scholarly journals Implantable microcoils for intracortical magnetic stimulation

2016 ◽  
Vol 2 (12) ◽  
pp. e1600889 ◽  
Author(s):  
Seung Woo Lee ◽  
Florian Fallegger ◽  
Bernard D. F. Casse ◽  
Shelley I. Fried
Keyword(s):  
Cortical Neurons ◽  
Magnetic Stimulation ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Behavioral Responses ◽  
Wide Range ◽  
Cortical Pyramidal Neurons ◽  
Over Time

Neural prostheses that stimulate the neocortex have the potential to treat a wide range of neurological disorders. However, the efficacy of electrode-based implants remains limited, with persistent challenges that include an inability to create precise patterns of neural activity as well as difficulties in maintaining response consistency over time. These problems arise from fundamental limitations of electrodes as well as their susceptibility to implantation and have proven difficult to overcome. Magnetic stimulation can address many of these limitations, but coils small enough to be implanted into the cortex were not thought strong enough to activate neurons. We describe a new microcoil design and demonstrate its effectiveness for both activating cortical neurons and driving behavioral responses. The stimulation of cortical pyramidal neurons in brain slices in vitro was reliable and could be confined to spatially narrow regions (<60 μm). The spatially asymmetric fields arising from the coil helped to avoid the simultaneous activation of passing axons. In vivo implantation was safe and resulted in consistent and predictable behavioral responses. The high permeability of magnetic fields to biological substances may yield another important advantage because it suggests that encapsulation and other adverse effects of implantation will not diminish coil performance over time, as happens to electrodes. These findings suggest that a coil-based implant might be a useful alternative to existing electrode-based devices. The enhanced selectivity of microcoil-based magnetic stimulation will be especially useful for visual prostheses as well as for many brain-computer interface applications that require precise activation of the cortex.

Impact of Spontaneous Synaptic Activity on the Resting Properties of Cat Neocortical Pyramidal Neurons In Vivo

1998 ◽  
Vol 79 (3) ◽  
pp. 1450-1460 ◽  
Author(s):  
Denis Paré ◽  
Eric Shink ◽  
Hélène Gaudreau ◽  
Alain Destexhe ◽  
Eric J. Lang
Keyword(s):  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Synaptic Activity ◽  
Intact Brain ◽  
Lower Temperature ◽  
The Impact ◽  
Neocortical Pyramidal Neurons

Paré, Denis, Eric Shink, Hélène Gaudreau, Alain Destexhe, and Eric J. Lang. Impact of spontaneous synaptic activity on the resting properties of cat neocortical pyramidal neurons in vivo. J. Neurophysiol. 79: 1450–1460, 1998. The frequency of spontaneous synaptic events in vitro is probably lower than in vivo because of the reduced synaptic connectivity present in cortical slices and the lower temperature used during in vitro experiments. Because this reduction in background synaptic activity could modify the integrative properties of cortical neurons, we compared the impact of spontaneous synaptic events on the resting properties of intracellularly recorded pyramidal neurons in vivo and in vitro by blocking synaptic transmission with tetrodotoxin (TTX). The amount of synaptic activity was much lower in brain slices (at 34°C), as the standard deviation of the intracellular signal was 10–17 times lower in vitro than in vivo. Input resistances ( R ins) measured in vivo during relatively quiescent epochs (“control R ins”) could be reduced by up to 70% during periods of intense spontaneous activity. Further, the control R ins were increased by ∼30–70% after TTX application in vivo, approaching in vitro values. In contrast, TTX produced negligible R in changes in vitro (∼4%). These results indicate that, compared with the in vitro situation, the background synaptic activity present in intact networks dramatically reduces the electrical compactness of cortical neurons and modifies their integrative properties. The impact of the spontaneous synaptic bombardment should be taken into account when extrapolating in vitro findings to the intact brain.

Possible Effects of Depolarizing GABAA Conductance on the Neuronal Input–Output Relationship: A Modeling Study

2005 ◽  
Vol 93 (6) ◽  
pp. 3504-3523 ◽  
Author(s):  
Kenji Morita ◽  
Kunichika Tsumoto ◽  
Kazuyuki Aihara
Keyword(s):  
Firing Rate ◽  
Cortical Neurons ◽  
Reversal Potential ◽  
Pyramidal Cells ◽  
Resting Potential ◽  
Input Output ◽  
Wide Range ◽  
The Relationship

Recent in vitro experiments revealed that the GABAA reversal potential is about 10 mV higher than the resting potential in mature mammalian neocortical pyramidal cells; thus GABAergic inputs could have facilitatory, rather than inhibitory, effects on action potential generation under certain conditions. However, how the relationship between excitatory input conductances and the output firing rate is modulated by such depolarizing GABAergic inputs under in vivo circumstances has not yet been understood. We examine herewith the input–output relationship in a simple conductance-based model of cortical neurons with the depolarized GABAA reversal potential, and show that a tonic depolarizing GABAergic conductance up to a certain amount does not change the relationship between a tonic glutamatergic driving conductance and the output firing rate, whereas a higher GABAergic conductance prevents spike generation. When the tonic glutamatergic and GABAergic conductances are replaced by in vivo–like highly fluctuating inputs, on the other hand, the effect of depolarizing GABAergic inputs on the input–output relationship critically depends on the degree of coincidence between glutamatergic input events and GABAergic ones. Although a wide range of depolarizing GABAergic inputs hardly changes the firing rate of a neuron driven by noncoincident glutamatergic inputs, a certain range of these inputs considerably decreases the firing rate if a large number of driving glutamatergic inputs are coincident with them. These results raise the possibility that the depolarized GABAA reversal potential is not a paradoxical mystery, but is instead a sophisticated device for discriminative firing rate modulation.

scholarly journals Defective Dendrite Elongation but Normal Fertility in Mice Lacking the Rho-Like GTPase Activator Dbl

2002 ◽  
Vol 22 (9) ◽  
pp. 3140-3148 ◽  
Author(s):  
Emilio Hirsch ◽  
Michela Pozzato ◽  
Alessandro Vercelli ◽  
Laura Barberis ◽  
Ornella Azzolino ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Embryonic Stem ◽  
Large Family ◽  
Small Gtpases ◽  
Normal Morphology ◽  
Targeted Deletion ◽  
Cortical Pyramidal Neurons ◽  
Rho Family

ABSTRACT Dbl is the prototype of a large family of GDP-GTP exchange factors for small GTPases of the Rho family. In vitro, Dbl is known to activate Rho and Cdc42 and to induce a transformed phenotype. Dbl is specifically expressed in brain and gonads, but its in vivo functions are largely unknown. To assess its role in neurogenesis and gametogenesis, targeted deletion of the murine Dbl gene was accomplished in embryonic stem cells. Dbl-null mice are viable and did not show either decreased reproductive performances or obvious neurological defects. Histological analysis of mutant testis showed normal morphology and unaltered proliferation and survival of spermatogonia. Dbl-null brains indicated a correct disposition of the major neural structures. Analysis of cortical stratification indicated that Dbl is not crucial for neuronal migration. However, in distinct populations of Dbl-null cortical pyramidal neurons, the length of dendrites was significantly reduced, suggesting a role for Dbl in dendrite elongation.

scholarly journals Selective corticostriatal plasticity during acquisition of an auditory discrimination task

2014 ◽  
Author(s):  
Qiaojie Xiong ◽  
Petr Znamenskiy ◽  
Anthony Zador
Keyword(s):  
Cortical Neurons ◽  
Brain Slices ◽  
Frequency Discrimination ◽  
Auditory Discrimination ◽  
Low Frequencies ◽  
Reward Contingencies ◽  
Corticostriatal Plasticity

Perceptual decisions are based on the activity of sensory cortical neurons, but how organisms learn to transform this activity into appropriate actions remains unknown. Projections from the auditory cortex to the auditory striatum carry information that drives decisions in an auditory frequency discrimination task1. To assess the role of these projections in learning, we developed a Channelrhodopsin-2-based assay to selectively probe for synaptic plasticity associated with corticostriatal neurons representing different frequencies. Here we report that learning this auditory discrimination preferentially potentiates corticostriatal synapses from neurons representing either high or low frequencies, depending on reward contingencies. We observed frequency-dependent corticostriatal potentiation in vivo over the course of training, and in vitro in striatal brain slices. Our findings suggest a model in which selective potentiation of inputs representing different components of a sensory stimulus enables the learned transformation of sensory input into actions.

Activation of Serotonin Receptors Modulates Synaptic Transmission in Rat Cerebral Cortex

1999 ◽  
Vol 82 (6) ◽  
pp. 2989-2999 ◽  
Author(s):  
Fu-Ming Zhou ◽  
John J. Hablitz
Keyword(s):  
Cerebral Cortex ◽  
Pyramidal Neurons ◽  
Short Pulse ◽  
Inhibitory Neurons ◽  
Cellular Mechanisms ◽  
Postsynaptic Currents ◽  
Cortical Pyramidal Neurons ◽  
Immunohistochemical Studies

The cerebral cortex receives an extensive serotonergic (5-hydroxytryptamine, 5-HT) input. Immunohistochemical studies suggest that inhibitory neurons are the main target of 5-HT innervation. In vivo extracellular recordings have shown that 5-HT generally inhibited cortical pyramidal neurons, whereas in vitro studies have shown an excitatory action. To determine the cellular mechanisms underlying the diverse actions of 5-HT in the cortex, we examined its effects on cortical inhibitory interneurons and pyramidal neurons. We found that 5-HT, through activation of 5-HT2A receptors, induced a massive enhancement of spontaneous inhibitory postsynaptic currents (sIPSCs) in pyramidal neurons, lasting for ∼6 min. In interneurons, this 5-HT-induced enhancement of sIPSCs was much weaker. Activation of 5-HT2Areceptors also increased spontaneous excitatory postsynaptic currents (sEPSCs) in pyramidal neurons. This response desensitized less and at a slower rate. In contrast, 5-HT slightly decreased evoked IPSCs (eIPSCs) and eEPSCs. In addition, 5-HT via 5-HT3 receptors evoked a large and rapidly desensitizing inward current in a subset of interneurons and induced a transient enhancement of sIPSCs. Our results suggest that 5-HT has widespread effects on both interneurons and pyramidal neurons and that a short pulse of 5-HT is likely to induce inhibition whereas the prolonged presence of 5-HT may result in excitation.

Suppression of Ih Contributes to Propofol-Induced Inhibition of Mouse Cortical Pyramidal Neurons

2005 ◽  
Vol 94 (6) ◽  
pp. 3872-3883 ◽  
Author(s):  
Xiangdong Chen ◽  
Shaofang Shu ◽  
Douglas A. Bayliss
Keyword(s):  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Current Amplitude ◽  
Hcn Channels ◽  
General Anesthetic ◽  
Large Shift ◽  
Fast Kinetics ◽  
Membrane Hyperpolarization ◽  
Cortical Pyramidal Neurons

The contributions of the hyperpolarization-activated current, Ih, to generation of rhythmic activities are well described for various central neurons, particularly in thalamocortical circuits. In the present study, we investigated effects of a general anesthetic, propofol, on native Ih in neurons of thalamus and cortex and on the corresponding cloned HCN channel subunits. Whole cell voltage-clamp recordings from mouse brain slices identified neuronal Ih currents with fast activation kinetics in neocortical pyramidal neurons and with slower kinetics in thalamocortical relay cells. Propofol inhibited the fast-activating Ih in cortical neurons at a clinically relevant concentration (5 μM); inhibition of Ih involved a hyperpolarizing shift in half-activation voltage (Δ V1/2 approximately −9 mV) and a decrease in maximal available current (∼36% inhibition, measured at −120 mV). With the slower form of Ih expressed in thalamocortical neurons, propofol had no effect on current activation or amplitude. In heterologous expression systems, 5 μM propofol caused a large shift in V1/2 and decrease in current amplitude in homomeric HCN1 and linked heteromeric HCN1–HCN2 channels, both of which activate with fast kinetics but did not affect V1/2 or current amplitude of slowly activating homomeric HCN2 channels. With GABAA and glycine receptor channels blocked, propofol caused membrane hyperpolarization and suppressed action potential discharge in cortical neurons; these effects were occluded by the Ih blocker, ZD-7288. In summary, these data indicate that propofol selectively inhibits HCN channels containing HCN1 subunits, such as those that mediate Ih in cortical pyramidal neurons—and they suggest that anesthetic actions of propofol may involve inhibition of cortical neurons and perhaps other HCN1-expressing cells.

scholarly journals A fluorescent sensor for spatiotemporally resolved endocannabinoid dynamics in vitro and in vivo

2020 ◽  
Author(s):  
Ao Dong ◽  
Kaikai He ◽  
Barna Dudok ◽  
Jordan S Farrell ◽  
Wuqiang Guan ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Basolateral Amygdala ◽  
Fluorescent Sensor ◽  
Brain Slices ◽  
High Specificity ◽  
Cultured Neurons ◽  
Spatiotemporal Resolution ◽  
Wide Range

Endocannabinoids (eCBs) are retrograde neuromodulators that play an important role in a wide range of physiological processes; however, the release and in vivo dynamics of eCBs remain largely unknown, due in part to a lack of suitable probes capable of detecting eCBs with sufficient spatiotemporal resolution. Here, we developed a new eCB sensor called GRABeCB2.0. This genetically encoded sensor consists of the human CB1 cannabinoid receptor fused to circular-permutated EGFP, providing cell membrane trafficking, second-resolution kinetics, high specificity for eCBs, and a robust fluorescence response at physiological eCB concentrations. Using the GRABeCB2.0 sensor, we monitored evoked changes in eCB dynamics in both cultured neurons and acute brain slices. Interestingly, in cultured neurons we also observed spontaneous compartmental eCB transients that spanned a distance of approximately 11 μm, suggesting constrained, localized eCB signaling. Moreover, by expressing GRABeCB2.0 in the mouse brain, we readily observed foot shock-elicited and running-triggered eCB transients in the basolateral amygdala and hippocampus, respectively. Lastly, we used GRABeCB2.0 in a mouse seizure model and observed a spreading wave of eCB release that followed a Ca2+ wave through the hippocampus. Thus, GRABeCB2.0 is a robust new probe for measuring the dynamics of eCB release under both physiological and pathological conditions.

scholarly journals Excitatory GABA in Rodent Developing Neocortex In Vitro

2008 ◽  
Vol 100 (2) ◽  
pp. 609-619 ◽  
Author(s):  
Sylvain Rheims ◽  
Marat Minlebaev ◽  
Anton Ivanov ◽  
Alfonso Represa ◽  
Rustem Khazipov ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Reversal Potential ◽  
Pyramidal Cells ◽  
Oscillatory Activity ◽  
Resting Membrane Potential ◽  
Network Oscillations ◽  
Excitatory Gaba

GABA depolarizes immature cortical neurons. However, whether GABA excites immature neocortical neurons and drives network oscillations as in other brain structures remains controversial. Excitatory actions of GABA depend on three fundamental parameters: the resting membrane potential ( Em), reversal potential of GABA ( EGABA), and threshold of action potential generation ( Vthr). We have shown recently that conventional invasive recording techniques provide an erroneous estimation of these parameters in immature neurons. In this study, we used noninvasive single N-methyl-d-aspartate and GABA channel recordings in rodent brain slices to measure both Em and EGABA in the same neuron. We show that GABA strongly depolarizes pyramidal neurons and interneurons in both deep and superficial layers of the immature neocortex (P2–P10). However, GABA generates action potentials in layer 5/6 (L5/6) but not L2/3 pyramidal cells, since L5/6 pyramidal cells have more depolarized resting potentials and more hyperpolarized Vthr. The excitatory GABA transiently drives oscillations generated by L5/6 pyramidal cells and interneurons during development (P5–P12). The NKCC1 co-transporter antagonist bumetanide strongly reduces [Cl−]i, GABA-induced depolarization, and network oscillations, confirming the importance of GABA signaling. Thus a strong GABA excitatory drive coupled with high intrinsic excitability of L5/6 pyramidal neurons and interneurons provide a powerful mechanism of synapse-driven oscillatory activity in the rodent neocortex in vitro. In the companion paper, we show that the excitatory GABA drives layer-specific seizures in the immature neocortex.

scholarly journals Impaired state-dependent potentiation of GABAergic synaptic currents triggers seizures in an idiopathic generalized epilepsy model

2020 ◽  
Author(s):  
Chun-Qing Zhang ◽  
Mackenzie A. Catron ◽  
Li Ding ◽  
Caitlyn M. Hanna ◽  
Martin J. Gallagher ◽  
...  
Keyword(s):  
Slow Wave ◽  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Slow Wave Sleep ◽  
Ex Vivo ◽  
Brain Slices ◽  
Idiopathic Generalized Epilepsy ◽  
Synaptic Currents ◽  
Generalized Epilepsy

AbstractIdiopathic generalized epilepsy(IGE) patients have genetic causes and their seizure onset mechanisms particularly during sleep remain elusive. Here we proposed that sleep-like slow-wave oscillations(0.5 Hz SWOs) potentiated excitatory or inhibitory synaptic currents in layer V cortical pyramidal neurons from wild-type(wt) mouse ex vivo brain slices. In contrast, SWOs potentiated excitatory, not inhibitory, currents in cortical neurons from heterozygous(het) knock-in(KI) IGE mice(GABAA receptor γ2 subunit Gabrg2Q390X mutation), creating an imbalance between evoked excitatory and inhibitory currents to effectively prompt neuronal action potentials. Similarly, more physiologically similar up/down-state(present during slow-wave sleep) induction in cortical neurons could potentiate excitatory synaptic currents within slices from wt/het Gabrg2Q390X KI mice. Consequently, SWOs or up/down-state induction in vivo (using optogenetic method) could trigger epileptic spike-wave discharges(SWDs) in het Gabrg2Q390X KI mice. To our knowledge, this is the first operative mechanism to explain why epileptic SWDs preferentially happen during non-REM sleep or quiet-wakefulness in human IGE patients.

scholarly journals Intracellular Properties of Deep-Layer Pyramidal Neurons in Frontal Eye Field of Macaque Monkeys

2021 ◽  
Vol 13 ◽  
Author(s):  
Charlotte Piette ◽  
Marie Vandecasteele ◽  
Clémentine Bosch-Bouju ◽  
Valérie Goubard ◽  
Vincent Paillé ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Deep Layer ◽  
Brain Slices ◽  
Cell Types ◽  
Frontal Eye Field ◽  
Visual Responses ◽  
Biophysical Properties ◽  
Eye Field

Although many details remain unknown, several positive statements can be made about the laminar distribution of primate frontal eye field (FEF) neurons with different physiological properties. Most certainly, pyramidal neurons in the deep layer of FEF that project to the brainstem carry movement and fixation signals but clear evidence also support that at least some deep-layer pyramidal neurons projecting to the superior colliculus carry visual responses. Thus, deep-layer neurons in FEF are functionally heterogeneous. Despite the useful functional distinctions between neuronal responses in vivo, the underlying existence of distinct cell types remain uncertain, mostly due to methodological limitations of extracellular recordings in awake behaving primates. To substantiate the functionally defined cell types encountered in the deep layer of FEF, we measured the biophysical properties of pyramidal neurons recorded intracellularly in brain slices issued from macaque monkey biopsies. Here, we found that biophysical properties recorded in vitro permit us to distinguish two main subtypes of regular-spiking neurons, with, respectively, low-resistance and low excitability vs. high-resistance and strong excitability. These results provide useful constraints for cognitive models of visual attention and saccade production by indicating that at least two distinct populations of deep-layer neurons exist.

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