Level Of Neuronal Activity Research Articles

Heterogeneities in intrinsic excitability and frequency-dependent response properties of granule cells across the blades of the rat dentate gyrus.

The dentate gyrus (DG), the input gate to the hippocampus proper, is anatomically segregated into three different sectors, namely, the suprapyramidal blade, the crest region, and the infrapyramidal blade. Although there are well-established differences between these sectors in terms of neuronal morphology, connectivity patterns, and activity levels, differences in electrophysiological properties of granule cells within these sectors have remained unexplored. Here, employing somatic whole cell patch-clamp recordings from the rat DG, we demonstrate that granule cells in these sectors manifest considerable heterogeneities in their intrinsic excitability, temporal summation, action potential characteristics, and frequency-dependent response properties. Across sectors, these neurons showed positive temporal summation of their responses to inputs mimicking excitatory postsynaptic currents and showed little to no sag in their voltage responses to pulse currents. Consistently, the impedance amplitude profile manifested low-pass characteristics and the impedance phase profile lacked positive phase values at all measured frequencies and voltages and for all sectors. Granule cells in all sectors exhibited class I excitability, with broadly linear firing rate profiles, and granule cells in the crest region fired significantly fewer action potentials compared with those in the infrapyramidal blade. Finally, we found weak pairwise correlations across the 18 different measurements obtained individually from each of the three sectors, providing evidence that these measurements are indeed reporting distinct aspects of neuronal physiology. Together, our analyses show that granule cells act as integrators of afferent information and emphasize the need to account for the considerable physiological heterogeneities in assessing their roles in information encoding and processing.NEW & NOTEWORTHY We employed whole cell patch-clamp recordings from granule cells in the three subregions of the rat dentate gyrus to demonstrate considerable heterogeneities in their intrinsic excitability, temporal summation, action potential characteristics, and frequency-dependent response properties. Across sectors, granule cells did not express membrane potential resonance, and their impedance profiles lacked inductive phase leads at all measured frequencies. Our analyses also show that granule cells manifest class I excitability characteristics, categorizing them as integrators of afferent information.

A Presynaptic Phosphosignaling Hub for Lasting Homeostatic Plasticity

Stable function of networks in the brain requires that synapses adapt their strength to levels of neuronal activity in a durable manner and failures to do so result in cognitive disorders. How such persistent and homeostatic regulation of synaptic connections may be biologically implemented in mammalian synapses remains poorly understood. Here, we have employed optical recordings of vesicle release from single synapses, super-resolution microscopy, and phosphoproteomics and reveal that the level of homeostatic regulation of transmitter release is stored in the phosphorylation state of a single serine (1045) of the central active zone organizer protein RIM1. While we also discovered other phosphosites in RIM1 with differential effects on neurotransmitter output, we only found S1045 to be necessary and sufficient for expression of silencing-induced HP. Furthermore, we show that S1045 is kept phosphorylated by regulated expression of the serine arginine protein kinase 2 (SRPK2) which binds to RIM1 and effectively targets this (and other) AZ proteins. SRPK2-induced upscaling of synaptic release involved formation of additional RIM1 nanoclusters and docked vesicles at the AZ, was not observed in the absence of RIM1 and occluded by RIMS1045E. Our data suggest that SRPK2 and RIM1 present a presynaptic phosphosignalling hub and that the spatial association of a kinase and AZ protein can achieve the persistent regulation of transmitter release required for the homeostatic balance of synaptic coupling of neuronal networks.

Effect of scattered pressures from oscillating microbubbles on neuronal activity in mouse brain under transcranial focused ultrasound stimulation.

Previous studies have indicated that the presence of microbubbles (MBs) during sonication has an impact on neuronal activity, while the underlying mechanisms remain to be revealed. In this study, a model for the scattered pressures produced by the pulsating lipid-encapsulated MBs in mouse brain was developed to numerically investigate the effect of MBs on neuronal activity during transcranial focused ultrasound stimulation. The additional summed scattered pressure (Psummed_scat) from the oscillating MBs was calculated from the model. The level of neuronal activity was experimentally verified using an immunofluorescence assay with antibodies against c-fos. The pressure difference (ΔP) between acoustic pressures at which the same level of neuronal activity is excited by ultrasound stimulation with and without MBs was obtained from the experiments. The results showed that Psummed_scat accounts for about half of the ΔP when the MBs experience a "compression-only" response. The Psummed_scat suddenly increased at a critical acoustic pressure, around which a rapid enhancement of ΔP obtained from experiment also occurred. This work suggested that the additional scattered pressures from pulsating MBs are probably a mechanism that affects neuronal activity under transcranial focused ultrasound stimulation.

Evaluation of the Cunningham Panel™ in pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS): Changes in antineuronal antibody titers parallel changes in patient symptoms

ObjectiveThis retrospective study examined whether changes in patient pre- and post-treatment symptoms correlated with changes in anti-neuronal autoantibody titers and the neuronal cell stimulation assay in the Cunningham Panel in patients with Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection (PANDAS), and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). MethodsIn an analysis of all tests consecutively performed in Moleculera Labs' clinical laboratory from April 22, 2013 to December 31, 2016, we identified 206 patients who were prescribed at least one panel prior to and following treatment, and who met the PANDAS/PANS diagnostic criteria. Patient follow-up was performed to collect symptoms and treatment or medical intervention. Of the 206 patients, 58 met the inclusion criteria of providing informed consent/assent and documented pre- and post-treatment symptoms. Clinician and parent-reported symptoms after treatment or medical intervention were categorized as “Improved/Resolved” (n = 34) or “Not-Improved/Worsened” (n = 24). These were analyzed for any association between changes in clinical status and changes in Cunningham panel test results. Clinical assay performance was also evaluated for reproducibility and reliability. ResultsComparison of pre- and post-treatment status revealed that the Cunningham Panel results correlated with changes in patient's neuropsychiatric symptoms. Based upon the change in the number of positive tests, the overall accuracy was 86%, the sensitivity and specificity were 88% and 83% respectively, and the Area Under the Curve (AUC) was 93.4%. When evaluated by changes in autoantibody levels, we observed an overall accuracy of 90%, a sensitivity of 88%, a specificity of 92% and an AUC of 95.7%. Assay reproducibility for the calcium/calmodulin-dependent protein kinase II (CaMKII) revealed a correlation coefficient of 0.90 (p < 1.67 × 10−6) and the ELISA assays demonstrated test-retest reproducibility comparable with other ELISA assays. ConclusionThis study revealed a strong positive association between changes in neuropsychiatric symptoms and changes in the level of anti-neuronal antibodies and antibody-mediated CaMKII human neuronal cell activation. These results suggest there may be clinical utility in monitoring autoantibody levels and stimulatory activity against these five neuronal antigen targets as an aid in the diagnosis and treatment of infection-triggered autoimmune neuropsychiatric disorders. Future prospective studies should examine the feasibility of predicting antimicrobial and immunotherapy responses with the Cunningham Panel.

The atypical cadherin flamingo determines the competence of neurons for activity-dependent fine-scale topography

The topographic projection of afferent terminals into two-dimensional maps is essential for sensory systems to encode the locations of sensory stimuli. In vertebrates, guidance cues are critical for establishing a coarse topographic map, while neuronal activity directs fine-scale topography between adjacent afferent terminals. However, the molecular mechanism underlying activity-dependent fine-scale topography is not well known. Studies in the Drosophila visual system have demonstrated that cell-adhesion molecules direct fine-scale topography, but whether or not these molecules are involved in activity-dependent fine-scale topography remains to be determined. We previously reported that the nociceptors in Drosophila larvae form an activity-dependent fine-scale topographic system. The establishment of this system is instructed by the level of neuronal activity in individual nociceptors. Here, we show that the atypical cadherin Flamingo (Fmi) is required for establishing the nociceptor topographic map. We found that the topographic defect caused by loss of fmi was epistatic to the inhibition of neuronal activity and the overexpression of the activity-regulated gene Trim9. These results suggest that Fmi and neuronal activity interact to regulate fine-scale topography. This study provides a link between neuronal activity and the cell-adhesion molecule in the establishment of fine-scale topography.

Neuronal impact of patient-specific aberrant NRXN1α splicing.

NRXN1 undergoes extensive alternative splicing, and non-recurrent heterozygous deletions in NRXN1 are strongly associated with neuropsychiatric disorders. We establish that human induced pluripotent stem cell (hiPSC)-derived neurons represent well the diversity of NRXN1α alternative splicing observed in the human brain, cataloguing 123 high-confidence in-frame human NRXN1α isoforms. Patient-derived NRXN1+/− hiPSC-neurons show greater than two-fold reduction of half of the wild-type NRXN1α isoforms and express dozens of novel isoforms expressed from the mutant allele. Reduced neuronal activity in patient-derived NRXN1+/− hiPSC-neurons is ameliorated by overexpression of individual control isoforms in a genotype-dependent manner, whereas individual mutant isoforms decrease neuronal activity levels in control hiPSC-neurons. In a genotype-dependent manner, the phenotypic impact of patient-specific NRXN1+/− mutations can occur through a reduction in wild-type NRXN1α isoform levels as well as the presence of mutant NRXN1α isoforms.

Spinal gastrin releasing peptide receptor expressing interneurons are controlled by local phasic and tonic inhibition

Dorsal horn gastrin-releasing peptide receptor (GRPR) neurons have a central role in itch transmission. Itch signaling has been suggested to be controlled by an inhibitory network in the spinal dorsal horn, as increased scratching behavior can be induced by pharmacological disinhibition or ablation of inhibitory interneurons, but the direct influence of the inhibitory tone on the GRPR neurons in the itch pathway have not been explored. Here we have investigated spinal GRPR neurons through in vitro and bioinformatical analysis. Electrophysiological recordings revealed that GRPR neurons receive local spontaneous excitatory inputs transmitted by glutamate and inhibitory inputs by glycine and GABA, which were transmitted either by separate glycinergic and GABAergic synapses or by glycine and GABA co-releasing synapses. Additionally, all GRPR neurons received both glycine- and GABA-induced tonic currents. The findings show a complex inhibitory network, composed of synaptic and tonic currents that gates the excitability of GRPR neurons, which provides direct evidence for the existence of an inhibitory tone controlling spontaneous discharge in an itch-related neuronal network in the spinal cord. Finally, calcium imaging revealed increased levels of neuronal activity in Grpr-Cre neurons upon application of somatostatin, which provides direct in vitro evidence for disinhibition of these dorsal horn interneurons.

RNF34 overexpression exacerbates neurological deficits and brain injury in a mouse model of intracerebral hemorrhage by potentiating mitochondrial dysfunction-mediated oxidative stress

Intracerebral hemorrhage (ICH) is a common neurological condition associated with high disability and mortality. Alterations in protein ubiquitination have emerged as a key mechanism in the pathogenesis of neurological diseases. Here, we investigated the effects of the E3 ubiquitin ligase ring finger protein 34 (RNF34) on neurological deficits and brain injury in ICH mice. An ICH model was established via intracerebral injection of autologous blood into wild-type and RNF34 transgenic mice. Brain injury, neurological function, neuronal activity, and oxidative stress levels were measured, respectively. The underlying mechanisms were explored by molecular and cellular approaches. Our results showed that RNF34 overexpression in mice significantly aggravated the ICH-induced memory impairment, brain edema, infarction, hematoma volume, and loss of neuronal activity. RNF34 and oxidative stress levels gradually increased from 6 to 48 h after the ICH challenge and were positively correlated. The ICH-induced increase in intracellular ROS, superoxide anion, and mROS generation and the decrease in adenosine triphosphate production were exacerbated in RNF34 transgenic mice, but NADPH oxidase activity was unaffected. Moreover, RNF34 upregulation potentiated the ICH-induced decrease in PGC-1α, UCP2, and MnSOD expressions. RNF34 interacted with PGC-1α and targeted it for ubiquitin-dependent degradation. This study reveals that RNF34 exacerbates neurological deficits and brain injury by facilitating PGC-1α protein degradation and promoting mitochondrial dysfunction-mediated oxidative stress.

Early lesion of the reticular thalamic nucleus disrupts the structure and function of the mediodorsal thalamus and prefrontal cortex.

The thalamic reticular nucleus (TRN), part of the thalamus, is a thin GABAergic cell layer adjacent to the relay nuclei of the dorsal thalamus. It receives input from the cortex and other thalamic nuclei and provides major inhibitory input to each thalamic nucleus, particularly the mediodorsal nucleus (MD). As the MD is important for supporting optimal cortico-thalamo-cortical interactions during brain maturation, we hypothesized that that early damage to the TRN will cause major disturbances to the development and the functioning of the prefrontal cortex (PFC) and the MD. Rat pups at P4 were randomized in three groups: electrolytic lesion of TRN, TRN-sham-lesion group, and the classical control group. Seven weeks later, all rats were tested with several behavioral and cognitive paradigms, and then perfused for histological and immunohistochemical studies. Results showed that TRN lesion rats exhibited reduced spontaneous activity, high level of anxiety, learning and recognition memory impairments. Besides the behavioral effects observed after early TRN lesions, our study showed significant cytoarchitectural and functional changes in the cingulate cortex, the dorsolateral and prelimbic subdivisions of the PFC, as well as in the MD. The assessment of the basal levels of neuronal activity revealed a significant reduction of the basal expression of C-Fos levels in the PFC. These experiments, which are the first to highlight the effects of early TRN lesions, provided evidence that early damage of the anterior part of the TRN leads to alterations that may control the development of the thalamocortical-corticothalamic pathways.

Elimination of the four extracellular matrix molecules tenascin-C, tenascin-R, brevican and neurocan alters the ratio of excitatory and inhibitory synapses

The synaptic transmission in the mammalian brain is not limited to the interplay between the pre- and the postsynapse of neurons, but involves also astrocytes as well as extracellular matrix (ECM) molecules. Glycoproteins, proteoglycans and hyaluronic acid of the ECM pervade the pericellular environment and condense to special superstructures termed perineuronal nets (PNN) that surround a subpopulation of CNS neurons. The present study focuses on the analysis of PNNs in a quadruple knockout mouse deficient for the ECM molecules tenascin-C (TnC), tenascin-R (TnR), neurocan and brevican. Here, we analysed the proportion of excitatory and inhibitory synapses and performed electrophysiological recordings of the spontaneous neuronal network activity of hippocampal neurons in vitro. While we found an increase in the number of excitatory synaptic molecules in the quadruple knockout cultures, the number of inhibitory synaptic molecules was significantly reduced. This observation was complemented with an enhancement of the neuronal network activity level. The in vivo analysis of PNNs in the hippocampus of the quadruple knockout mouse revealed a reduction of PNN size and complexity in the CA2 region. In addition, a microarray analysis of the postnatal day (P) 21 hippocampus was performed unravelling an altered gene expression in the quadruple knockout hippocampus.

A dynamical model of the laminar BOLD response

High-resolution functional magnetic resonance imaging (fMRI) using blood oxygenation dependent level-dependent (BOLD) signal is an increasingly popular tool to non-invasively examine neuronal processes at the mesoscopic level. However, as the BOLD signal stems from hemodynamic changes, its temporal and spatial properties do not match those of the underlying neuronal activity. In particular, the laminar BOLD response (LBR), commonly measured with gradient-echo (GE) MRI sequence, is confounded by non-local changes in deoxygenated hemoglobin and cerebral blood volume propagated within intracortical ascending veins, leading to a unidirectional blurring of the neuronal activity distribution towards the cortical surface. Here, we present a new cortical depth-dependent model of the BOLD response based on the principle of mass conservation, which takes the effect of ascending (and pial) veins on the cortical BOLD responses explicitly into account. It can be used to dynamically model cortical depth profiles of the BOLD signal as a function of various baseline- and activity-related physiological parameters for any spatiotemporal distribution of neuronal changes. We demonstrate that the commonly observed spatial increase of LBR is mainly due to baseline blood volume increase towards the surface. In contrast, an occasionally observed local maximum in the LBR (i.e. the so-called “bump”) is mainly due to spatially inhomogeneous neuronal changes rather than locally higher baseline blood volume. In addition, we show that the GE-BOLD signal laminar point-spread functions, representing the signal leakage towards the surface, depend on several physiological parameters and on the level of neuronal activity. Furthermore, even in the case of simultaneous neuronal changes at each depth, inter-laminar delays of LBR transients are present due to the ascending vein. In summary, the model provides a conceptual framework for the biophysical interpretation of common experimental observations in high-resolution fMRI data. In the future, the model will allow for deconvolution of the spatiotemporal hemodynamic bias of the LBR and provide an estimate of the underlying laminar excitatory and inhibitory neuronal activity.

Acute L-DOPA administration reverses changes in firing pattern and low frequency oscillatory activity in the entopeduncular nucleus from long term L-DOPA treated 6-OHDA-lesioned rats

The pathophysiology of Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID) is associated with aberrant neuronal activity and abnormal high levels of oscillatory activity and synchronization in several basal ganglia nuclei and the cortex. Previously, we have shown that the firing activity of neurons in the substantia nigra pars reticulata (SNr) is relevant in dyskinesia and may be driven by subthalamic nucleus (STN) hyperactivity. Conversely, low frequency oscillatory activity and synchronization in these structures seem to be more important in PD because they are not influenced by prolonged L-DOPA administration. The aim of the present study was to assess (through single-unit extracellular recording techniques under urethane anaesthesia) the neuronal activity of the entopeduncular nucleus (EPN) and its relationship with LID and STN hyperactivity, together with the oscillatory activity and synchronization between these nuclei and the cerebral cortex in 6-OHDA-lesioned rats that received long term L-DOPA treatment (or not). Twenty-four hours after the last L-DOPA injection the firing activity of EPN neurons in long term L-DOPA treated 6-OHDA-lesioned rats was more irregular and bursting compared to sham rats, being those alterations partially reversed by the acute challenge of L-DOPA. No correlation between EPN neurons firing activity and abnormal involuntary movements score was found. However, there was a significant correlation between the firing activity parameters of EPN and STN neurons recorded from long term L-DOPA treated 6-OHDA-lesioned rats. Low frequency oscillatory activity and synchronization both within the EPN and with the cerebral cortex were enhanced in 6-OHDA-lesioned animals. These changes were reversed by the acute L-DOPA challenge only in long term L-DOPA treated 6-OHDA-lesioned rats. Altogether, these results obtained from long term L-DOPA treated 6-OHDA-lesioned rats suggest (1) a likely relationship between STN and EPN firing patterns and spiking phases induced by changes after prolonged L-DOPA administration and (2) that the effect of L-DOPA on the firing pattern, low frequency oscillatory activity and synchronization in the EPN may have a relevant role in LID.

Neurocognitive exercise program improves the balance performance in children with ADHD: A follow-up study

That adenosine 5′ triphosphate (ATP) functions as an extracellular signaling molecule has been established since the 1970s. Ubiquitous throughout the body as the principal molecular store of intracellular energy, ATP has a short extracellular half-life and is difficult to measure directly. Extracellular ATP concentrations are dependent both on the rate of cellular release and of enzymatic degradation. Some findings from in vitro studies suggest that extracellular ATP concentrations increase during high levels of neuronal activity and seizure-like events in hippocampal slices. Pharmacological studies suggest that antagonism of ATP-sensitive purinergic receptors can suppress the severity of seizures and block epileptogenesis. Directly measuring extracellular ATP concentrations in the brain, however, has a number of specific challenges, notably, the rapid hydrolysis of ATP and huge gradient between intracellular and extracellular compartments. Two studies using microdialysis found no change in extracellular ATP in the hippocampus of rats during experimentally-induced status epilepticus. One of which demonstrated that ATP increased measurably, only in the presence of ectoATPase inhibitors, with the other study demonstrating increases only during later spontaneous seizures. Current evidence is mixed and seems highly dependent on the model used and method of detection. More sensitive methods of detection with higher spatial resolution, which induce less tissue disruption will be necessary to provide evidence for or against the hypothesis of seizure-induced elevations in extracellular ATP. Here we describe the current hypothesis for ATP release during seizures and its role in epileptogenesis, describe the technical challenges involved and critically examine the current evidence.

Exacerbated effects of prorenin on hypothalamic magnocellular neuronal activity and vasopressin plasma levels during salt-sensitive hypertension.

Accumulating evidence supports that the brain renin-angiotensin system (RAS), including prorenin (PR) and its receptor (PRR), two newly discovered RAS players, contribute to sympathoexcitation in salt-sensitive hypertension. Still, whether PR also contributed to elevated circulating levels of neurohormones such as vasopressin (VP) during salt-sensitive hypertension, and if so, what are the precise underlying mechanisms, remains to be determined. To address these questions, we obtained patch-clamp recordings from hypothalamic magnocellular neurosecretory neurons (MNNs) that synthesize the neurohormones oxytocin and VP in acute hypothalamic slices obtained from sham and deoxycorticosterone acetate (DOCA)-salt-treated hypertensive rats. We found that focal application of PR markedly increased membrane excitability and firing responses in MNNs of DOCA-salt, compared with sham rats. This effect included a shorter latency to spike initiation and increased numbers of spikes in response to depolarizing stimuli and was mediated by a more robust inhibition of A-type K+ channels in DOCA-salt compared with sham rats. On the other hand, the afterhyperpolarizing potential mediated by the activation of Ca2+-dependent K+ channel was not affected by PR. mRNA expression of PRR, VP, and the Kv4.3 K+ channel subunit in the supraoptic nucleus of DOCA-salt hypertensive rats was increased compared with sham rats. Finally, we report a significant decrease of plasma VP levels in neuron-selective PRR knockdown mice treated with DOCA-salt, compared with wild-type DOCA-salt-treated mice. Together, these results support that activation of PRR contributes to increased excitability and firing discharge of MNNs and increased plasma levels of VP in DOCA-salt hypertension.NEW & NOTEWORTHY Our studies support that prorenin (PR) and its receptor (PRR) within the hypothalamus contribute to elevated plasma vasopressin levels in deoxycorticosterone acetate-salt hypertension, in part because of an exacerbated effect of PR on magnocellular neurosecretory neuron excitability; Moreover, our study implicates A-type K+ channels as key underlying molecular targets mediating these effects. Thus, PR/PRR stands as a novel therapeutic target for the treatment of neurohumoral activation in salt-sensitive hypertension.

Axoglial interactions in myelin plasticity: Evaluating the relationship between neuronal activity and oligodendrocyte dynamics.

Myelin is a critical component of the vertebrate nervous system, both increasing the conduction velocity of myelinated axons and allowing for metabolic coupling between the myelinating cells and axons. An increasing number of studies demonstrate that myelination is not simply a developmentally hardwired program, but rather that new myelinating oligodendrocytes can be generated throughout life. The generation of these oligodendrocytes and the formation of myelin are influenced both during development and adulthood by experience and levels of neuronal activity. This led to the concept of adaptive myelination, where ongoing activity-dependent changes to myelin represent a form of neural plasticity, refining neuronal functioning, and circuitry. Although human neuroimaging experiments support the concept of dynamic changes within specific white matter tracts relevant to individual tasks, animal studies have only just begun to probe the extent to which neuronal activity may alter myelination at the level of individual circuits and axons. Uncovering the role of adaptive myelination requires a detailed understanding of the localized interactions that occur between active axons and myelinating cells. In this review, we focus on recent animal studies that have begun to investigate the interactions between active axons and myelinating cells and review the evidence for-and against-the ability of neuronal activity to alter myelination at an axon-specific level.

Probiotic treatment restores normal developmental trajectories of fear memory retention in maternally separated infant rats

Early life stress (ELS) can affect brain development and increase lifetime prevalence of psychiatric illnesses. However, the effective therapeutic interventions to ameliorate the deleterious effects of ELS have not yet been well established. Here, we confirmed that maternal separation (MS) for 3 h daily between postnatal days 2–14, a frequently used experimental model of ELS, resulted in early expression of adult-like fear memory retention in male infant rats. Administration of a probiotic formulation, Lacidofil® (95% Lactobacillus rhamnosus R0011 and 5% Lactobacillus helveticus R0052), during the separation period, prevented the precocious transition to adult-like fear memory retention in MS infant rats. Consonant with this effect, probiotic treatment also ameliorated the MS-induced increases in anxiety-like behavior as measured by the elevated plus maze and the light-dark box tests. In addition, probiotic treatment reduced MS-induced increases in neuronal activation and brain-derived neurotrophic factor protein levels in the basolateral nucleus of amygdala (BLA) after auditory fear conditioning. Furthermore, we found that probiotic treatment significantly rescued the heightened hypothalamic-pituitary-adrenal (HPA) axis response to restraint stress in MS infant rats. Taken together, these findings suggest that probiotics can restore normal developmental trajectories of fear memory retention in MS infant rats, at least in part by normalizing HPA axis abnormalities, and that the BLA serves as a critical node to mediate these interventions. Thus, we offer a potential therapeutic intervention to protect children against the harmful effects of ELS.

Glutamate diffusion in the rat brain in vivo under light and deep anesthesia conditions.

Glutamate (Glu) is the most abundant neurotransmitter in the human central nervous system and glutamatergic neurotransmission has been implicated in many common and severe neuropsychiatric disorders. In vivo MRS techniques have been developed to measure brain Glu concentration to investigate the pathophysiology of various brain disorders. However, it is difficult to interpret Glu signal changes because Glu plays multiple roles in the brain and is found in multiple microenvironments including cytosolic, vesicular, and extracellular. In vivo diffusion-weighted MRS (DW-MRS) with low to very high b-values was performed on the rat prefrontal cortex at 9.4T under both light and deep anesthetic conditions to examine Glu diffusion properties. Significant alterations in Glu diffusion as well as reduced Glu concentration were observed under deep anesthesia compared with superficial anesthesia in the absence of similar changes in NAA or creatine. The modifications in Glu diffusion under deep anesthesia might reflect changes in Glu microenvironment. The present work shows that Glu DW-MRS could be an important tool to explore Glu physiology with changing levels of neuronal activity and synaptic function.

Voltage-gated sodium channels from the bees Apis mellifera and Bombus terrestris are differentially modulated by pyrethroid insecticides

Recent experimental and in-field evidence of the deleterious effects of insecticides on the domestic honey bee Apis mellifera have led to a tightening of the risk assessment requirements of these products, and now more attention is being paid to their sublethal effects on other bee species. In addition to traditional tests, in vitro and in silico approaches may become essential tools for a comprehensive understanding of the impact of insecticides on bee species. Here we present a study in which electrophysiology and a Markovian multi-state modelling of the voltage-gated sodium channel were used to measure the susceptibility of the antennal lobe neurons from Apis mellifera and Bombus terrestris, to the pyrethroids tetramethrin and esfenvalerate. Voltage-gated sodium channels from Apis mellifera and Bombus terrestris are differentially sensitive to pyrethroids. In both bee species, the level of neuronal activity played an important role in their relative sensitivity to pyrethroids. This work supports the notion that honey bees cannot unequivocally be considered as a surrogate for other bee species in assessing their neuronal susceptibility to insecticides.

Maladaptive cortical hyperactivity upon recovery from experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) patients exhibit neuropsychological symptoms in early disease despite the immune attack occurring predominantly in white matter and spinal cord. It is unclear why neurodegeneration may start early in the disease and is prominent in later stages. We assessed cortical microcircuit activity by employing spiking-specific two-photon Ca2+ imaging in proteolipid protein-immunized relapsing-remitting SJL/J mice in vivo. We identified the emergence of hyperactive cortical neurons in remission only, independent of direct immune-mediated damage and paralleled by elevated anxiety. High levels of neuronal activity were accompanied by increased caspase-3 expression. Cortical TNFα expression was mainly increased by excitatory neurons in remission; blockade with intraventricular infliximab restored AMPA spontaneous excitatory postsynaptic current frequencies, completely recovered normal neuronal network activity patterns and alleviated elevated anxiety. This suggests a dysregulation of cortical networks attempting to achieve functional compensation by synaptic plasticity mechanisms, indicating a link between immune attack and early start of neurodegeneration.

Functional Neuroimaging: Single Photon Emission Computed Tomography (SPECT) In Neurological Disorders

A single photon emission computed tomography (SPECT) scan is a functional nuclear imaging technique performed to evaluate regional cerebral perfusion. Because cerebral blood flow is closely linked to neuronal activity, the activity distribution is presumed to reflect neuronal activity levels in several areas of the brain. Although structural magnetic resonance imaging (MRI) and computed tomography (CT) provide exquisite anatomical detail, SPECT provide complementary functional information. Frequently, brain pathology will manifest as functional changes before anatomical changes are detectable. SPECT has clinical value in the diagnosis, therapeutic management, and follow-up of patients. A general consideration of the clinical value of this technique is followed by relevant information on cerebral physiology and pathology for proper understanding of brain SPECT images. The diversity of central nervous system diseases and therefore the still incomplete knowledge of the mechanisms that underlie them have contributed to the success of brain perfusion SPECT as a research tool in neurosciences. Finally, stepby- step recommendations for interpreting and reporting brain perfusion SPECT images are provided to get the utmost clinical beneût from this technique. Bangladesh Journal of Neuroscience 2018; Vol. 34 (2): 96-105