Generation Of Field Potentials Research Articles

A Minimal Biophysical Model of Neocortical Pyramidal Cells: Implications for Frontal Cortex Microcircuitry and Field Potential Generation.

Ca2+ spikes initiated in the distal trunk of layer 5 pyramidal cells (PCs) underlie nonlinear dynamic changes in the gain of cellular response, critical for top-down control of cortical processing. Detailed models with many compartments and dozens of ionic channels can account for this Ca2+ spike-dependent gain and associated critical frequency. However, current models do not account for all known Ca2+-dependent features. Previous attempts to include more features have required increasing complexity, limiting their interpretability and utility for studying large population dynamics. We overcome these limitations in a minimal two-compartment biophysical model. In our model, a basal-dendrites/somatic compartment included fast-inactivating Na+ and delayed-rectifier K+ conductances, while an apical-dendrites/trunk compartment included persistent Na+, hyperpolarization-activated cation (I h ), slow-inactivating K+, muscarinic K+, and Ca2+ L-type. The model replicated the Ca2+ spike morphology and its critical frequency plus three other defining features of layer 5 PC synaptic integration: linear frequency-current relationships, back-propagation-activated Ca2+ spike firing, and a shift in the critical frequency by blocking I h Simulating 1000 synchronized layer 5 PCs, we reproduced the current source density patterns evoked by Ca2+ spikes and describe resulting medial-frontal EEG on a male macaque monkey. We reproduced changes in the current source density when I h was blocked. Thus, a two-compartment model with five crucial ionic currents in the apical dendrites reproduces all features of these neurons. We discuss the utility of this minimal model to study the microcircuitry of agranular areas of the frontal lobe involved in cognitive control and responsible for event-related potentials, such as the error-related negativity.SIGNIFICANCE STATEMENT A minimal model of layer 5 pyramidal cells replicates all known features crucial for distal synaptic integration in these neurons. By redistributing voltage-gated and returning transmembrane currents in the model, we establish a theoretical framework for the investigation of cortical microcircuit contribution to intracranial local field potentials and EEG. This tractable model will enable biophysical evaluation of multiscale electrophysiological signatures and computational investigation of cortical processing.

Transcranial magnetic stimulation induced early silent period and rebound activity re-examined.

Despite being widely studied, the underlying mechanisms of transcranial magnetic brain stimulation (TMS) induced motor evoked potential (MEP), early cortical silent period (CSP) and rebound activity are not fully understood. Our aim is to better characterize these phenomena by combining various analysis tools on firing motor units. Responses of 29 tibialis anterior (TA) and 8 abductor pollicis brevis (APB) motor units to TMS pulses were studied using discharge rate and probability-based tools to illustrate the profile of the synaptic potentials as they develop on motoneurons in 24 healthy volunteers. According to probability-based methods, TMS pulse produces a short-latency MEP which is immediately followed by CSP that terminates at rebound activity. Discharge rate analysis, however, revealed not three, but just two events with distinct time courses; a long-lasting excitatory period (71.2 ± 9.0 ms for TA and 42.1 ± 11.2 ms for APB) and a long-latency inhibitory period with duration of 57.9 ± 9.5 ms for TA and 67.3 ± 13.8 ms for APB. We propose that part of the CSP may relate to the falling phase of net excitatory postsynaptic potential induced by TMS. Rebound activity, on the other hand, may represent tendon organ inhibition induced by MEP activated soleus contraction and/or long-latency intracortical inhibition. Due to generation of field potentials when high intensity TMS is used, this study is limited to investigate the events evoked by low intensity TMS only and does not provide information about later parts of much longer CSPs induced by high intensity TMS. Adding discharge rate analysis contributes to obtain a more accurate picture about the characteristics of TMS-induced events. These results have implications for interpreting motor responses following TMS for diagnosis and overseeing recovery from various neurological conditions.

Generation of field potentials and modulation of their dynamics through volume integration of cortical activity.

Field potentials (FPs) recorded within the brain, often called "local field potentials" (LFPs), are useful measures of net synaptic activity in a neuronal ensemble. However, due to volume conduction, FPs spread beyond regions of underlying synaptic activity, and thus an "LFP" signal may not accurately reflect the temporal patterns of synaptic activity in the immediately surrounding neuron population. To better understand the physiological processes reflected in FPs, we explored the relationship between the FP and its membrane current generators using current source density (CSD) analysis in conjunction with a volume conductor model. The model provides a quantitative description of the spatiotemporal summation of immediate local and more distant membrane currents to produce the FP. By applying the model to FPs in the macaque auditory cortex, we have investigated a critical issue that has broad implications for FP research. We have shown that FP responses in particular cortical layers are differentially susceptible to activity in other layers. Activity in the supragranular layers has the strongest contribution to FPs in other cortical layers, and infragranular FPs are most susceptible to contributions from other layers. To define the physiological processes generating FPs recorded in loci of relatively weak synaptic activity, strong effects produced by synaptic events in the vicinity have to be taken into account. While outlining limitations and caveats inherent to FP measurements, our results also suggest specific peak and frequency band components of FPs can be related to activity in specific cortical layers. These results may help improving the interpretability of FPs.

Lumbosacral sensory neuronal activity is enhanced by activation of urothelial purinergic receptors

Urothelial purinergic receptors are important for the regulation of afferent sensory pathways in bladder pain and overactivity. Using in vivo electrophysiological recordings we evaluated the activity of spinal dorsal horn neurons in female rats at the L6/S1 level when urinary bladder pressure was abruptly increased. Intravesical infusion of ATP and systemic application of suramin allowed us to evaluate the contribution of urothelial purinergic receptors. Rats were anesthetized with isofluorane. Suprapubic, venous and tracheal catheters were implanted. Laminectomy was performed at the L6–S1 spinal levels. The cervical spinal cord was transected, and rats were mechanically pithed. Anesthesia was stopped, rats were ventilated, and a muscle relaxant was administered. The frequency of spinal neural activity was recorded via tungsten electrodes inserted into the dorsal horn at the L6–S1 level. The signal was amplified, filtered and recorded with a data acquisition system at 10kHz sampling rate. Vital signs as well as bladder pressure were monitored in real time. We evaluated field potentials during intravesical pressure steps ranging from 0 to 60cm H2O in (A) control (saline in the bladder), (B) after stimulation of urothelial purinergic receptors (1mM vesical ATP), and (C) after the intravenous application of the non-specific purinergic antagonist suramin (100mg/kg). Pressure steps were maintained for 1min followed by 3min for recovery. Only neurons that showed an increased activity during bladder distention were evaluated. Under control conditions, the generation of field potentials increased concomitantly with bladder pressure steps, showing an activity change threshold between 20 and 40cm H2O. Intravesical application of 1mM ATP produced an increase in baseline activity, indicative of noxious stimulation, and spinal neuronal activity markedly increased above 40cm H2O pressure. Systemic suramin prevented the increase in neural activity in response to pressure changes, even after intravesical ATP. These results suggest that urothelial purinergic receptors are important modulators of lumbosacral dorsal spinal neuronal activity. The inhibitory effects of suramin imply that enhanced lumbosacral neuronal signals result from activation of C-fibers during noxious bladder stimulation.

Epileptiform EEG Spikes and Their Functional Significance

Field potentials detected in the space surrounding cellular elements of the nervous system are essential in the diagnosis of epileptic seizures. This article describes the elementary mechanisms underlying the generation of field potentials and the special functional conditions leading to epileptiform field potentials. Primary transmembranous currents generate secondary ional currents along the cell membranes in intra- and extracellular compartments. The portion of these currents that flows through the brain tissue to the cortical surface can be detected as field potentials. A high synchronization of these field potentials is needed to induce brain signals. Field potentials recorded during epileptic activity are based on alterations in neuronal membrane potentials. Paroxysmal depolarization shift has proved to be characteristic in the epileptiform activity of individual neurons. Epileptiform field potentials are generated in functionally different structures with different elementary mechanisms. In focal convulsive activity limited to the cortex, the surface potential does not necessarily reflect the bioelectrical events in deeper cortical laminae and can be interrupted in different ways. The discrepancy between superficial EEG potentials and neocortical output may be the basis for dissociation between EEG signals and clinical signs.

Laminar analysis of initiation and spread of epileptiform discharges in three in vitro models

Overexcitation of neuronal networks in some forebrain structures and pathological synchronization of neuronal activity play crucial role in epileptic seizures. Seizure activity can be elicited experimentally by different convulsants. Because of various distribution of excitatory and inhibitory connections in the neocortex there might be laminar differences in seizure sensitivity. Current source density (CSD) analysis or immunocytochemical c-Fos localization offer suitable tools to localize increased activation of neurons during seizure. In the present experiments, interictal epileptiform activity elicited by 4-aminopiridine, bicuculline or Mg 2+-free solution was recorded with a 16-channel multielectrode assembly in different layers of the somatosensory cortex, and CSDs were calculated. Parallel c-Fos immunocytochemistry was applied. Each convulsant elicited characteristic activation pattern. 4-Aminopiridine induced relatively short discharges, which were associated with a huge sink in layer V, the sink and source pattern was relatively simple. Mg 2+-free solution elicited the longest discharges, sinks appeared typically in the supragranular layers II and III than quickly distributed toward layers V and VI. Bicuculline induced rather similar seizure pattern as Mg 2+-free solution, but the amplitudes of field potentials were larger, while the durations shorter. The peak of c-Fos activation, however, was not parallel with the largest electrical activation. Larger amount of stained cells appeared in layers II and III in 4-aminopiridine and bicuculline, respectively. In Mg 2+-free solution the highest c-Fos activity was detected in upper layer VI. Long-lasting cellular effects do not always correspond to the largest electrical responses, which are primarily determined by the activation of asymmetrical pyramidal neurons. Interneurons, which possess more symmetric process arborisation, play less important role in the generation of field potentials, although they may be intensively activated during seizure.

Genetic Inactivation of an Inwardly Rectifying Potassium Channel (Kir4.1 Subunit) in Mice: Phenotypic Impact in Retina

The inwardly rectifying potassium channel Kir4.1 has been suggested to underlie the principal K(+) conductance of mammalian Müller cells and to participate in the generation of field potentials and regulation of extracellular K(+) in the retina. To further assess the role of Kir4.1 in the retina, we generated a mouse line with targeted disruption of the Kir4.1 gene (Kir4.1 -/-). Müller cells from Kir4.1 -/- mice were not labeled with an anti-Kir4.1 antibody, although they appeared morphologically normal when stained with an anti-glutamine synthetase antibody. In contrast, in Müller cells from wild-type littermate (Kir4.1 +/+) mice, Kir4.1 was present and localized to the proximal endfeet and perivascular processes. In situ whole-cell patch-clamp recordings showed a 10-fold increase in the input resistance and a large depolarization of Kir4.1 -/- Müller cells compared with Kir4.1 +/+ cells. The slow PIII response of the light-evoked electroretinogram (ERG), which is generated by K(+) fluxes through Müller cells, was totally absent in retinas from Kir4.1 -/- mice. The b-wave of the ERG, in contrast, was spared in the null mice. Overall, these results indicate that Kir4.1 is the principal K(+) channel subunit expressed in mouse Müller glial cells. The highly regulated localization and the functional properties of Kir4.1 in Müller cells suggest the involvement of this channel in the regulation of extracellular K(+) in the mouse retina.

Generation of field potentials in the brain.

Neuronal function is closely correlated with bioelectrical signals. These electrical events can be detected as field potentials in the space surrounding cellular elements of the nervous system. The basic mechanisms underlying the generation of field potentials are described.

Self-Regulation of the Brain and Behavior

I: Neurophysiological Mechanisms That Regulate Brain Potential Changes.- 1 Neuronal Mechanisms Underyling the Generation of Field Potentials.- 2 Electrogenesis of Slow Potentials of the Brain.- 3 Central Gating Mechanisms That Regulate Event-Related Potentials and Behavior.- II: Self-Regulation of EEG Frequency Bands and Its Application to the Treatment of Human Epilepsy.- Section A: EEG Frequency Bands.- 4 Classification and Overview of CNS Electrical Activity Tested on Operant Conditioning.- 5 Focused Arousal, 40-Hz EEG, and Dysfunction.- Section B: EEG Biofeedback in the Treatment of Epilepsy.- 6 Operant Conditioning of Single Neurons in Monkeys and Its Theoretical Application to EEG Operant Conditioning in Human Epilepsy.- 7 The Role of Sensorimotor Rhythmic EEG Activity in the Etiology and Treatment of Generalized Motor Seizures.- 8 Applications of Operant Conditioning of the EEG for the Management of Epileptic Seizures.- 9 Biofeedback Control in Epilepsy and Neuroses.- III: Operant Control of Event-Related and Slow Potentials of the Brain.- Introduction: Event-Related Brain Potentials.- The Editors.- Section A: Self-Regulation of Evoked Potentials.- 10 Biofeedback of Very Early Potentials from the Brain Stem.- 11 Operantly Controlled Somatosensory Brain Potentials: Specific Effects on Pain Processes.- 12 Operant Control of Evoked Potentials: Some Comments on the Learning Characteristics in Man and on the Conditioning of Subcortical Responses in the Curarized Rat.- Section B: Meaning and Regulation of Slow Brain Potentials.- 13 Performance Enhancements with Cortical Negative Slow Potential Shifts in Monkey and Human.- 14 Regulation of Slow Brain Potentials Affects Task Performance.- 15 Operant Control of Slow Brain Potentials: A Tool in the Investigation of the Potential's Meaning and Its Relation to Attentional Dysfunction.- IV: Theoretical Considerations and Models.- The Editors.- Section A: Subjective Experience and the Activation of CNS Activity.- 16 On the Relationships Among Subjective Experience, Behavior, and Physiological Activity in Biofeedback Learning.- 17 Dead Souls: Or Why the Neurobehavioral Science of Emotion Should Pay Attention to Cognitive Science.- 18 Goal-Directed Behavior and Self-Regulation in the Organism.- Section B: The Operant Approach and the Concept of Control in the Self-Regulation of the Brain.- 19 Concepts of Control in Biofeedback.- 20 Operant Mechanisms in Physiological Regulation.- References.- Author Index.