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Extracellular potential recorded in the brain typically reflects activity of multiple cells and processes happening in multiple spatial and temporal scales, depending on the type of electrode and geometric relation between the setups and the tissue. While easy to record, it is notoriously difficult to interpret due to the long range of the electric field. When multiple recordings are available it is possible to estimate the local distribution of current sources (CSD analysis). Our recent method, kernel Current Source Density, allows to estimate CSD from arbitrary distribution of contacts, however, when the number of contacts is large conecptual and computational problems make the CSD analysis difficult. Discuss the challenges appearing in CSD analysis of multielectrode recordings in complex setups. Reproducible kernel Hilbert spaces, singular value decomposition, Python. A wavelet-style multiscale approach to the CSD analysis leads to optimal use of high density probes. For data coming from single cells, morphological information allows one to obtain estimates of CSD distribution along the cell morphology. It is possible to combine recordings of different type, such as ECoG and SEEG, to improve localization of specific phenomena. Kernel CSD analysis and its variants may significantly improve understanding and interpretation of extracellularly recorded brain activity. FINANCIAL SUPPORT: This work was supported by the Polish Ministry for Science and Higher Education grant 2948/7.PR/2013/2 and Narodowe Centrum Nauki grant 2015/17/B/ST7/04123.
BACKGROUND AND AIMS: Develop a novel method to assist presurgical evaluation in epileptic patients with pharmacologically intractable epileptic seizures, by spatial source localization of epileptic epicenters using stereoencephalography (SEEG) and electrocorticography (EcoG) recordings. METHODS: We developed kernel Electrical Source Imaging (kESI), which takes into account realistic brain morphology and spatial variations in brain conductivity. This method is parameter free, can localize multiple sources, and is flexible to allow arbitrary electrode positions. To account for the patient specific brain morphology, a patient’s MR scan can be used to evaluate the measured potential in a forward model using Finite Element Method in FEniCS software. The inhomogeneous electrical conductivity of the gray and white matter, skin and skull etc. can also be included. kESI is an inverse method, which relies on the construction of kernel functions requiring computation of the potentials generated in the brain by numerous basis functions covering the probed volume. This approach is based on our previous approach of kernel Current Source Density in 3 dimensions, while utilizing the patient specific forward modeling scheme above. RESULTS: To show the proof-of-concept we generated dipolar ground truth data in a simplified spherical brain model with uniform conductivity. We assumed the electrodes on the surface of the sphere and inside the spherical volume emulating ECoG and SEEG style recordings respectively. We show that the proposed method works, and can help in deciding how different distributions of electrodes affect the quality of reconstruction. CONCLUSIONS: kESI method facilitates accurate localization of the seizure onset zones, and a possible procedure for prescribing optimal distributions of electrodes depending on available prior knowledge (e.g. dysfunction of specific brain structures) and clinical resources (availability of specific electrodes, etc.).
INTRODUCTION: Ketamine, at subanesthetic doses, produces psychotomimetic effects. In rodents, ketamine produces characteristic changes in oscillatory activity that can be recorded in local field potentials (LFP). One effect after systemic injection of ketamine is the emergence of abnormal high frequency oscillations (HFO) 130 ‑180 Hz that have been described in many rodent brain areas. Recently, we have shown that the olfactory bulb (OB) plays an important role in the generation of HFO after ketamine. AIM(S): The aim of the present study was to examine the extent to which nasal respiration may drive abnormal HFO after ketamine, in freely‑moving rats. METHOD(S): LFPs (from the OB) and nasal respiration (thermocouples implanted in the nares) were recorded before and after injection (saline or ketamine 20 mg/kg) from male Wistar rats. A separate group of rats was used to study nares blockade. To block the nares, rats were anesthetised and a silicon occluder was inserted into one or both nares. Controls were exposed to initial isoflurane for a comparable amount of time but without blockade. Rats were given recovery and then injected with ketamine. RESULTS: Ketamine immediately increased exploratory fast sniffing (4‑10 Hz), which correlated with increases in locomotor activity and HFO power. Saline injection did not substantially alter these measures. Nasal respiration entrained bursts of ketamine HFO recorded in the OB on a cycle‑by‑cycle basis. Further, ketamine-induced HFO was attenuated unilaterally by naris blockade on the same side. Bilateral naris blockade reduced power and frequency of HFO and also reduced hyperactivity produced by ketamine. CONCLUSIONS: Our results suggest that nasal respiration is a powerful drive of HFO after injection of ketamine in the OB. These findings may explain previous observations that ketamine-HFO couples to slower frequencies. Functional nasal respiration appears to be critical for the emergence of both HFO and hyperactivity produced by ketamine.
INTRODUCTION: Around 50 million people worldwide are affected by epilepsy. Despite efficiency and steady development of pharmacological treatments, every third patient suffers from intractable seizures. A surgical intervention may be the only solution in these cases. To identify the region for resection, neurosurgeons implant intracranial and subdural electrodes which are used to localize the epileptogenic zone from the measured potentials. AIM(S): Providing better tools for reliable reconstruction of sources of brain activity may lead to more precise localization of the seizure’s origin and better surgical outcomes. To reconstruct sources of brain activity, we use kernel approximation methods for the inverse problem (the reconstruction itself). We model the electric field generated by the neural activity (the forward problem) with finite element method (FEM). We use FEM as it enables the inclusion of realistic head anatomy and tissue properties in the model. METHOD(S): Here we present a method – kernel Electrical Source Imaging (kESI) – of reconstruction of the activity underlying the measured potentials. kESI allows us to use information from arbitrarily placed electrodes and may integrate patient-specific anatomical information which increases precision of localization of epileptogenic zone for a specific patient. RESULTS: The preliminary results are promising. The major advantage of kESI over previous work is that it accounts for spatial variations of brain conductivity and can take into account patient-specific brain and skull anatomy. CONCLUSIONS: Nevertheless, further work is necessary to bring this method to the level of clinical application. FINANCIAL SUPPORT: Project funded from the Polish National Science Centre’s OPUS grant (2015/17/B/ ST7/04123).
BACKGROUND AND AIMS: A common paradigm in electrophysiology is a study of responses of neural tissue to voltage or current stimulation. Even a short stimulation can elicit artifacts lasting for tens of milliseconds after stimulation, of amplitude comparable to the responses to be measured. The ability to automatically detect and remove stimulation artifacts from physiological recordings would improve the reliability of biological conclusions obtained in the experiments. In this work we show how to assess and subtract such artifacts from multi-electrode array (MEA) recordings. METHODS: In acute brain slice preparations of the rat somatosensory cortex we investigated in-vitro evoked extracellular responses using 60-channel MEAs (Multichannel Systems). We applied voltage stimulations at different locations under artificial cerebro spinal fluid (ACSF) (a) without tissue, (b) with tissue and (c) with tissue after application of sodium channel blocker (TTX).   RESULTS: We have considered several models of artifact dependence on the distance from the stimulating electrode and on time from the onset of stimulation. We found that the best model for prediction of the artifact on every electrode for physiological recordings is its value recorded on slices after TTX application. The slice need not be the same. A proxy from recordings with just the ACSF can be used to construct a still acceptable model. Using Independent Component Analysis and Current Source Density reconstruction we investigate the structure of the artifact and example physiological responses. CONCLUSION: With the help of extracellular recordings of slices after application of TTX it is possible to reliably estimate stimulation artifacts interfering with physiological responses and thus improving the quality and precision of data obtained in such experiments.
INTRODUCTION: Long-term synaptic plasticity (LTSP) is a complex phenomenon. Experiments utilizing different LTSP-inducing paradigms have demonstrated activation of multiple signaling pathways and uncovered differences in neuromodulatory dependence. For example, dopaminergic (D1R) activation can retroactively convert spike-timing dependent depression to potentiation. On the other hand, inhibition of beta‑adrenergic (βAR) and not D1R activation can block induction of late, protein-synthesis dependent phase of LTSP (L‑LTSP) evoked by rate‑dependent paradigms (RTP). This is confusing because activation of both D1R and βAR increase cAMP activity and activate its targets. AIM(S): Understand the impact of differences in temporal patterns of synaptic and neuronal activity on activation of signaling pathways and signal transduction. METHOD(S): We used two detailed, multi-compartmental, morphologically realistic models of the CA1 neuron: 1) a conductance‑based neuron model, and 2) a stochastic reaction‑diffusion model of calcium‑, βAR‑, and D1R‑activated signaling pathways underlying LTSP. The latter model allows for simulating, monitoring, and controlling molecular concentrations in a dendritic spine and a dendritic segment. RESULTS: Modulation of dendritic potassium ion channels (e.g., SK, Kv1.1) by protein kinase A (PKA) may explain the observed differences in neuromodulatory requirements of STDP and RTP. To predict whether paradigms eliciting spike-timing dependent plasticity will induce L-LTSP, we studied the activity of key molecules implicated in plasticity, such as calcium calmodulin-dependent protein kinase II (CaMKII) and PKA. In the spine, we studied molecular species that are involved in actin cytoskeleton remodelling, and in the dendrite – particularly those that play a role in protein synthesis. CONCLUSIONS: These preliminary results suggest that molecular activity micro-spatial scales can predict the induction of L‑LTSP.
INTRODUCTION: Current Source Density (CSD) is spatially smoothed transmembrane activity of the neurons. Local Field Potential (LFP) is the electric potential generated by ionic currents in the neural tissue and it is directly related to the CSD. LFP is relatively easily accessible experimentally but due to the long range of electric field, it is difficult to interpret. CSD needs to be calculated but it reflects the local neural activity directly. Since the currents directly reflect neuronal computations, using electric potentials (LFP’s) to infer performed computation may lead to misinterpretations. AIM(S): 1) Discuss challenges arising in multielectrode LFP and CSD analysis, in particular case where direct analysis of LFPs can lead to misinterpretation. 2) Show that the kernel Current Source Density reconstruction method (kCSD) gives a better insight into the underlying phenomena than the observed potentials, and to show the limits and uncertainties yielded by the method. 3) Present the kCSD-python toolbox for CSD analysis. METHOD(S): All of the modeling and computations was done in Python and tested on model data. Potentials were calculated using assumed physical models of tissue. The kCSD library in Python is available at: https://github.com/ Neuroinflab/kCSD‑python. RESULTS: We show examples where the LFP’s can ‘hide’ more complex underlying CSD patterns and how the kCSD can reconstruct those sources, depending on the number and configuration of recording electrodes. CONCLUSIONS: Complex CSD patterns studied at the resolution of few electrodes can be obscured if only direct LFP analysis is used. The kCSD method can help to recover them. The main limiting factors are the number of recording electrodes and their configuration. FINANCIAL SUPPORT: This work was supported by EC-FP7-PEOPLE sponsored NAMASEN Marie-Curie ITN grant 264872, Polish Ministry for Science and Higher Education grant 2948/7.PR/2013/2, Narodowe Centrum Nauki grants 2013/08/W/NZ4/00691 and 2015/17/B/ ST7/04123.
Passive propagation of electric fields can induce ap‑ parent coherence in local field potentials (LFP) record‑ ed over distances of several millimetres hindering their analysis. This issue can be overcome with current source density analysis (CSD). Mathematically, CSD reconstruc‑ tion is an ill‑posed problem which means that many dif‑ ferent possible current source distributions fit the mea‑ sured LFP and the challenge is to find the most probable one. Furthermore, LFP recordings are always noisy, par‑ ticularly in data obtained from freely moving animals, which may affect CSD estimation. Previously, we pro‑ posed the kernel CSD (kCSD) method for reconstruction of the spatial distribution of sources and sinks in biologi‑ cal tissue from noisy data. Here we show how the method parameters can be estimated quickly and reliably using an L‑curve approach. We demonstrated the feasibility of this approach on model data and illustrated its power in the analysis of LFP recordings from linear probes im‑ planted in the olfactory bulb (OB) of freely moving rats. We focused on ketamine‑induced high frequency oscilla‑ tions (HFO, 120‑200 Hz) since, to date, the locus of gen‑ eration of HFO remains unclear. kCSD is a model‑based CSD estimation method which assumes a flexible model of CSD and estimates its parameters from data. L‑curve is a technique for finding the optimal way of weighting the complexity of the model against the difference between model predictions and the actual set of measurements. The LFPs we analysed were recorded from freely moving rats implanted with a 32‑channel linear probe targeted to the OB. Recordings were made at baseline and post in‑ jection of 25 mg/kg ketamine (i.p.). To examine the faith‑ fulness of kCSD reconstruction we tested this method on model LFPs from ground truth data. We showed that the L‑curve provides reliable and practical estimation of regularization parameters for robust kCSD estimation of sources from noisy LFPs. After validating this method, we estimated the current sources from recordings in the rat OB. We found HFO dipoles close to the mitral layer, whereas above it there was little evidence of any phase reversal. kCSD with L‑curve is a robust method for esti‑ mation of current sources from noisy data. It facilitates localization of the sources of abnormal HFO activity to a specific layer within olfactory bulb which is consistent with histology.
INTRODUCTION: The low-frequency part of extracellular potential, called the Local Field Potential (LFP), is a useful measure of neural systems activity. However, a direct interpretation of LFP is problematic as it is not a local measure – each electrode may record activity observed millimeters away from source. Estimation of current source density (CSD), the volume density of net transmembrane currents, has become a convenient way to deal with this problem. AIM(S): The aim of the study is to investigate the properties of kCSD method to develop a procedure which will facilitate optimal usage of the presented method in complicated experimental scenarios, for complex measurement setups etc. METHOD(S): In the study we use kCSD method which estimates the sources in a family of allowed CSD distributions of dimensionality larger than the number of measurements. To identify the parameters of the method leading to optimal source estimation, a statistical technique of cross-validation is used. We perform this study using Python programming language with several types of known (model) reference data and different electrodes setups. We employ singular value decomposition (SVD) method to study the internal properties of kCSD reconstruction. RESULTS: To examine the influence of the measurement setup on the reconstruction capability of the kCSD method we performed simulated study. We present error maps of CSD estimation which give us valuable insight into kCSD reconstruction quality. CONCLUSIONS: The quality of CSD estimation significantly depends on the measurement setup. This study enables the researchers to check how much they can trust the obtained kCSD reconstruction for a given setup and specific collection of recordings. FINANCIAL SUPPORT: This work was supported by EC-FP7-PEOPLE sponsored NAMASEN Marie-Curie ITN grant 264872, Polish Ministry for Science and Higher Education grant 2948/7.PR/2013/2, Narodowe Centrum Nauki grants 2013/08/W/NZ4/00691 and 2015/17/B/ST7/04123.
Local field potentials (LFP), the low-frequency part of extracellular electric potential, reflect dendritic processing of synaptic inputs to neuronal populations. Today one can easily record simultaneous potentials from multiple contacts. Due to the nature of electric field each electrode may record activity of sources millimeters away which leads to significant correlations between signals and complicates their analysis. Whenever possible it is convenient to estimate the current source density (CSD), the volume density of net transmembrane currents, which generate the LFP. CSD directly reflects the local neural activity and CSD analysis is often used to analyze LFP. We present here a general, nonparametric method for CSD estimation based on kernel techniques, which can take into account known anatomy or physiology of the studied structure. Using data from a simulated large scale model of thalamo-cortical column we also show how CSD analysis combined with independent component analysis (ICA) can reveal information on activity of individual cell populations. Research supported by grants 5428/B/P01/2010/39, POIG.02.03.00- 00-003/09, POIG.02.03.00-00-018/08.
INTRODUCTION: Eco-HAB is an open source system for automated measurements and analysis of social preferences and in-cohort sociability in mice. It requires no contact between a human experimenter and tested animals. In Eco-HAB, group-housed mice live in a spacious, four-compartment, resembling natural burrows. It allows an assessment of the tendency of mice to voluntarily spend time together in ethologically relevant mouse group sizes. Results are obtained faster, with less manpower needed and without confounding factors. AIM(S): The aim of the of this study is to develop measures for the EcoHAB system, which could well describe social relations in a group of mice. We test the proposed measures in experiments with four FX WT and three FX KO groups. We expected that FX KO mice would have disturbed social skills comparing to FX WT. METHOD(S): We developed a dedicated workflow for analysis of social interactions based on analysis of the decision patterns. For each pair of mice, one mouse is a leader, the other is a follower. After the leader changes the room, the follower’s reaction in a 3-second window is analysed. If the follower acts on the leader’s movement and follows it, the pattern is classified as “following”; otherwise it is “evasion”. Lack of follower’s reaction is ignored. The numbers of interactions for each pair and distribution of the patterns were obtained. To characterize the relations between the mice in selected time windows we used binomial model. We also studied changes of these relation in time and their distribution in mice groups. RESULTS: Our study proved that FX KO mice have significantly less interactions within a pair than FX WT. What’s more, FX WT are following each other more often and the character of interaction is more stable. CONCLUSIONS: EcoHAB is a good environment for conducting advanced analysis of mice social interactions. Proposed measures show significant difference between WT and KO group and are a promising tool to study social interactions.
INTRODUCTION: Over the past decade, we and other groups have shown that ketamine and other NMDA receptor antagonists evoke high‑frequency oscillations (HFO; 130‑180 Hz) in a variety of rodent cortical and subcortical regions. AIM(S): Our recent studies show that the olfactory bulb (OB) appears to be particularly important for the generation of this activity. To date, this activity has mainly been recorded in awake rats; however, there is some evidence that fast oscillation can be recorded in the OB of rodents under ketamine xylazine anesthesia. METHOD(S): LFPs in the OB were recorded using twisted stainless-steel electrodes in rats under ketamine 100 mg/kg + xylazine 10 mg/kg anesthesia (KX) or a subanesthetic dose of ketamine 20 mg/kg. In a second study, rats were implanted with thermocouples for simultaneous recording of nasal respiration and LFPs in the OB. In a third study, 32 channel silicon probes were used to record LFPs under KX. KX was associated with the emergence of a fast oscillations, around 120 Hz (which we termed KX-HFO) that occurred in bursts nested on slower oscillations. This is similar to HFO that occurs in awake rats following subanesthetic doses of ketamine. KX‑HFO were attenuated by unilateral naris blockade and reversed phase close to the mitral layer – also similar to the awake state. RESULTS: Simultaneous recordings from the nasal cavity (with thermocouples) and LFPs showed that KX-HFO was tightly coupled to nasal respiration, around 2 Hz. Spatial profile of LFPs recorded across the OB revealed strong HFO current sources close to the mitral layer that was preceded by a large current sink (around 2 Hz) more ventrally (in the extraplexiform/glomerular layers). CONCLUSIONS: Nasal respiration drives afferent input to the OB that produces corresponding large current sinks (local depolarization) in the OB which under KX anesthesia (and more generally NMDAR blockade) leads to the emergence of HFO by stimulating mitral/ tufted neurons at their apical dendrites.
INTRODUCTION: Optogenetics allows to stimulate selected neuronal populations with high temporal resolution but the spatio‑temporal extent of resulting effects is not well characterized. AIM(S): Experiment were aimed to evaluate spatial distribution of the potentials and currents evoked by light impulses in the channelrhodopsin-transfected rat cortex. METHOD(S): Rats were injected with viral vector introducing ChR2 into large portion of somatosensory cortex. 2–3 weeks later we performed acute in vivo experiments recording multichannel local field potentials evoked (EP) by a blue light delivered either to the cortical surface (surf-stim) or into the cortex (deep-stim). We analyzed spatio-temporal patterns of EPs and their 2-D current source density (CSD) profiles (kernel CSD method, https://github. com/Neuroinflab/kCSD‑python). RESULTS: Our preliminary results indicated that light evoked potentials consisted of early waves, resulting from opening ChR2 channels, overlapping with later components related to the synaptic spread of activity within cortical network. As expected, largest EPs were recorded close to the fiber tip, in layer 2–3 with surf‑stim and layer 5 with deep-stim. Longer impulses (10 ver 1 ms) evoked around 20% stronger responses. Up to 600–800 µm from a light source EPs sustained ~50% of max amplitude. However, CSD analysis indicated that after surf-stim the early current sink (1–2 ms) was restricted to ~400 µm in layer 2–3. Later, postsynaptic sink developed at 5–8 ms in layer 5. Later components had wider lateral spread across few columns with clear reflection of cortical layering. After intra-cortical light delivery activity seemed to spread within, not across the cortical columns. CONCLUSIONS: For well controlled use of optogenetics it is not enough to ensure light beam of sufficient strength. The localization of the fiber tip can have specific impact on the activity developing within local neuronal network. FINANCIAL SUPPORT: Supported by Polish National Science Centre grant 2013/08/W/NZ4/00691.
Most of recent studies of the role of cortical feedback in thalamocortical loop focused on its effect on thalamo-cortical relay (TCR) cells of the dorsal lateral geniculate nucleus (LGN). In a previous, physiological study we showed in cat visual system that cessation of cortical input decreased spontaneous activity of TCR cells and increased spontaneous firing of recurrent inhibitory interneurons located in the perigeniculate neucleus (PGN). To identify underlying mechanisms we studied several networks of point neurons with varied membrane properties, synaptic weights and axonal delays in NEURON simulator. We considered six network topologies. All models were robust against changes of axonal delays except for the delay between LGN feed-forward (f-f) interneuron and TCR cell. The best representation of physiological results gave models including reciprocally connected PGN cells driven by the cortex assuming slow decay of intracellular calcium. This indicates that thalamic reticular nucleus plays an essential role in the cortical influence over thalamo-cortical relay cells while the thalamic f-f interneurons are not essential in this process. The models revealed also that dependence of the PGN activity on the rate of calcium removal can be one of the key factors determining TCR response to diminished cortical input.
INTRODUCTION: Extracellular potentials, such as the Local Field Potentials (LFPs), are routinely measured in numerous electrophysiological experiments. LFP can carry valuable information about the electric properties of the tissue, however analysis of the recorded signal is usually a complex task. Apart from basic preparation, such as bandpass filtering and artifact removal, many other analytic methods have been proposed for the LFP study. Here we discuss methods for estimation of electric sources and sinks in brain tissue (Current Source Density, CSD) and methods to estimate connectivity in small networks, and their utility in analysis of cortical recordings in rats. AIM(S): Comparison of the effective connectivity and the structure of sinks and sources in cortical columns during whisker stimulations. METHOD(S): Analytic methods: kernel Current Source Density and Modular Connectivity Factorization (MCF) applied to LFP recordings and simulated data from cortical column. Experimental methods: Simultaneous multielectrode in vivo recordings from both hemispheres of the rats brain. RESULTS: Preliminary studies show different distribution of the current sources in contralateral to ipsilateral hemisphere during whisker stimulation in rats. Comparison of the hemispheres from deprived rats shows an extension of the whisker representation in the barrel cortex receptive field. CONCLUSIONS: KCSD method showssignificant differences in current sources localization in contralateral to ipsilateral hemisphere. Modular Connectivity Factorization method applied to LFP recordings from simulated data separates cortical column layers into interpretable modules. Physiological interpretation of the results needs further validation on the cortical column model. FINANCIAL SUPPORT: Instytut Biologii Doświadczalnej im. Marcelego Nenckiego Polska Akademia Nauk, Warsaw, Poland, Uniwersytet Warszawski, Warsaw, Poland
To test methods of local field potential (LFP) analysis we need realistic ground truth data which demands plausible models of neural activity and of physical properties of the setup, tissue, and the electrodes. To interpret the recordings we often reconstruct the Current Source Density (CSD) from the LFP. In this work we study the effect of realistic conductivity profiles and the slice geometry on (1) computation of LFP generated by cell populations embedded in slice, as would be measured on multi-electrode array (MEA), and (2) current source density (CSD) reconstruction in the slice from such potentials. We show that the method of images approximates solution through finite elements well while being much more efficient computationally. Inclusion of slice properties with homogeneous and uniform conductivity in the slice noticeably modifies the observed activity (LFP) but inhomogeneity and anisotropy do not further change the profile and amplitude of the LFP. Supported with grants: IP2011 030971, N N303 542839, FP7-PEOPLE-2010-ITN 264872, POIG.02.03.00-00-018/08, POIG.02.03.00-00-003/09.
Over the past decade, high frequency oscillations (HFO, 130‑180 Hz) recorded in field potentials have been shown to be robustly potentiated by ketamine adminis‑ tration. This rhythm has been recorded in functionally and neuroanatomically diverse cortical and subcortical regions, most notably in the ventral striatum. Howev‑ er, the precise locus of generation remains largely un‑ known. There is compelling evidence that olfactory regions can drive oscillations in distant areas. Here, we tested the hypothesis that the olfactory bulb (OB) exerts a top‑down role in the generation of ketamine‑HFO. We examined the effect of ketamine on electrophysiologi‑ cal activity of the OB and ventral striatum in vivo. Field potential recordings, local inhibition, naris blockade, current source density and unit recordings were used. Ketamine‑HFO in the OB was larger and preceded HFO recorded in the ventral striatum. Granger causality anal‑ ysis was consistent with directional flow from the OB. Unilateral local inhibition of the OB, and naris blockade, attenuated HFO recorded locally and in the ventral stri‑ atum. Within the OB, current source density analysis revealed HFO current dipoles close to the mitral layer and unit firing of mitral/tufted cells was phase locked to HFO. Our results demonstrate a hierarchical top‑down relationship between ketamine‑HFO in the OB and the ventral striatum. The OB plays a primary role in the gen‑ eration of ketamine‑HFO and orchestrates this activity in a distant region. These findings provide a new con‑ ceptual understanding on how ketamine influences fun‑ damental brain activity which may have implications for schizophrenia.
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