

confidence: 99%

Caffeine, Adenosine Receptors, and Synaptic Plasticity

Costenla

Cunha

Mendonça

2010

JAD

112

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Abstract. Few studies to date have looked at the effects of caffeine on synaptic plasticity, and those that did used very high concentrations of caffeine, whereas the brain concentrations attained by regular coffee consumption in humans should be in the low micromolar range, where caffeine exerts pharmacological actions mainly by antagonizing adenosine receptors. Accordingly, rats drinking caffeine (1 g/L) for 3 weeks, displayed a concentration of caffeine of circa 22 µM in the hippocampus. It is known that selective adenosine A1 receptor antagonists facilitate, whereas selective adenosine A2A receptor antagonists attenuate, long term potentiation (LTP) in the hippocampus. Although caffeine is a non-selective antagonist of adenosine receptors, it attenuates frequency-induced LTP in hippocampal slices in a manner similar to selective adenosine A2A receptor antagonists. These effects of low micromolar concentration of caffeine (30 µM) are maintained in aged animals, which is important when a possible beneficial effect for caffeine in age-related cognitive decline is proposed. Future studies will still be required to confirm and detail the involvement of A1 and A2A receptors in the effects of caffeine on hippocampal synaptic plasticity, using both pharmacological and genetic approaches.

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Direct Cortical Inputs Erase Long-Term Potentiation at Schaffer Collateral Synapses

Cited by 35 publications

References 46 publications

Transcranial direct-current stimulation modulates synaptic mechanisms involved in associative learning in behaving rabbits

Transcranial direct-current stimulation modulates synaptic mechanisms involved in associative learning in behaving rabbits

Spine Head Calcium as a Measure of Summed Postsynaptic Activity for Driving Synaptic Plasticity

Caffeine, Adenosine Receptors, and Synaptic Plasticity

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