Ribosome-Associated Vesicles promote activity-dependent local translation.

Local protein synthesis in axons and dendrites underpins synaptic plasticity. However, the composition of the protein synthesis machinery in distal neuronal processes and the mechanisms for its activity-driven deployment to local translation sites remain unclear. Here, we employed cryo-electron tomography, volume electron microscopy, and live-cell imaging to identify Ribosome-Associated Vesicles (RAVs) as a dynamic platform for moving ribosomes to distal processes.

Believing is seeing - the deceptive influence of bias in quantitative microscopy.

The visual allure of microscopy makes it an intuitively powerful research tool. Intuition, however, can easily obscure or distort the reality of the information contained in an image. Common cognitive biases, combined with institutional pressures that reward positive research results, can quickly skew a microscopy project towards upholding, rather than rigorously challenging, a hypothesis.

A Kalirin missense mutation enhances dendritic RhoA signaling and leads to regression of cortical dendritic arbors across development.

Normally, dendritic size is established prior to adolescence and then remains relatively constant into adulthood due to a homeostatic balance between growth and retraction pathways. However, schizophrenia is characterized by accelerated reductions of cerebral cortex gray matter volume and onset of clinical symptoms during adolescence, with reductions in layer 3 pyramidal neuron dendritic length, complexity, and spine density identified in multiple cortical regions postmortem. Nogo receptor 1 (NGR1) activation of the GTPase RhoA is a major pathway restricting dendritic growth in the cerebral cortex.

The Role of SPECT and PET in Epilepsy.

The purpose of this article is to summarize the role of molecular imaging of the brain by use of SPECT, FDG PET, and non-FDG PET radiotracers in epilepsy. Quantitative image analysis with PET and SPECT has increased the diagnostic utility of these modalities in localizing epileptogenic onset zones. A multi-modal platform approach integrating the functional imaging of PET and SPECT with the morphologic information from MRI in presurgical evaluation of epilepsy can greatly improve outcomes.

Voltage-based automated detection of postictal generalized electroencephalographic suppression: Algorithm development and validation.

Objective: Postictal generalized electroencephalographic suppression (PGES) is a pattern of low-voltage scalp electroencephalographic (EEG) activity following termination of generalized seizures. PGES has been associated with both sudden unexplained death in patients with epilepsy and therapeutic efficacy of electroconvulsive therapy (ECT). Automated detection of PGES epochs may aid in reliable quantification of this phenomenon.

A Comprehensive Integrated Anatomical and Molecular Atlas of Rat Intrinsic Cardiac Nervous System.

We have developed and integrated several technologies including whole-organ imaging and software development to support an initial precise 3D neuroanatomical mapping and molecular phenotyping of the intracardiac nervous system (ICN). While qualitative and gross anatomical descriptions of the anatomy of the ICN have each been pursued, we here bring forth a comprehensive atlas of the entire rat ICN at single-cell resolution. Our work precisely integrates anatomical and molecular data in the 3D digitally reconstructed whole heart with resolution at the micron scale.

Ribosome-associated vesicles: A dynamic subcompartment of the endoplasmic reticulum in secretory cells.

The endoplasmic reticulum (ER) is a highly dynamic network of membranes. Here, we combine live-cell microscopy with in situ cryo-electron tomography to directly visualize ER dynamics in several secretory cell types including pancreatic β-cells and neurons under near-native conditions. Using these imaging approaches, we identify a novel, mobile form of ER, ribosome-associated vesicles (RAVs), found primarily in the cell periphery, which is conserved across different cell types and species.

Intrinsic network reactivity differentiates levels of consciousness in comatose patients.

Objective: We devise a data-driven framework to assess the level of consciousness in etiologically heterogeneous comatose patients using intrinsic dynamical changes of resting-state Electroencephalogram (EEG) signals.

Methods: EEG signals were collected from 54 comatose patients (GCS ⩽ 8) and 20 control patients (GCS > 8). We analyzed the EEG signals using a new technique, termed Intrinsic Network Reactivity Index (INRI), that aims to assess the overall lability of brain dynamics without the use of extrinsic stimulation.

EEG dynamical correlates of focal and diffuse causes of coma.

Background: Rapidly determining the causes of a depressed level of consciousness (DLOC) including coma is a common clinical challenge. Quantitative analysis of the electroencephalogram (EEG) has the potential to improve DLOC assessment by providing readily deployable, temporally detailed characterization of brain activity in such patients. While used commonly for seizure detection, EEG-based assessment of DLOC etiology is less well-established.

Postoperative seizure freedom does not normalize altered connectivity in temporal lobe epilepsy.

Objectives: Specific changes in the functional connectivity of brain networks occur in patients with epilepsy. Yet whether such changes reflect a stable disease effect or one that is a function of active seizure burden remains unclear. Here, we longitudinally assessed the connectivity of canonical cognitive functional networks in patients with intractable temporal lobe epilepsy (TLE), both before and after patients underwent epilepsy surgery and achieved seizure freedom.

Contributions of space-clamp errors to apparent time-dependent loss of Mg block induced by NMDA.

-methyl-d-aspartate receptors (NMDARs) govern synaptic plasticity, development, and neuronal response to insult. Prolonged activation of NMDARs such as during an insult may activate secondary currents or modulate Mg sensitivity, but the conditions under which these occur are not fully defined. We reexamined the effect of prolonged NMDAR activation in juvenile mouse hippocampal slices.

A case study of voltage-gated potassium channel antibody-related limbic encephalitis with PET/MRI findings.

Preclinical and clinical studies have demonstrated the significance of inflammation and autoantibodies in epilepsy, and the use of immunotherapies in certain situations has become an established practice. Temporal lobe epilepsy can follow paraneoplastic or nonparaneoplastic limbic encephalitis associated with antibodies directed against brain antigens. Here, we focus on a patient with worsening confusion and temporal lobe seizures despite treatment with antiepileptic medications.

Quantification of bursting and synchrony in cultured hippocampal neurons.

It is widely appreciated that neuronal networks exhibit patterns of bursting and synchrony that are not captured by simple measures such as average spike rate. These patterns can encode information or represent pathological behavior such as seizures. However, methods for quantifying bursting and synchrony are not agreed upon and can be confounded with spike rate measures.

24(S)-Hydroxycholesterol as a Modulator of Neuronal Signaling and Survival.

The major cholesterol metabolite in brain, 24(S)-hydroxycholesterol (24S-HC), serves as a vehicle for cholesterol removal. Its effects on neuronal function, however, have only recently begun to be investigated. Here, we review that nascent work.

Interaction between positive allosteric modulators and trapping blockers of the NMDA receptor channel.

Background And Purpose: Memantine and ketamine are clinically used, open-channel blockers of NMDA receptors exhibiting remarkable pharmacodynamic similarities despite strikingly different clinical profiles. Although NMDA channel gating constitutes an important difference between memantine and ketamine, it is unclear how positive allosteric modulators (PAMs) might affect the pharmacodynamics of these NMDA blockers.

Experimental Approach: We used two different PAMs: SGE-201, an analogue of an endogenous oxysterol, 24S-hydroxycholesterol, along with pregnenolone sulphate (PS), to test on memantine and ketamine responses in single cells (oocytes and cultured neurons) and networks (hippocampal slices), using standard electrophysiological techniques.

Indistinguishable synaptic pharmacodynamics of the N-methyl-D-aspartate receptor channel blockers memantine and ketamine.

Memantine and ketamine, voltage- and activation-dependent channel blockers of N-methyl-d-aspartate (NMDA) receptors (NMDARs), have enjoyed a recent resurgence in clinical interest. Steady-state pharmacodynamic differences between these blockers have been reported, but it is unclear whether the compounds differentially affect dynamic physiologic signaling. In this study, we explored nonequilibrium conditions relevant to synaptic transmission in hippocampal networks in dissociated culture and hippocampal slices.

Impaired and facilitated functional networks in temporal lobe epilepsy.

How epilepsy affects brain functional networks remains poorly understood. Here we investigated resting state functional connectivity of the temporal region in temporal lobe epilepsy. Thirty-two patients with unilateral temporal lobe epilepsy underwent resting state blood-oxygenation level dependent functional magnetic resonance imaging.

Trans-middle temporal gyrus selective amygdalohippocampectomy for medically intractable mesial temporal lobe epilepsy in adults: seizure response rates, complications, and neuropsychological outcomes.

Objective: Selective amygdalohippocampectomy (AHC) has evolved to encompass a variety of techniques to resect the mesial temporal lobe. To date, there have been few large-scale evaluations of trans-middle temporal gyrus selective AHC. The authors examine a large series of patients who have undergone the trans-middle temporal gyrus AHC and assess its clinical and neuropsychological impact.

Synaptic NMDA receptors mediate hypoxic excitotoxic death.

Excessive NMDA receptor activation and excitotoxicity underlies pathology in many neuropsychiatric and neurological disorders, including hypoxia/ischemia. Thus, the development of effective therapeutics for these disorders demands a complete understanding of NMDA receptor (NMDAR) activation during excitotoxic insults. The extrasynaptic NMDAR hypothesis posits that synaptic NMDARs are neurotrophic/neuroprotective and extrasynaptic NMDARs are neurotoxic.

Mapping sensorimotor cortex with slow cortical potential resting-state networks while awake and under anesthesia.

Background: The emerging insight into resting-state cortical networks has been important in our understanding of the fundamental architecture of brain organization. These networks, which were originally identified with functional magnetic resonance imaging, are also seen in the correlation topography of the infraslow rhythms of local field potentials. Because of the fundamental nature of these networks and their independence from task-related activations, we posit that, in addition to their neuroscientific relevance, these slow cortical potential networks could play an important role in clinical brain mapping.

Magnesium induces neuronal apoptosis by suppressing excitability.

In clinical obstetrics, magnesium sulfate (MgSO(4)) use is widespread, but effects on brain development are unknown. Many agents that depress neuronal excitability increase developmental neuroapoptosis. In this study, we used dissociated cultures of rodent hippocampus to examine the effects of Mg(++) on excitability and survival.

Ethanol and vestibular stimulation reveal simple and complex aspects of cerebellar heterogeneity.

Unlike the cerebral cortex, the cerebellum is characterized by a simple histological organization that is relatively uniform throughout. However, molecular characteristics of its constituent elements create a high degree of heterogeneity and complexity resulting in the delineation of modules defined by both parasagittal and anteroposterior boundaries. Eccles notion of the cerebellum as "designed to process input information in some unique and essential manner" may relate to analysis of temporal elements involved in both motor and cognitive behaviors.

Differential effects of axon initial segment and somatodendritic GABAA receptors on excitability measures in rat dentate granule neurons.

GABA(A) receptors are found on the somatodendritic compartment and on the axon initial segment of many principal neurons. The function of axonal receptors remains obscure, although it is widely assumed that axonal receptors must have a strong effect on excitability. We found that activation of GABA(A) receptors on the dentate granule neuron axon initial segment altered excitability by depolarizing the voltage threshold for action potential initiation under conditions that minimally affected overall cell input resistance.

The sticky issue of neurosteroids and GABA(A) receptors.

Endogenous neurosteroids and their synthetic analogs (neuroactive steroids) are potent modulators of GABA(A) receptors. Thus, they are of physiological and clinical relevance for their ability to modulate inhibitory function in the CNS. Despite their importance, fundamental issues of neurosteroid actions remain unresolved.