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Key points

  • Using functional mapping assays, we conducted a quantitative assessment of both excitatory and inhibitory synaptic laminar connections to excitatory neurons in layers 2/3–6 of the mouse visual cortex (V1).
  • Laminar‐specific synaptic wiring diagrams of excitatory neurons were constructed on the basis of circuit mapping.
  • The present study reveals that that excitatory and inhibitory synaptic connectivity is spatially balanced across excitatory neuronal networks in V1.

Abstract

In the mammalian neocortex, excitatory neurons provide excitation in both columnar and laminar dimensions, which is modulated further by inhibitory neurons. However, our understanding of intracortical excitatory and inhibitory synaptic inputs in relation to principal excitatory neurons remains incomplete, and it is unclear how local excitatory and inhibitory synaptic connections to excitatory neurons are spatially organized on a layer‐by‐layer basis. In the present study, we combined whole cell recordings with laser scanning photostimulation via glutamate uncaging to map excitatory and inhibitory synaptic inputs to single excitatory neurons throughout cortical layers 2/3–6 in the mouse primary visual cortex (V1). We find that synaptic input sources of excitatory neurons span the radial columns of laminar microcircuits, and excitatory neurons in different V1 laminae exhibit distinct patterns of layer‐specific organization of excitatory inputs. Remarkably, the spatial extent of inhibitory inputs of excitatory neurons for a given layer closely mirrors that of their excitatory input sources, indicating that excitatory and inhibitory synaptic connectivity is spatially balanced across excitatory neuronal networks. Strong interlaminar inhibitory inputs are found, particularly for excitatory neurons in layers 2/3 and 5. This differs from earlier studies reporting that inhibitory cortical connections to excitatory neurons are generally localized within the same cortical layer. On the basis of the functional mapping assays, we conducted a quantitative assessment of both excitatory and inhibitory synaptic laminar connections to excitatory cells at single cell resolution, establishing precise layer‐by‐layer synaptic wiring diagrams of excitatory neurons in the visual cortex.

Abbreviations

aCSF
artificial cerebrospinal fluid
DAPI
4′‐6‐diamidino‐2‐phenylindole
LSPS
laser scanning photostimulation
V1
primary visual cortex
  相似文献   
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Surfactant protein A (SP-A) binds to and modulates phagocytosis of Mycobacterium tuberculosis by macrophages. We investigated the relationship between polymorphisms in the collagen regions of SP-A1 and SP-A2 genes and pulmonary tuberculosis. In the present study, seven single nucleotide polymorphisms (SNPs) (4 exonic and 3 intronic) have been identified in the collagen regions of SP-A1 and SP-A2 genes in Indian population. Two intronic polymorphisms, SP-A1C1416T ((p = 0.0000, odds ratio (OR) = 20.767,95% CI: 8.315-OR<51.870) and SP-A2C1382G (p = 0.0054; OR = 3.675, 95% CI: 1.400< OR<9.644), showed significant association with pulmonary tuberculosis (number of patients = 10, number of controls = 7). A redundant SNPA1660G of SP-A2gene showed significant association with pulmonary tuberculosis (number of patients = 17, number of controls = 19, p = 0.0000, OR = 8.94,95% CI: 3.311相似文献   
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Goal of work  Detection of cognitive impairment in patients with brain metastases is important for both patient management and clinical trials. The most commonly used cognitive screen, the Mini Mental State Examination (MMSE), though convenient, is not sensitive in these patients. More sensitive tools are less convenient and, therefore, uncommonly used. Therefore, a practical and sensitive tool is needed. The Montreal Cognitive Assessment (MoCA) is a good candidate, shown to be sensitive in detecting mild cognitive impairment in the pre-dementia setting. This study is the first to explore the MoCA in cancer patients and is aimed at determining the feasibility of administering the MoCA in brain tumor patients. The secondary objective is to explore the relationship between MoCA and MMSE scores. Patients and methods  Forty patients with brain metastases being treated with whole brain radiotherapy were prospectively accrued from January to May 2007. All patients were administered both the MoCA and MMSE. Main results  The MoCA was completed in 10 min in 88% of patients. 92% of all the patients found the MoCA to be only mildly or not at all inconvenient. Eighty percent of the patients were deemed cognitively impaired by the MoCA compared with 30% by the MMSE (p < 0.0001). Of the 28 patients with a normal MMSE, 71% had cognitive impairment according to the MoCA. Overall, 50% of the patients had an abnormal MoCA, yet normal MMSE. Conclusion  The MoCA was well tolerated and provided additional information over the MMSE, justifying further validation studies of the MoCA in brain tumor patients.  相似文献   
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Anthrax toxins significantly contribute to anthrax disease pathogenesis, and mechanisms by which the toxins affect host cellular responses have been identified with purified toxins. However, the contribution of anthrax toxin proteins to dissemination, disease progression, and subsequent immunity after aerosol infection with spores has not been clearly elucidated. To better understand the role of anthrax toxins in pathogenesis in vivo and to investigate the contribution of antibody to toxin proteins in protection, we completed a series of in vivo experiments using a murine aerosol challenge model and a collection of in-frame deletion mutants lacking toxin components. Our data show that after aerosol exposure to Bacillus anthracis spores, anthrax lethal toxin was required for outgrowth of bacilli in the draining lymph nodes and subsequent progression of infection beyond the lymph nodes to establish disseminated disease. After pulmonary exposure to anthrax spores, toxin expression was required for the development of protective immunity to a subsequent lethal challenge. However, immunoglobulin (immunoglobulin G) titers to toxin proteins, prior to secondary challenge, did not correlate with the protection observed upon secondary challenge with wild-type spores. A correlation was observed between survival after secondary challenge and rapid anamnestic responses directed against toxin proteins. Taken together, these studies indicate that anthrax toxins are required for dissemination of bacteria beyond the draining lymphoid tissue, leading to full virulence in the mouse aerosol challenge model, and that primary and anamnestic immune responses to toxin proteins provide protection against subsequent lethal challenge. These results provide support for the utility of the mouse aerosol challenge model for the study of inhalational anthrax.  相似文献   
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Diabetes mellitus is reported to impair the memory function in experimental animals. Since the mammalian hippocampus and cerebral cortex play a pivotal role in a diverse set of cognitive functions, such as novelty detection and memory, we examined the vulnerability of cortex and hippocampus regions of the brain to oxidative damage in streptozotocin (STZ) diabetic mice. We next examined the attenuating effect of extracts of Withania somnifera and Aloe vera on prevention of hippocampal and cortical cell degenerations. Doses of both plant extracts given to experimental animals were based on the evaluation of their total antioxidant activity and also their potency to reduce Fe(3+). We assayed lipid peroxidation (LPO) and protein carbonyl (PC) in both regions of the brain and observed the changes in memory and motor behavioral functions in diabetic and control mice. The results showed a significant (P < 0.05) increase in LPO and PC in hippocampus and cortical regions of STZ diabetic mice. We also found a significant impairment in both motor and memory behavioral functions in diabetic mice. However, when diabetic mice were supplemented with the extracts of Withania somnifera and Aloe vera, the oxidative damage in both brain regions was reduced as marked by a significant (p < 0.05) declines in both LPO and PC. The combination of extracts of Withania somnifera and Aloe vera was more effective in reducing oxidative damage in brain regions than the supplementation of single plant extract. The combination also lowered the blood glucose level in comparison to STZ diabetic mice. Memory impairment and motor dysfunction were also improved by the plant extracts supplementation. We conclude that impairments in the hippocampus and cortex in STZ diabetic mice are associated with an increased free radical mediated oxidative damage and that the supplementation of plant extracts showed preventive effects in attenuating oxidative damage in both brain regions possibly via antioxidative mechanisms.  相似文献   
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Summary The effect of gallamine on spontaneous and stimulation-evoked overflow of tritium was studied in the submandibular gland of the rat. The gland was perfused retrogradely and labeled with3H-noradrenaline. The stimulation-evoked (1 Hz for 60 s) overflow of tritium was facilitated by increasing concentrations of gallamine (0.3–20 mM). None of the concentrations of gallamine increased the spontaneous overflow of the tritium. The facilitatory effect of gallamine was observed in 0.3 to 5 mM calcium medium; the maximum facilitation was observed at the normal concentration of calcium (2.5 mM). The facilitatory effect of gallamine was inversely related to the frequency of stimulation (10-fold facilitation at 1 Hz and 3-fold at 10 Hz).Stimulation of the salivary gland by a single pulse (1 ms duration) in the normal medium did not evoke an overflow of tritium; however, the same stimulus produced a marked increase in the overflow in the presence of gallamine.The facilitatory action of gallamine on the release of sympathetic transmitter is ascribed to the enhanced availability of calcium ions to the secretory process resulting from blockade of potassium conductance during nerve activity.  相似文献   
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