Microstimulation of the somatosensory cortex can substitute for vibrissa stimulation during Pavlovian conditioning

Leal‐Campanario, Rocío; Delgado‐García, José M.; Gruart, Agnès

doi:10.1073/pnas.0603584103

Cited by 39 publications

(40 citation statements)

References 35 publications

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“…A previous study indicated that specific areas of the somatosensory cortex are activated during this type of associative learning, depending on the skin site of the CS presentation (17). As in that study, we used a train of pulses (100 ms, 200 Hz) presented to the whisker pad as CS, followed 250 ms later by an air puff presented to the ipsilateral cornea as an unconditioned stimulus (US).…”

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.

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179

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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: 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.

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179

152

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“…Thereby, beyond the local encoding of stimulus features, learning plays an important role, as by learning, meaning is attributed to the electrical stimuli (Scheich and Breindl, 2002;Bradley et al, 2005;Fernández et al, 2005;Leal-Campanario et al, 2006). When animals learn to discriminate or categorize natural, e.g., visual, auditory, or somatosensory stimuli, large-scale stimulus-specific patterns emerge from the ongoing activity of sensory cortex as has been demonstrated by recording electrocorticograms (ECoGs) at high spatial resolution (Barrie et al, 1996;Freeman, 2000;Ohl et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…In animal models it has been shown that electrically evoked percepts vary in accordance with the location of the stimulation site within retinotopic (Bradley et al, 2005), tonotopic (Scheich and Breindl, 2002;Otto et al, 2005), and somatotopic (Leal-Campanario et al, 2006;Fitzsimmons et al, 2007) map representations. Several studies have specifically demonstrated that psychophysical properties of electrically evoked percepts can be linked to the representational topographies of cortical maps at the stimulation site (Romo et al, 2000;Bartlett et al, 2005), in some cases even to tuning properties of small sets of directly excited neurons located within one or a few cortical columns (Tehovnik et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Auditory Cortical Activity after Intracortical Microstimulation and Its Role for Sensory Processing and Learning

Deliano¹,

Scheich²,

Ohl³

2009

J. Neurosci.

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Several studies have shown that animals can learn to make specific use of intracortical microstimulation (ICMS) of sensory cortex within behavioral tasks. Here, we investigate how the focal, artificial activation by ICMS leads to a meaningful, behaviorally interpretable signal. In natural learning, this involves large-scale activity patterns in widespread brain-networks. We therefore trained gerbils to discriminate closely neighboring ICMS sites within primary auditory cortex producing evoked responses largely overlapping in space. In parallel, during training, we recorded electrocorticograms (ECoGs) at high spatial resolution. Applying a multivariate classification procedure, we identified late spatial patterns that emerged with discrimination learning from the ongoing poststimulus ECoG. These patterns contained information about the preceding conditioned stimulus, and were associated with a subsequent correct behavioral response by the animal. Thereby, relevant pattern information was mainly carried by neuron populations outside the range of the lateral spatial spread of ICMS-evoked cortical activation (ϳ1.2 mm). This demonstrates that the stimulated cortical area not only encoded information about the stimulation sites by its focal, stimulus-driven activation, but also provided meaningful signals in its ongoing activity related to the interpretation of ICMS learned by the animal. This involved the stimulated area as a whole, and apparently required large-scale integration in the brain. However, ICMS locally interfered with the ongoing cortical dynamics by suppressing pattern formation near the stimulation sites. The interaction between ICMS and ongoing cortical activity has several implications for the design of ICMS protocols and cortical neuroprostheses, since the meaningful interpretation of ICMS depends on this interaction.

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“…Electrical microstimulation can establish causal links between the activity of groups of neurons and perceptual and cognitive functions [1][2][3][4][5][6] . However, the number and identities of neurons microstimulated, as well as the number of action potentials evoked, are difficult to ascertain 7,8 .…”

Section: Introductionmentioning

confidence: 99%

Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice

Huber

Petreanu

Ghitani

et al. 2008

Nature

491

397

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Electrical microstimulation can establish causal links between the activity of groups of neurons and perceptual and cognitive functions [1][2][3][4][5][6] . However, the number and identities of neurons microstimulated, as well as the number of action potentials evoked, are difficult to ascertain 7,8 . To address these issues we introduced the light-gated algal channel channelrhodopsin-2 (ChR2) 9 specifically into a small fraction of layer 2/3 neurons of the mouse primary somatosensory cortex. ChR2 photostimulation in vivo reliably generated stimulus-locked action potentials 10-13 at frequencies up to 50 Hz. Naïve mice readily learned to detect brief trains of action potentials (5 light pulses, 1ms, 20 Hz). After training, mice could detect a photostimulus firing a single action potential in approximately 300 neurons. Even fewer neurons (approximately 60) were required for longer stimuli (5 action potentials, 250 ms). Our results show that perceptual decisions and learning can be driven by extremely brief epochs of cortical activity in a sparse subset of supragranular cortical pyramidal neurons.We used in utero electroporation 14 to introduce ChR2 fused to a green fluorescent protein (ChR2-GFP 15 ) together with a red fluorescent cytosolic marker 15 (RFP) into neocortical pyramidal neurons (Fig. 1a, Methods). In the adult brain ChR2-GFP expression was restricted to pyramidal cells in layers 2/3 (> 99.4 %), mainly in the barrel cortex (Fig 1a, 2a). In vivo two-photon imaging and retrospective immunohistology revealed that ChR2-GFP was localized to the neuronal plasma membrane. ChR2-GFP was expressed in about half (48.9 ± 5.3 %, n = 10, 5 mice; see Methods) of red fluorescent layer 2/3 neurons (Supplementary Movie 1). ChR2-GFP invaded the soma, dendrites, and axons (Fig. 1b, 1c). ChR2-GFP expression was stable for at least 8 months and did not seem to perturb neuronal morphology (Fig. 1a-c, Methods).We next characterized the responses of ChR2-GFP-expressing neurons to photostimulation in anesthetized mice. To sample from the entire population of ChR2-GFP-expressing neurons, unbiased by ChR2-GFP expression level, we recorded from red fluorescent neurons using two-photon targeted loose-patch recordings 16 (Fig. 1c, d). Photostimuli consisted of light pulses, produced by a blue miniature light emitting diode (LED; 470 nm), centered on the recording window (Fig. 1d). At maximum light intensities (I max = 11.6 mW/mm 2 at the surface of the brain, centered on the diode; 1-10 ms duration) about half (51 %) of the patched red neurons (n = 39/77, 8 mice) responded reliably to single photostimuli with at AUTOR CONTRIBUTIONS DH and KS designed the experiments. DH performed the behavioral and in vivo physiological experiments. LP, DH and KS performed the brain slice measurements. NG performed histology. SR, TH, ZM, KS provided advice and equipment. DH and KS wrote the paper. All authors discussed the results and commented on the manuscript.

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Microstimulation of the somatosensory cortex can substitute for vibrissa stimulation during Pavlovian conditioning

Cited by 39 publications

References 35 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

Auditory Cortical Activity after Intracortical Microstimulation and Its Role for Sensory Processing and Learning

Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice

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