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Summary Electroencephalography (EEG)—the direct recording of the electrical activity of populations of neurons—is a tremendously important tool for diagnosing, treating, and researching epilepsy. Although standard procedures for recording and analyzing human EEG exist and are broadly accepted, there are no such standards for research in animal models of seizures and epilepsy—recording montages, acquisition systems, and processing algorithms may differ substantially among investigators and laboratories. The lack of standard procedures for acquiring and analyzing EEG from animal models of epilepsy hinders the interpretation of experimental results and reduces the ability of the scientific community to efficiently translate new experimental findings into clinical practice. Accordingly, the intention of this report is twofold: (1) to review current techniques for the collection and software-based analysis of neural field recordings in animal models of epilepsy, and (2) to offer pertinent standards and reporting guidelines for this research. Specifically, we review current techniques for signal acquisition, signal conditioning, signal processing, data storage, and data sharing, and include applicable recommendations to standardize collection and reporting. We close with a discussion of challenges and future opportunities, and include a supplemental report of currently available acquisition systems and analysis tools. This work represents a collaboration on behalf of the American Epilepsy Society/International League Against Epilepsy (AES/ILAE) Translational Task Force (TASK1-Workgroup 5), and is part of a larger effort to harmonize video-EEG interpretation and analysis methods across studies using in vivo and in vitro seizure and epilepsy models.

Summary Electroencephalography (EEG) is commonly used in epilepsy and neuroscience research to study brain activity. The principles of EEG recording such as signal acquisition, digitization, and conditioning share similarities between animal and clinical EEG systems. In contrast, preclinical EEG studies demonstrate more variability and diversity than clinical studies in the types and locations of EEG electrodes, methods of data analysis, and scoring of EEG patterns and associated behaviors. The TASK3 EEG working group of the International League Against Epilepsy/American Epilepsy Society (ILAE/AES) Joint Translational Task Force has developed a set of preclinical common data elements (CDEs) and case report forms (CRFs) for recording, analysis, and scoring of animal EEG studies. This companion document accompanies the first set of proposed preclinical EEG CRFs and is intended to clarify the CDEs included in these worksheets. We provide 7 CRF and accompanying CDE modules for use by the research community, covering video acquisition, electrode information, experimental scheduling, and scoring of EEG activity. For ease of use, all data elements and input ranges are defined in supporting Excel charts (Appendix S1).

INTRODUCTION—THE ALBIN AND DELONG MODELModern understanding of the basal ganglia (BG) dates to the Albin and DeLongmodel, which proposed a functional relationship between the nuclei of the BG[striatum, pallidum, substantia nigra, and subthalamic nucleus (STN)] (1,2). Inthis model, the BG controls the initiation and execution of motor programsthrough the interplay of the direct and indirect projection pathways, both ofwhich originate in the striatum (Fig. 1A). According to the model, activation F1of the direct pathway results in inhibition of pallidal output and consequentdisinhibition of thalamocortical projection neurons. Activation of the indirectpathway results in excitation of the internal segment of the globus pallidus

Drug-induced malfunction of nucleus accumbens (NAc) neurons underlies a key pathophysiology of drug addiction. Drug-induced changes in intrinsic membrane excitability of NAc neurons are thought to be critical for producing behavioral alterations. Previous studies demonstrate that, after short-term (2 d) or long-term (21 d) withdrawal from noncontingent cocaine injection, the intrinsic membrane excitability of NAc shell (NAcSh) neurons is decreased, and decreased membrane excitability of NAcSh neurons increases the acute locomotor response to cocaine. However, animals exhibit distinct cellular and behavioral alterations at different stages of cocaine exposure, suggesting that the decreased membrane excitability of NAc neurons may not be a persistent change. Here, we demonstrate that the membrane excitability of NAcSh neurons is differentially regulated depending on whether cocaine is administered contingently or noncontingently. Specifically, the membrane excitability of NAcSh medium spiny neurons (MSNs) was decreased at 2 d after withdrawal from either 5 d intraperitoneal injections (15 mg/kg) or cocaine self-administration (SA). At 21 d of withdrawal, the membrane excitability of NAcSh MSNs, which remained low in intraperitoneally pretreated rats, returned to a normal level in SA-pretreated rats. Furthermore, after a reexposure to cocaine after long-term withdrawal, the membrane excitability of NAcSh MSNs instantly returned to a normal level in intraperitoneally pretreated rats. Conversely, in SA-pretreated rats, the reexposure elevated the membrane excitability of NAcSh MSMs beyond the normal level. These results suggest that the dynamic alterations in membrane excitability of NAcSh MSNs, together with the dynamic changes in synaptic input, contribute differentially to the behavioral consequences of contingent and noncontingent cocaine administration.

Dopaminergic modulation produces a variety of functional changes in the principal cell of the striatum, the medium spiny neuron (MSN). Using a 189-compartment computational model of a ventral striatal MSN, we simulated whole cell D1- and D2-receptor–mediated modulation of both intrinsic (sodium, calcium, and potassium) and synaptic currents (AMPA and NMDA). Dopamine (DA) modulations in the model were based on a review of published experiments in both ventral and dorsal striatum. To objectively assess the net effects of DA modulation, we combined reported individual channel modulations into either D1- or D2-receptor modulation conditions and studied them separately. Contrary to previous suggestions, we found that D1 modulation had no effect on MSN nonlinearity and could not induce bistability. In agreement with previous suggestions, we found that dopaminergic modulation leads to changes in input filtering and neuronal excitability. Importantly, the changes in neuronal excitability agree with the classical model of basal ganglia function. We also found that DA modulation can alter the integration time window of the MSN. Interestingly, the effects of DA modulation of synaptic properties opposed the effects of DA modulation of intrinsic properties, with the synaptic modulations generally dominating the net effect. We interpret this lack of synergy to suggest that the regulation of whole cell integrative properties is not the primary functional purpose of DA. We suggest that D1 modulation might instead primarily regulate calcium influx to dendritic spines through NMDA and L-type calcium channels, by both direct and indirect mechanisms.

We describe a computational model of the principal cell in the nucleus accumbens (NAcb), the medium spiny projection (MSP) neuron. The model neuron, constructed in NEURON, includes all of the known ionic currents in these cells and receives synaptic input from simulated spike trains via NMDA, AMPA, and GABAAreceptors. After tuning the model by adjusting maximal current conductances in each compartment, the model cell closely matched whole-cell recordings from an adult rat NAcb slice preparation. Synaptic inputs in the range of 1000-1300 Hz are required to maintain an “up” state in the model. Cell firing in the model required concurrent depolarization of several dendritic branches, which responded independently to afferent input. Depolarization from action potentials traveled to the tips of the dendritic branches and increased Ca2+influx through voltage-gated Ca2+channels. As NMDA/AMPA current ratios were increased, the membrane showed an increase in hysteresis of “up” and “down” state dwell times, but intrinsic bistability was not observed. The number of oscillatory inputs required to entrain the model cell was determined to be ∼20% of the “up” state inputs. Altering the NMDA/AMPA ratio had a profound effect on processing of afferent input, including the ability to entrain to oscillations in afferent input in the theta range (4-12 Hz). These results suggest that afferent information integration by the NAcb MSP cell may be compromised by pathology in which the NMDA current is altered or modulated, as has been proposed in both schizophrenia and addiction.

Summary Axially excited chiral sculptured thin films (STFs) are shown to exhibit the circular Bragg phenomenon in the pre-resonant (long-wavelength) regime but not in some parts of the post-resonant (short-wavelength) regime. Chiral STFs act as very good polarization-independent reflectors in the vicinity of material resonances in the latter regime.

Stable brain function relies on homeostatic maintenance of the functional output of individual neurons. In general, neurons function by converting synaptic input to output as action potential firing. To determine homeostatic mechanisms that balance this input–output/synapse–membrane interaction, we focused on nucleus accumbens (NAc) neurons and demonstrated a novel form of synapse-to-membrane homeostatic regulation, homeostatic synapse-driven membrane plasticity (hSMP). ThroughhSMP, NAc neurons adjusted their membrane excitability to functionally compensate for basal shifts in excitatory synaptic input. Furthermore,hSMP was triggered by synaptic NMDA receptors (NMDARs) and expressed by the modification of SK-type Ca2+-activated potassium channels. Moreover,hSMP in NAc neurons was abolished in rats during a short- (2 d) or long- (21 d) term withdrawal from repeated intraperitoneal injections of cocaine (15 mg/kg/d, 5 d). These results suggest thathSMP is a novel form of synapse-to-membrane homeostatic plasticity and dysregulation ofhSMP may contribute to cocaine-induced cellular alterations in the NAc.

Utilizing a highly detailed model of the medium spiny neuron and a small network of these cells, in this chapter we analyze the processing of synaptic inputs by the striatum and the modulation of this processing via D1 and D2 activation. Computational models such as the one presented here allow for an examination of the cell or network’s response of an identical set of inputs under various sets of intrinsic and synaptic modulations. In the single cell model, D1 modulation leads to an increase in the output of the cell at all input frequencies, whereas D2 modulation led to a significant reduction at all of the synaptic input frequencies. These results are generally supportive of the ideas of the Albin-DeLong model, which originally suggested that there is segregation of the indirect and direct pathways in the dorsal striatum, and that D1 is excitatory and D2 is inhibitory. What has previously not been fully appreciated is the contribution and interaction of the synaptic modulations and the intrinsic modulations via DA to elicit this effect. Our model indicates that changes in the NMDA:AMPA ratio during pathological states may have an impact on normal synaptic input processing, and that lateral inhibition may have a greater effect at the network level than assumed from recent in vitro results. Elucidation of the role of dopaminergic modulation on network level interactions will play a crucial role in our understanding of information processing in the striatum.

The striatum includes the structures of the caudate, putamen, and nucleus accumbens (Nacb) and is a subset of the subcortical interconnected nuclei that make up the basal ganglia [39]. The striatum is one of the major input structures of the basal ganglia and integrates input from many cortical areas as well as the thalamus. In general, the dorsal striatum processes more input from the motor regions of the cortex, while the ventral striatum processes input predominantly from the limbic and cognitive areas of the brain [2]. The predominant cell in the striatum is the GABAergic medium spiny neuron (MSN), comprising over 95% of the striatal cells in the rodent [39]. The other 3 5% of cells in the striatum are GABAergic and cholinergic interneurons, each of which plays an important role in striatal function [38]. While each MSP cell has a small soma (10–15 mM), it has a large dendritic structure (200–300 mM) with numerous spines, and a branching axonal segment. The branching axonal arbor can be larger than the dendritic arbor, makes lateral contacts with other MSNs, and has one portion of the axonal segment projecting to efferent structures. The processing of afferent input by these MSNs has been the focus of numerous investigations, as has the role of dopaminergic (DA) modulation in affecting the integration of both inputs and the output of the MSNs [6, 32, 27, 31]. MSNs have a bimodal membrane potential under anesthesia or in vitro (see below), and one of the critical questions about their processing of cortical input has been whether they can maintain their depolarized state via intrinsic mechanisms without any further synaptic input. We have addressed some of the issues associated with cortical input to the striatal MSNs by examining how much synaptic input is required to keep the cell in the depolarized state, as well as comparing the structure of the cortical input

The neurobiological mechanisms by which high-frequency stimulation of the subthalamic nucleus (STN–HFS) alleviates the motor symptoms of Parkinson's disease (PD) remain unclear. In this study, we analyzed the effects of STN–HFS on motor behavior in intact or hemiparkinsonian rats (6-hydroxydopamine lesion of the substantia nigra pars compacta) and investigated the correlation between these effects and extracellular glutamate (Glu) and GABA levels, assessed by intracerebral microdialysis in the substantia nigra pars reticulata (SNr). STN–HFS at an intensity corresponding to the threshold inducing contralateral forelimb dyskinesia, increased Glu levels in the SNr of both intact and hemiparkinsonian rats. In contrast, STN–HFS at half this intensity did not affect Glu levels in the SNr in intact or hemiparkinsonian rats but increased GABA levels in hemiparkinsonian rats only. STN–HFS-induced forelimb dyskinesia was blocked by microinjection of the Glu receptor antagonist kynurenate into the SNr and facilitated by microinjection of a mixture of the Glu receptor agonists AMPA and NMDA into the SNr. These new neurochemical data suggest that STN–HFS-induced forelimb dyskinesia is mediated by glutamate, probably via the direct activation of STN axons, shedding light on the mechanisms of STN–HFS in PD.

Background: An understanding of the relationships between the anterior commissure-posterior commissure line (AC-PC), the subthalamic nucleus (STN), and red nucleus (RN) is imperative if these structures are to be used for targeting in deep brain stimulation. Currently, these relationships are incompletely understood and difficult to assess using conventional MRI. We examined the location and relationships of the STN and the RN to the AC-PC line and to each other in order to provide a greater understanding of their utility when targeting the STN, and the consistency of these anatomic relationships when examined using conventional MRI. Methods: A total of 52 STN and RN in 26 patients with Parkinson’s disease were evaluated on T2-weighted MR images. The anterior and posterior commissures and the border coordinates of the STN and RN were derived using frame coordinates. The distances from the midcommissural point (mcp) to the centers of the STN and RN, the diameters for each nucleus, and the distances between the nuclei were calculated in the x-, y-, and z-axes. Results: The mean AC-PC length was 26.1 ± 1.3 mm. The distance from the mcp to the center of the STN was 10 ± 0.7 mm in the x-axis, 0.2 ± 0.7 mm in the y-axis, and 3.3 ± 0.9 mm in the z-axis. The distance from the mcp to the center of the RN was 4.7 ± 0.6 mm in the x-axis, –5.9 ± 1.0 mm in the y-axis, and 6.1 ± 1.3 mm in the z-axis. The distance between the STN and RN was 2.3 ± 0.7 mm in the x-axis, 2.1 ± 1.0 mm in the y-axis, and –0.2 ± 1.3 mm in the z-axis. Conclusions: Although recent studies imply that the RN can be used as a relatively consistent marker for the position of the STN, the present data suggest otherwise. These data indicate that a single targeting method may be inadequate given the resolution of conventional MRI, and that it is imperative to use multiple anatomical measurements when targeting the STN for deep brain stimulation in Parkinson’s disease.

We describe a Markov chain representation for the summed asynchronous neural discharge currents of neurons grown on an electrode surface. We show that the spectrum of the recorded current signal can be used to characterize the type of neuron on the electrode.

OBJECTIVE: Microelectrode recording during deep brain stimulation surgery improves the likelihood of successful target localization and enables the electrophysiological characterization of human neural structures. Many clinical recording systems do not support the ability to capture research-quality recordings. Established clinical centers already using such equipment may be prevented from acquiring human intracranial data because of the need to completely change recording systems to obtain research-quality recordings. This technical note describes the novel design and implementation of a recording system that significantly improves research capabilities without disrupting the existing clinical setup. METHODS: This design introduces a second recording system (including pre-amplifier, differential amplifier, analog-to-digital converter, and computer with analysis software) that divides the microelectrode signal into two independent streams. RESULTS: This design preserves the existing intraoperative recording setup, but significantly improves research-level recording, data storage, and analysis capabilities. CONCLUSION: We provide the first description of such a system using components that are all commercially available and relatively inexpensive. This approach presents an appealing alternative to the purchase of an entirely new system for surgical teams that already perform intraoperative recordings to assist in stereotactic target localization, yet wish to expand their neurophysiological recording capabilities.