Local contribution to the somatosensory evoked potentials in rat's thalamus.

Local Field Potential (LFP), despite its name, often reflects remote activity. Depending on the orientation and synchrony of their sources, both oscillations and more complex waves may passively spread in brain tissue over long distances and be falsely interpreted as local activity at such distant recording sites. Here we show that the whisker-evoked potentials in the thalamic nuclei are of local origin up to around 6 ms post stimulus, but the later (7-15 ms) wave is overshadowed by a negative component reaching from cortex. This component can be analytically removed and local thalamic LFP can be recovered reliably using Current Source Density analysis. We used model-based kernel CSD (kCSD) method which allowed us to study the contribution of local and distant currents to LFP from rat thalamic nuclei and barrel cortex recorded with multiple, non-linear and non-regular multichannel probes. Importantly, we verified that concurrent recordings from the cortex are not essential for reliable thalamic CSD estimation. The proposed framework can be used to analyze LFP from other brain areas and has consequences for general LFP interpretation and analysis.

kCSD-python, reliable current source density estimation with quality control.

Interpretation of extracellular recordings can be challenging due to the long range of electric field. This challenge can be mitigated by estimating the current source density (CSD). Here we introduce kCSD-python, an open Python package implementing Kernel Current Source Density (kCSD) method and related tools to facilitate CSD analysis of experimental data and the interpretation of results. We show how to counter the limitations imposed by noise and assumptions in the method itself. kCSD-python allows CSD estimation for an arbitrary distribution of electrodes in 1D, 2D, and 3D, assuming distributions of sources in tissue, a slice, or in a single cell, and includes a range of diagnostic aids. We demonstrate its features in a Jupyter Notebook tutorial which illustrates a typical analytical workflow and main functionalities useful in validating analysis results.

Pylabianca: comprehensive and user­friendly Python package for single­neuron data analysis.

In the area of electrophysiology, the availability of comprehensive and user­friendly tools for single-neuron data processing, statistical analysis, and fast, intuitive data visualization is limited. To address this gap, we introduce pylabianca, a Python library tailored for robust single and multi­unit data processing. Pylabianca leverages the power of standard Python packages and adopts the application programming interface of MNE­Python, one of the most widely used electrophysiology packages. One of pylabianca's primary objectives is to provide a low entry threshold for scientists, requiring only basic Python programming skills. Pylabianca was designed to streamline most common analyses of single neuron data, and provide convenient data structures to serve as a foundation for building custom analysis pipelines. We believe that pylabianca will contribute to enhancing researchers' capabilities and efficiency in the field of single-neuron electrophysiology.

The Role of Interhemispheric Interactions in Cortical Plasticity.

Despite the fact that there is a growing awareness to the callosal connections between hemispheres the two hemispheres of the brain are commonly treated as independent structures when peripheral or cortical manipulations are applied to one of them. The contralateral hemisphere is often used as a within-animal control of plastic changes induced onto the other side of the brain. This ensures uniform conditions for producing experimental and control data, but it may overlook possible interhemispheric interactions. In this paper we provide, for the first time, direct proof that cortical, experience-dependent plasticity is not a unilateral, independent process. We mapped metabolic brain activity in rats with 2-[14C] deoxyglucose (2DG) following experience-dependent plasticity induction after a month of unilateral (left), partial whiskers deprivation (only row B was left). This resulted in ∼45% widening of the cortical sensory representation of the spared whiskers in the right, contralateral barrel field (BF). We show that the width of 2DG visualized representation is less than 20% when only contralateral stimulation of the spared row of whiskers is applied in immobilized animals. This means that cortical map remodeling, which is induced by experience-dependent plasticity mechanisms, depends partially on the contralateral hemisphere. The response, which is observed by 2DG brain mapping in the partially deprived BF after standard synchronous bilateral whiskers stimulation, is therefore the outcome of at least two separately activated plasticity mechanisms. A focus on the integrated nature of cortical plasticity, which is the outcome of the emergent interactions between deprived and non-deprived areas in both hemispheres may have important implications for learning and rehabilitation. There is also a clear implication that there is nothing like "control hemisphere" since any plastic changes in one hemisphere have to have influence on functioning of the opposite one.

What we can and what we cannot see with extracellular multielectrodes.

Extracellular recording is an accessible technique used in animals and humans to study the brain physiology and pathology. As the number of recording channels and their density grows it is natural to ask how much improvement the additional channels bring in and how we can optimally use the new capabilities for monitoring the brain. Here we show that for any given distribution of electrodes we can establish exactly what information about current sources in the brain can be recovered and what information is strictly unobservable. We demonstrate this in the general setting of previously proposed kernel Current Source Density method and illustrate it with simplified examples as well as using evoked potentials from the barrel cortex obtained with a Neuropixels probe and with compatible model data. We show that with conceptual separation of the estimation space from experimental setup one can recover sources not accessible to standard methods.

Network and synaptic mechanisms underlying high frequency oscillations in the rat and cat olfactory bulb under ketamine-xylazine anesthesia.

Wake-related ketamine-dependent high frequency oscillations (HFO) can be recorded in local field potentials (LFP) from cortical and subcortical regions in rodents. The mechanisms underlying their generation and occurrence in higher mammals are unclear. Unfortunately, anesthetic doses of pure ketamine attenuate HFO, which has precluded their investigation under anesthesia. Here, we show ketamine-xylazine (KX) anesthesia is associated with a prominent 80-130 Hz rhythm in the olfactory bulb (OB) of rats, whereas 30-65 Hz gamma power is diminished. Simultaneous LFP and thermocouple recordings revealed the 80-130 Hz rhythm was dependent on nasal respiration. This rhythm persisted despite surgical excision of the piriform cortex. Silicon probes spanning the dorsoventral aspect of the OB revealed this rhythm was strongest in ventral areas and associated with microcurrent sources about the mitral layer. Pharmacological microinfusion studies revealed dependency on excitatory-inhibitory synaptic activity, but not gap junctions. Finally, a similar rhythm occurred in the OB of KX-anesthetized cats, which shared key features with our rodent studies. We conclude that the activity we report here is driven by nasal airflow, local excitatory-inhibitory interactions, and conserved in higher mammals. Additionally, KX anesthesia is a convenient model to investigate further the mechanisms underlying wake-related ketamine-dependent HFO.

Spreading Depressions and Periinfarct Spreading Depolarizations in the Context of Cortical Plasticity.

Studies of cortical function-recovery require a comparison between normal and post-stroke conditions that lead to changes in cortical metaplasticity. Focal cortical stroke impairs experience-dependent plasticity in the neighboring somatosensory cortex and usually evokes periinfarct depolarizations (PiDs) - spreading depression-like waves. Experimentally induced spreading depressions (SDs) affect gene expression and some of these changes persist for at least 30 days. In this study we compare the effects of non-stroke depolarizations that impair cortical experience-dependent plasticity to the effects of stroke, by inducing experience-dependent plasticity in rats with SDs or PiDs by a month of contralateral partial whiskers deprivation. We found that whiskers' deprivation after SDs resulted in normal cortical representation enlargement suggesting that SDs and PiDs depolarization have no influence on experience-dependent plasticity cortical map reorganization. PiDs and the MMP-9, -3, -2 or COX-2 proteins, which are assumed to influence metaplasticity in rats after stroke were compared between SDs induced by high osmolarity KCl solution and the PiDs that followed cortical photothrombotic stroke (PtS). We found that none of these factors directly caused cortical post-stroke metaplasticity changes. The only significant difference between stoke and induced SD was a greater imbalance in interhemispheric activity equilibrium after stroke. The interhemispheric interactions that were modified by stroke may therefore be promising targets for future studies of post-stroke experience-dependent plasticity and of recuperation studies.

Nasal respiration is necessary for ketamine-dependent high frequency network oscillations and behavioral hyperactivity in rats.

Changes in oscillatory activity are widely reported after subanesthetic ketamine, however their mechanisms of generation are unclear. Here, we tested the hypothesis that nasal respiration underlies the emergence of high-frequency oscillations (130-180 Hz, HFO) and behavioral activation after ketamine in freely moving rats. We found ketamine 20 mg/kg provoked "fast" theta sniffing in rodents which correlated with increased locomotor activity and HFO power in the OB. Bursts of ketamine-dependent HFO were coupled to "fast" theta frequency sniffing. Theta coupling of HFO bursts were also found in the prefrontal cortex and ventral striatum which, although of smaller amplitude, were coherent with OB activity. Haloperidol 1 mg/kg pretreatment prevented ketamine-dependent increases in fast sniffing and instead HFO coupling to slower basal respiration. Consistent with ketamine-dependent HFO being driven by nasal respiration, unilateral naris blockade led to an ipsilateral reduction in ketamine-dependent HFO power compared to the control side. Bilateral nares blockade reduced ketamine-induced hyperactivity and HFO power and frequency. These findings suggest that nasal airflow entrains ketamine-dependent HFO in diverse brain regions, and that the OB plays an important role in the broadcast of this rhythm.

The olfactory bulb is a source of high-frequency oscillations (130-180 Hz) associated with a subanesthetic dose of ketamine in rodents.

High-frequency neuronal population oscillations (HFO, 130-180 Hz) are robustly potentiated by subanesthetic doses of ketamine. This frequency band has been recorded in functionally and neuroanatomically diverse cortical and subcortical regions, notably ventral striatal areas. However, the locus of generation remains largely unknown. There is compelling evidence that olfactory regions can drive oscillations in distant areas. Here we tested the hypothesis that the olfactory bulb (OB) is a locus for the generation of HFO following a subanesthetic dose of ketamine. The effect of ketamine on the electrophysiological activity of the OB and ventral striatum of male Wistar rats was examined using field potential and unit recordings, local inhibition, naris blockade, current source density and causality estimates. Ketamine-HFO was of larger magnitude and was phase-advanced in the OB relative to ventral striatum. Granger causality analysis was consistent with the OB as the source of HFO. Unilateral local inhibition of the OB and naris blockade both attenuated HFO recorded locally and in the ventral striatum. 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 reveal the OB as a source of ketamine-HFO which can contribute to HFO in the ventral striatum, known to project diffusely to many other brain regions. These findings provide a new conceptual understanding on how changes in olfactory system function may have implications for neurological disorders involving NMDA receptor dysfunction such as schizophrenia and depression.

Dynamic JUNQ inclusion bodies are asymmetrically inherited in mammalian cell lines through the asymmetric partitioning of vimentin.

Aging is associated with the accumulation of several types of damage: in particular, damage to the proteome. Recent work points to a conserved replicative rejuvenation mechanism that works by preventing the inheritance of damaged and misfolded proteins by specific cells during division. Asymmetric inheritance of misfolded and aggregated proteins has been shown in bacteria and yeast, but relatively little evidence exists for a similar mechanism in mammalian cells. Here, we demonstrate, using long-term 4D imaging, that the vimentin intermediate filament establishes mitotic polarity in mammalian cell lines and mediates the asymmetric partitioning of damaged proteins. We show that mammalian JUNQ inclusion bodies containing soluble misfolded proteins are inherited asymmetrically, similarly to JUNQ quality-control inclusions observed in yeast. Mammalian IPOD-like inclusion bodies, meanwhile, are not always inherited by the same cell as the JUNQ. Our study suggests that the mammalian cytoskeleton and intermediate filaments provide the physical scaffold for asymmetric inheritance of dynamic quality-control JUNQ inclusions. Mammalian IPOD inclusions containing amyloidogenic proteins are not partitioned as effectively during mitosis as their counterparts in yeast. These findings provide a valuable mechanistic basis for studying the process of asymmetric inheritance in mammalian cells, including cells potentially undergoing polar divisions, such as differentiating stem cells and cancer cells.