Large Neurons Research Articles

THE CYTOARCHITECTONICS AND NEURONAL ORGANIZATION OF THE BASOLATERAL NUCLEUS OF THE AMYGDALA OF THE BRAIN IN ALCOHOL-PREFERRING AND ALCOHOL-NONPREFERRING RATS

Analysis of cytoarchitectonics of the basolateral nucleus (BLN) of the brain amygdala was performed in cresyl violet-stained frontal paraffin sections of the brain in 10 alcohol-preferring (AP) and 10 alcohol-nonpreferring (ANP) rats (with an equal number of male and female animals in each group). The presence of large and small neurons was detected in BLN. Most of the large neurons in AP rats had the character of chromoneutral and moderately chromophilic cells, while in ANP rats these cells were moderately chromophobic. Application of Golgi method demonstrated that the equivalents of large neurons were long-axonal densely branched pyramid-like neurons, and those of small-sized neurons - short-axonal neurons. The determination of the ratio of large and small-sized neurons showed that in AP rats the proportion of latter was 12.3±0.6%, while in the ANP rats it was significantly greater - 19.70±0.23%. These results help to explain the previously obtained data on larger specific area of BLN in amygdala of ANP rats by the presence of greater number of interneurons than in AP rats.

Lentivirus-meditated frataxin gene delivery reverses genome instability in Friedreich ataxia patient and mouse model fibroblasts.

Friedreich ataxia (FRDA) is a progressive neurodegenerative disease caused by deficiency of frataxin protein, with the primary sites of pathology being the large sensory neurons of the dorsal root ganglia and the cerebellum. FRDA is also often accompanied by severe cardiomyopathy and diabetes mellitus. Frataxin is important in mitochondrial iron–sulfur cluster (ISC) biogenesis and low-frataxin expression is due to a GAA repeat expansion in intron 1 of the FXN gene. FRDA cells are genomically unstable, with increased levels of reactive oxygen species and sensitivity to oxidative stress. Here we report the identification of elevated levels of DNA double strand breaks (DSBs) in FRDA patient and YG8sR FRDA mouse model fibroblasts compared to normal fibroblasts. Using lentivirus FXN gene delivery to FRDA patient and YG8sR cells, we obtained long-term overexpression of FXN mRNA and frataxin protein levels with reduced DSB levels towards normal. Furthermore, γ-irradiation of FRDA patient and YG8sR cells revealed impaired DSB repair that was recovered on FXN gene transfer. This suggests that frataxin may be involved in DSB repair, either directly by an unknown mechanism, or indirectly via ISC biogenesis for DNA repair enzymes, which may be essential for the prevention of neurodegeneration.

Widening Spectrum of Cellular and Subcellular Expression of Human GLUD1 and GLUD2 Glutamate Dehydrogenases Suggests Novel Functions.

Mammalian glutamate dehydrogenase1 (GDH1) (E.C. 1.4.1.3) is a mitochondrial enzyme that catalyzes the reversible oxidative deamination of glutamate to α-ketoglutarate and ammonia while reducing NAD+ and/or NADP+ to NADH and/or NADPH. It links amino acid with carbohydrate metabolism, contributing to Krebs cycle anaplerosis, energy production, ammonia handling and redox homeostasis. Although GDH1 was one of the first major metabolic enzymes to be studied decades ago, its role in cell biology is still incompletely understood. There is however growing interest in a novel GDH2 isoenzyme that emerged via duplication in primates and underwent rapid evolutionary selection concomitant with prefrontal human cortex expansion. Also, the anaplerotic function of GDH1 and GDH2 is currently under sharp focus as this relates to the biology of glial tumors and other neoplasias. Here we used antibodies specific for human GDH1 (hGDH1) and human GDH2 (hGDH2) to study the expression of these isoenzymes in human tissues. Results revealed that both hGDH1 and hGDH2 are expressed in human brain, kidney, testis and steroidogenic organs. However, distinct hGDH1 and hGDH2 expression patterns emerged. Thus, while the Sertoli cells of human testis were strongly positive for hGDH2, they were negative for hGDH1. Conversely, hGDH1 showed very high levels of expression in human liver, but hepatocytes were virtually devoid of hGDH2. In human adrenals, both hGDHs were densely expressed in steroid-producing cells, with hGDH2 expression pattern matching that of the cholesterol side chain cleavage system involved in steroid synthesis. Similarly in human ovaries and placenta, both hGDH1 and hGDH2 were densely expressed in estrogen producing cells. In addition, hGDH1, being a housekeeping enzyme, was also expressed in cells that lack endocrine function. Regarding human brain, study of cortical sections using immunofluorescence (IF) with confocal microscopy revealed that hGDH1 and hGDH2 were both expressed in the cytoplasm of gray and white matter astrocytes within coarse structures resembling mitochondria. Additionally, hGDH1 localized to the nuclear membrane of a subpopulation of astrocytes and of the vast majority of oligodendrocytes and their precursors. Remarkably, hGDH2-specific staining was detected in human cortical neurons, with different expression patterns having emerged. One pattern, observed in large cortical neurons (some with pyramidal morphology), was a hGDH2-specific labeling of cytoplasmic structures resembling mitochondria. These were distributed either in the cell body-axon or on the cell surface in close proximity to astrocytic end-feet that encircle glutamatergic synapses. Another pattern was observed in small cortical neurons with round dense nuclei in which the hGDH2-specific staining was found in the nuclear membrane. A detailed description of these observations and their functional implications, suggesting that the GDH flux is used by different cells to serve some of their unique functions, is presented below.

Minute amounts of hamartin wildtype rescue the emergence of tuber-like lesions in conditional Tsc1 ablated mice

Tuberous sclerosis (TSC) is a phacomatosis associated with highly differentiated malformations including tubers in the brain. Those are composed of large dysplastic neurons and ‘giant cells’. Cortical tubers are frequent causes of chronic seizures and resemble neuropathologically focal cortical dysplasias (FCD) type IIb. Patients with FCDIIb, however, lack additional stigmata of TSC. Mutations and allelic variants of the TSC1 gene have been observed in patients with tubers as well as FCDIIb. Those include hamartinR692X and hamartinR786X, stop mutants frequent in TSC patients and hamartinH732Y frequent in FCDIIb. Expression of these variants in cell culture led to aberrant distribution of corresponding proteins. We here scrutinized morphological and structural effects of these TSC1 variants by intraventricular in utero electroporation (IUE), genetically mimicking the discrete focal character and a somatic postzygotic mosaicism of the lesion, focusing on the gene dosage required for tuber-like lesions to emerge in Tsc1flox/flox mice. Expression of only hamartinR692X as well as hamartinR786X led to a 2-fold enlargement of neurons with high pS6 immunoreactivity, stressing their in vivo pathogenic potential. Co-electroporation of the different aberrant alleles and varying amounts of wildtype TSC1 surprisingly revealed already minimal amounts of functional hamartin to be sufficient for phenotype rescue. This result strongly calls for further studies to unravel new mechanisms for substantial silencing of the second allele in cortical tubers, as proposed by Knudson's ‘2-hit hypothesis’. The rescuing effects may provide a promising basis for gene therapies aiming at reconstituting hamartin expression in tubers.

Cerebral glucose hypometabolism in Tick-Borne Encephalitis, a pilot study in 10 Patients

BackgroundTick borne encephalitis (TBE) is an acute meningoencephalitis with or without myelitis caused by an RNA virus from the flavivirus family transmitted by Ixodes spp ticks. The neurotropic TBE virus infects preferentially large neurons in basal ganglia, anterior horns, medulla oblongata, Purkinje cells and thalamus. Brain metabolic changes related to radiologic and clinical findings have not been described so far. MethodsHere we describe the clinical course of 10 consecutive TBE patients with outcome assessment at discharge and after 12 month using a modified Rankin Scale. Patients underwent cerebral MRI after confirmation of diagnosis and before discharge. 18F-FDG PET/CT scans were performed within day 5 to day 14 after TBE diagnosis. Extended analysis of coagulation parameters by thrombelastometry (ROTEM® InTEM, ExTEM, FibTEM) was performed every other day after confirmation of TBE diagnosis up to day 10 after hospital admission or discharge. ResultsAll patients presented with a meningoencephalitic course of disease. Cerebral MRI scans showed unspecific findings at predilection areas in 3 patients. 18F-FDG PET/CT showed increased glucose utilization in one patient and decreased 18F-FDG uptake in seven patients. Changes in coagulation measured by standard parameters and thrombelastometry were not found in any of the patients. DiscussionGlucose hypometabolism was present in 7 out of 10 TBE patients reflecting neuronal dysfunction in predilection areas of TBE virus infiltration responsible for development of clinical signs and symptoms.

The number of striatal cholinergic interneurons expressing calretinin is increased in parkinsonian monkeys

The most abundant interneurons in the primate striatum are those expressing the calcium-binding protein calretinin (CR). The present immunohistochemical study provides detailed assessments of their morphological traits, number, and topographical distribution in normal monkeys (Macaca fascicularis) and in monkeys rendered parkinsonian (PD) by MPTP intoxication. In primates, the CR+ striatal interneurons comprise small (8–12μm), medium (12–20μm) and large-sized (20–45μm) neurons, each with distinctive morphologies. The small CR+ neurons were 2–3 times more abundant than the medium-sized CR+ neurons, which were 20–40 times more numerous than the large CR+ neurons. In normal and PD monkeys, the density of small and medium-sized CR+ neurons was twice as high in the caudate nucleus than in the putamen, whereas the inverse occurred for the large CR+ neurons. Double immunostaining experiments revealed that only the large-sized CR+ neurons expressed choline acetyltransferase (ChAT). The number of large CR+ neurons was found to increase markedly (4–12 times) along the entire anteroposterior extent of both the caudate nucleus and putamen of PD monkeys compared to controls. Comparison of the number of large CR−/ChAT+ and CR+/ChAT+ neurons together with experiments involving the use of bromo-deoxyuridine (BrdU) as a marker of newly generated cells showed that it is the expression of CR by the large ChAT+ striatal interneurons, and not their absolute number, that is increased in the dopamine-depleted striatum. These findings reveal the modulatory role of dopamine in the phenotypic expression of the large cholinergic striatal neurons, which are known to play a crucial role in PD pathophysiology.

Effects of Exogenous NUB1 Expression in the Striatum of HDQ175/Q7 Mice.

Reducing mutant huntingtin (mHTT) in neurons may be a therapy for Huntington's disease (HD). Elevating NUB1 protein reduced mHTT levels in cell and fly models of HD through a proteasome dependent mechanism. To examine the effects of augmenting NUB1 in HD mouse striatum on mHTT levels. Striata of HDQ175/Q7 mice were injected at 3 months of age with recombinant AAV2/9 coding for NUB1 or GFP under the control of the neuron specific human synapsin 1 promoter and examined 6 months post-injection for levels of huntingtin, the striatal markers DARPP32 and PDE10A, the astrocyte marker GFAP, and the autophagy and mHTT aggregate marker P62 using immunolabeling of brain sections and Western blot assay of striatal subcellular fractions. By Western blot human HD brain had only one of the two variants of NUB1 present in human control brain. In striatum of WT and HD mice NUB1 was localized in medium size neurons and enriched in the nucleus of large neurons. In the striatum of NUB1 injected HD mice, there was widespread neuronal distribution of exogenous NUB1 labeling and protein levels were ∼2.5-fold endogenous levels. DARPP32 and GFAP distribution and levels were unchanged but PDE10A levels were lower in crude homogenates and P62 was increased in nuclear enriched P1 fractions. Elevating NUB1 did not change levels of full-length mHTT or the number and size of mHTT (S830) positive nuclear inclusions. Findings suggest that increasing NUB1 protein in striatal neurons of HDQ175/Q7 mice in vivo may be relatively safe but is ineffective in reducing mHTT. Increased NUB1 expression in HD striatum alters PDE10A and P62 which are known to be influenced by mHTT.

Mechanisms, pools, and sites of spontaneous vesicle release at synapses of rod and cone photoreceptors.

Photoreceptors have depolarized resting potentials that stimulate calcium-dependent release continuously from a large vesicle pool but neurons can also release vesicles without stimulation. We characterized the Ca(2+) dependence, vesicle pools, and release sites involved in spontaneous release at photoreceptor ribbon synapses. In whole-cell recordings from light-adapted horizontal cells (HCs) of tiger salamander retina, we detected miniature excitatory post-synaptic currents (mEPSCs) when no stimulation was applied to promote exocytosis. Blocking Ca(2+) influx by lowering extracellular Ca(2+) , by application of Cd(2+) and other agents reduced the frequency of mEPSCs but did not eliminate them, indicating that mEPSCs can occur independently of Ca(2+) . We also measured release presynaptically from rods and cones by examining quantal glutamate transporter anion currents. Presynaptic quantal event frequency was reduced by Cd(2+) or by increased intracellular Ca(2+) buffering in rods, but not in cones, that were voltage clamped at -70mV. By inhibiting the vesicle cycle with bafilomycin, we found the frequency of mEPSCs declined more rapidly than the amplitude of evoked excitatory post-synaptic currents (EPSCs) suggesting a possible separation between vesicle pools in evoked and spontaneous exocytosis. We mapped sites of Ca(2+) -independent release using total internal reflectance fluorescence (TIRF) microscopy to visualize fusion of individual vesicles loaded with dextran-conjugated pHrodo. Spontaneous release in rods occurred more frequently at non-ribbon sites than evoked release events. The function of Ca(2+) -independent spontaneous release at continuously active photoreceptor synapses remains unclear, but the low frequency of spontaneous quanta limits their impact on noise.

Monoclonal antibody Py recognizes neurofilament heavy chain and is a selective marker for large diameter neurons in the brain.

Almost 30years ago, the monoclonal antibody Py was developed to detect pyramidal neurons in the CA3 region of the rat hippocampus. The utility of this antibody quickly expanded when several groups discovered that it could be used to identify very specific populations of neurons in the normal, developing, and diseased or injured central nervous system. Despite this body of literature, the identity of the antigen that the Py antibody recognizes remained elusive. Here, immunoprecipitation experiments from the adult rat cortex identified the Py antigen as neurofilament heavy chain (NF-H). Double immunolabeling of sections through the rat brain using Py and NF-H antibodies confirmed the identity of the Py antigen, and reveal that Py/NF-H+ neurons appear to share the feature of being particularly large in diameter. These include the neurons of the gigantocellular reticular formation, pyramidal neurons of layers II/III and V of the cortex, cerebellar Purkinje neurons as well as CA3 pyramidal neurons. Taken together, this finding gives clarity to past work using the monoclonal Py antibody, and immediately expands our understanding of the importance of NF-H in neural development, functioning, and disease.

Metric hashing forests

In this paper, we propose metric Hashing Forests (mHF) which is a supervised variant of random forests tailored for the task of nearest neighbor retrieval through hashing. This is achieved by training independent hashing trees that parse and encode the feature space such that local class neighborhoods are preserved and encoded with similar compact binary codes. At the level of each internal node, locality preserving projections are employed to project data to a latent subspace, where separability between dissimilar points is enhanced. Following which, we define an oblique split that maximally preserves this separability and facilitates defining local neighborhoods of similar points. By incorporating the inverse-lookup search scheme within the mHF, we can then effectively mitigate pairwise neuron similarity comparisons, which allows for scalability to massive databases with little additional time overhead. Exhaustive experimental validations on 22,265 neurons curated from over 120 different archives demonstrate the superior efficacy of mHF in terms of its retrieval performance and precision of classification in contrast to state-of-the-art hashing and metric learning based methods. We conclude that the proposed method can be utilized effectively for similarity-preserving retrieval and categorization in large neuron databases.

The effects of incubation temperature on the development of the cortical forebrain in a lizard.

The embryos of egg-laying species are exposed to variable thermal regimes, which can influence not only the resultant hatchling's morphology (e.g., size, sex) and performance (e.g., locomotor speed), but also its cognitive performance (learning ability). To clarify the proximate basis for this latter effect, we incubated eggs of the scincid lizard Bassiana duperreyi under simulated 'hot' and 'cold' natural nest temperatures to examine the effect of incubation temperature on the structure of the telencephalon region of the forebrain. Hatchlings from low-temperature incubation had larger telencephalons (both in absolute terms and relative to body size) and larger neurons in their medial cortices, whereas the medial cortices of hatchlings from high-temperature incubation had fewer neurons overall, but greater neuronal density, and more neurons in certain areas. These temperature-induced differences in B. duperreyi forebrain development are consistent with (and may explain) the disparities in learning ability between hatchlings from our two incubation treatments. The phenotypic plasticity of lizard telencephalon anatomy in response to incubation temperature presents exciting opportunities for studies on the evolutionary and developmental determinants of intelligence in vertebrates, but also offers a cautionary tale. Global climate changes, wrought by anthropogenic activities, may directly modify brain structure in reptiles.

Magnetoreception Regulates Male Courtship Activity in Drosophila.

The possible neurological and biophysical effects of magnetic fields on animals is an area of active study. Here, we report that courtship activity of male Drosophila increases in a magnetic field and that this effect is regulated by the blue light-dependent photoreceptor cryptochrome (CRY). Naïve male flies exhibited significantly increased courtship activities when they were exposed to a ≥ 20-Gauss static magnetic field, compared with their behavior in the natural environment (0 Gauss). CRY-deficient flies, cryb and crym, did not show an increased courtship index in a magnetic field. RNAi-mediated knockdown of cry in cry-GAL4-positive neurons disrupted the increased male courtship activity in a magnetic field. Genetically expressing cry under the control of cry-GAL4 in the CRY-deficient flies restored the increase in male courtship index that occurred in a magnetic field. Interestingly, artificially activating cry-GAL4-expressing neurons, which include large ventral lateral neurons and small ventral lateral neurons, via expression of thermosensitive cation channel dTrpA1, also increased the male courtship index. This enhancement was abolished by the addition of the cry-GAL80 transgene. Our results highlight the phenomenon of increased male courtship activity caused by a magnetic field through CRY-dependent magnetic sensation in CRY expression neurons in Drosophila.

Development and Characterization of a Macaque Model of Focal Internal Capsular Infarcts

Several studies have used macaque monkeys with lesions induced in the primary motor cortex (M1) to investigate the recovery of motor function after brain damage. However, in human stroke patients, the severity and outcome of motor impairments depend on the degree of damage to the white matter, especially that in the posterior internal capsule, which carries corticospinal tracts. To bridge the gap between results obtained in M1-lesioned macaques and the development of clinical intervention strategies, we established a method of inducing focal infarcts at the posterior internal capsule of macaque monkeys by injecting endothelin-1 (ET-1), a vasoconstrictor peptide. The infarcts expanded between 3 days and 1 week after ET-1 injection. The infarct volume in each macaque was negatively correlated with precision grip performance 3 days and 1 week after injection, suggesting that the degree of infarct expansion may have been a cause of the impairment in hand movements during the early stage. Although the infarct volume decreased and gross movement improved, impairment of dexterous hand movements remained until the end of the behavioral and imaging experiments at 3 months after ET-1 injection. A decrease in the abundance of large neurons in M1, from which the descending motor tracts originate, was associated with this later-stage impairment. The present model is useful not only for studying neurological changes underlying deficits and recovery but also for testing therapeutic interventions after white matter infarcts in primates.

Nociceptin/orphanin FQ receptor expression in clinical pain disorders and functional effects in cultured neurons.

The nociceptin/orphanin FQ peptide receptor (NOP), activated by its endogenous peptide ligand nociceptin/orphanin FQ (N/OFQ), exerts several effects including modulation of pain signalling. We have examined, for the first time, the tissue distribution of the NOP receptor in clinical visceral and somatic pain disorders by immunohistochemistry and assessed functional effects of NOP and μ-opioid receptor activation in cultured human and rat dorsal root ganglion (DRG) neurons. Quantification of NOP-positive nerve fibres within the bladder suburothelium revealed a remarkable several-fold increase in detrusor overactivity (P < 0.0001) and painful bladder syndrome patient specimens (P = 0.0014) compared with controls. In postmortem control human DRG, 75% to 80% of small/medium neurons (≤50 μm diameter) in the lumbar (somatic) and sacral (visceral) DRG were positive for NOP, and fewer large neurons; avulsion-injured cervical human DRG neurons showed similar numbers. NOP immunoreactivity was significantly decreased in injured peripheral nerves (P = 0.0004), and also in painful neuromas (P = 0.025). Calcium-imaging studies in cultured rat DRG neurons demonstrated dose-dependent inhibition of capsaicin responses in the presence of N/OFQ, with an IC50 of 8.6 pM. In cultured human DRG neurons, 32% inhibition of capsaicin responses was observed in the presence of 1 pM N/OFQ (P < 0.001). The maximum inhibition of capsaicin responses was greater with N/OFQ than μ-opioid receptor agonist DAMGO. Our findings highlight the potential of NOP agonists, particularly in urinary bladder overactivity and pain syndromes. The regulation of NOP expression in visceral and somatic sensory neurons by target-derived neurotrophic factors deserves further study, and the efficacy of NOP selective agonists in clinical trials.

Structure and Function of Dragonfly Looming‐Sensitive Neurons

In this project, I aim to identify specific neurons in the dragonfly brain that respond selectively to looming stimuli. In the dragonfly nerve cord, there are large visual neurons, called Target Selective Descending Neurons (TSDNs). These neurons respond selectively to small moving stimuli, which mimic the movements of dragonfly prey. The response of these neurons is the steering movement of the dragonfly's wings, allowing them to predict the location of their prey for accurate interception. A subset of the TSDNs show large and precisely timed responses to the expanding image of an approaching object. I will be studying these “looming‐sensitive” neurons, researching what visual information they are sending to the flight system. This material will allow for the analysis of the anatomical structure in the dragonfly brain. The visual responses of these dragonflies suggests that the looming‐sensitive neurons are the specific TSDNs called MDT3 and DIT3, but in order to confirm this prediction, we must visualize the anatomy of the brain. With the use of a dye called Lucifer yellow, we can trace the response of the looming stimuli to a specific area of the brain. By injecting the dye with a recording microelectrode, we can positively identify these specific neurons.Support or Funding InformationUnion College Undergraduate Research Committee

Immunolocalization of gaseous neurotransmitters in interneurons in the medulla oblongata in rats

We studied groups of internuclear interneurons (IN) that are located between the magnocellular and parvocellular reticular nuclei (IN1), reticular parvocellular nucleus, the nucleus of the solitary tract (IN2), and around the reticular lateral nucleus (IN3) that express the neuronal NO-synthase, cystathionine s-synthase, or heme oxygenase-2 in the medulla oblongata of Wistar rats using histochemical and immunohistochemical methods. We found local differences in the organization of INs. These differences were evident between IN1 cells, a cell group that consists of a relatively large number of large neurons, including giant cells, and IN2–IN3 cells. In interneurons of the latter two IN groups, we found significantly higher concentrations of cells and intensity of immunohistochemical staining. The local differences between the cells that contain cystathionine s-synthase were less pronounced than between other gaseous neurotransmitter interneurons. These data indicate that the internuclear interneurons have the structure that is necessary for the successful management of integration processes in the brain.

The Drosophila Receptor Protein Tyrosine Phosphatase LAR Is Required for Development of Circadian Pacemaker Neuron Processes That Support Rhythmic Activity in Constant Darkness But Not during Light/Dark Cycles.

In animals, circadian clocks drive daily rhythms in physiology, metabolism, and behavior via transcriptional feedback loops. Because key circadian transcriptional activators and repressors are regulated by phosphorylation, we screened for phosphatases that alter activity rhythms when their expression was reduced. One such phosphatase, leukocyte-antigen-related (LAR), abolishes activity rhythms, but does not disrupt feedback loop function. Rather,Lardisrupts clock output by eliminating axonal processes from clock neurons that release pigment-dispersing factor (PDF) neuropeptide into the dorsal brain, but PDF expression persists in their cell bodies and remaining projections. In contrast to flies that lack PDF, flies that lackLaranticipate lights-on and lights-off transitions normally, which suggests that the remaining PDF expression mediates activity during light/dark cycles.

Inflammatory cytokines influence measures of white matter integrity in bipolar disorder

Midcingulate cortex (MCC) has risen in prominence as human imaging identifies unique structural and functional activity therein and this is the first review of its structure, connections, functions and disease vulnerabilities. The MCC has two divisions (anterior, aMCC and posterior, pMCC) that represent functional units and the cytoarchitecture, connections and neurocytology of each is shown with immunohistochemistry and receptor binding. The MCC is not a division of anterior cingulate cortex (ACC) and the “dorsal ACC” designation is a misnomer as it incorrectly implies that MCC is a division of ACC. Interpretation of findings among species and developing models of human diseases requires detailed comparative studies which is shown here for five species with flat maps and immunohistochemistry (human, monkey, rabbit, rat, mouse). The largest neurons in human cingulate cortex are in layer Vb of area 24 d in pMCC which project to the spinal cord. This area is part of the caudal cingulate premotor area which is involved in multisensory orientation of the head and body in space and neuron responses are tuned for the force and direction of movement. In contrast, the rostral cingulate premotor area in aMCC is involved in action-reinforcement associations and selection based on the amount of reward or aversive properties of a potential movement. The aMCC is activated by nociceptive information from the midline, mediodorsal and intralaminar thalamic nuclei which evoke fear and mediates nocifensive behaviors. This subregion also has high dopaminergic afferents and high dopamine-1 receptor binding and is engaged in reward processes. Opposing pain/avoidance and reward/approach functions are selected by assessment of potential outcomes and error detection according to feedback-mediated, decision making. Parietal afferents differentially terminate in MCC and provide for multisensory control in an eye- and head-centric manner. Finally, MCC vulnerability in human disease confirms the unique organization of MCC and supports the predictive validity of the MCC dichotomy. Vulnerability of aMCC is shown in chronic pain, obsessive-compulsive disorder with checking symptoms and attention-deficit/hyperactivity disorder and methylphenidate and pain medications selectively impact aMCC. In contrast, pMCC vulnerabilities are for progressive supranuclear palsy, unipolar depression and posttraumatic stress disorder. Thus, there is an emerging picture of the organization, functions and diseases of MCC. Future work will take this type of modular analysis to individual areas of which there are at least 10 in MCC.

Sex and laterality differences in medial amygdala neurons and astrocytes of adult mice.

The posterodorsal aspect of the medial amygdala (MePD) in rats is sexually dimorphic, being larger and containing more and larger neurons in males than in females. It is also highly lateralized, with the right MePD larger than the left in both sexes, but with the smaller left MePD actually containing more and larger neurons than the larger right. Astrocytes are also strikingly sexually differentiated, with male-biased numbers and lateralized favoring the right in the rat MePD. However, comparable information is scant for mice where genetic tools offer greater experimental power. Hence, we examined the MePD from adult male and female C57Bl/6(J) mice. We now report that the MePD is larger in males than in females, with the MePD in males containing more astrocytes and neurons than in females. However, we did not find sex differences in astrocyte complexity or overall glial number nor effects of laterality in either measure. While the mouse MePD is generally less lateralized than in rats, we did find that the sex difference in astrocyte number is only on the right because of a significant lateralization in females, with significantly fewer astrocytes on the right than the left but only in females. A sex difference in neuronal soma size favoring males was also evident, but only on the left. Sex differences in the number of neurons and astrocytes common to both rodent species may represent core morphological features that critically underlie the expression of sex-specific behaviors that depend on the MePD. J. Comp. Neurol. 524:2492-2502, 2016. © 2016 Wiley Periodicals, Inc.

Frequency-selective transmission of graded signals in large monopolar neurons of blowfly Calliphora vicina compound eye.

The functional roles of voltage-gated K(+)(Kv) channels in visual system interneurons remain poorly studied. We have addressed this problem in the large monopolar cells (LMCs) of the blowfly Calliphora vicina, using intracellular recordings and mathematical modeling methods. Intracellular recordings were performed in two cellular compartments: the synaptic zone, which receives input from photoreceptors, and the axon, which provides graded potential output to the third-order visual neurons. Biophysical properties of Kv conductances in the physiological voltage range were examined in the dark with injections of current in the discontinuous current-clamp mode. Putative LMC types 1/2 and 3 (L1/2 and L3, respectively) had dissimilar Kv channelomes: L1/2 displayed a prominent inactivating Kv conductance in the axon, while L3 cells were characterized by a sustained delayed-rectifier Kv conductance. To study the propagation of voltage signals, the data were incorporated into the previously developed mathematical model. We demonstrate that the complex interaction between the passive membrane properties, Kv conductances, and the neuronal geometry leads to a resonance-like filtering of signals with peak frequencies of transmission near 15 and 40 Hz for L3 and L1/2, respectively. These results point to distinct physiological roles of different types of LMCs.