Soluble Cytokine Receptors (sIL-2Rα, sIL-2Rβ) Induce Subunit-Specific Behavioral Responses and Accumulate in the Cerebral Cortex and Basal Forebrain

Soluble cytokine receptors are normal constituents of body fluids that regulate peripheral cytokine and lymphoid activity. Levels of soluble IL-2 receptors (sIL-2R) are elevated in psychiatric disorders linked with autoimmune processes, including ones in which repetitive stereotypic behaviors and motor disturbances are present. However, there is no evidence that sIL-2Rs (or any peripheral soluble receptor) induce such behavioral changes, or that they localize in relevant brain regions. Here, we determined in male Balb/c mice the effects of single peripheral injections of sIL-2Rα or sIL-2Rβ (0–2 µg/male Balb/c mouse; s.c.) on novelty-induced ambulatory activity and stereotypic motor behaviors. We discovered that sIL-2Rα increased the incidence of in-place stereotypic motor behaviors, including head up head bobbing, rearing/sniffing, turning, and grooming behavior. A wider spectrum of behavioral changes was evident in sIL-2Rβ-treated mice, including increases in vertical and horizontal ambulatory activity and stereotypic motor movements. To our knowledge, this is the first demonstration that soluble receptors induce such behavioral disturbances. In contrast, soluble IL-1 Type-1 receptors (0–4 µg, s.c.) didn't appreciably affect these behaviors. We further demonstrated that sIL-2Rα and sIL-2Rβ induced marked increases in c-Fos in caudate-putamen, nucleus accumbens and prefrontal cortex. Anatomical specificity was supported by the presence of increased activity in lateral caudate in sIL-2Rα treated mice, while sIL-2Rβ treated mice induced greater c-Fos activity in prepyriform cortex. Moreover, injected sIL-2Rs were widely distributed in regions that showed increased c-Fos expression. Thus, sIL-2Rα and sIL-2Rβ induce marked subunit- and soluble cytokine receptor-specific behavioral disturbances, which included increases in the expression of ambulatory activity and stereotypic motor behaviors, while inducing increased neuronal activity localized to cortex and striatum. These findings suggest that sIL-2Rs act as novel immune-to- brain messengers and raise the possibility that they contribute to the disease process in psychiatric disorders in which marked increases in these receptors have been reported

Overcoming leakage in scalable quantum error correction

Leakage of quantum information out of computational states into higher energy states represents a major challenge in the pursuit of quantum error correction (QEC). In a QEC circuit, leakage builds over time and spreads through multi-qubit interactions. This leads to correlated errors that degrade the exponential suppression of logical error with scale, challenging the feasibility of QEC as a path towards fault-tolerant quantum computation. Here, we demonstrate the execution of a distance-3 surface code and distance-21 bit-flip code on a Sycamore quantum processor where leakage is removed from all qubits in each cycle. This shortens the lifetime of leakage and curtails its ability to spread and induce correlated errors. We report a ten-fold reduction in steady-state leakage population on the data qubits encoding the logical state and an average leakage population of less than $1 \times 10^{-3}$ throughout the entire device. The leakage removal process itself efficiently returns leakage population back to the computational basis, and adding it to a code circuit prevents leakage from inducing correlated error across cycles, restoring a fundamental assumption of QEC. With this demonstration that leakage can be contained, we resolve a key challenge for practical QEC at scale.Comment: Main text: 7 pages, 5 figure

Administration of IL-2 in adults increases rearing behavior (in contrast to periadolesence).

<p>Mean (± S.E.M.) activity scores (A. Number of rearing episodes within 3 sec; B. Number of rearing against wall episodes within 3 sec; C. Total number of rearing episodes; D. Total time spent rearing (sec)) following a single injection of saline or IL-2 (0.4 µg/mouse, s.c.) and those tested 30 days later with single injection of IL-2 (0.4 µg/mouse, s.c.) administered 30 days later, as described in the figure with “+30 days” designation. Mice were exposed to the test cage immediately following cytokine administration. *p<0.05.</p

Administration of a single injection of IL-2 in periadolescent mice does not alter other motor responses (i.e. ambulatory distance or vertical activity), in contrast to the modulatory effects upon rearing shown in Figure 2.

<p>A second injection of IL-2 30-days later also did not alter these responses. Mean (± S.E.M.) activity scores ((A). Ambulatory distance (cm); (B). Number of vertical activity sessions) following a single injection of saline or IL-2 (0.4 µg/mouse, s.c.) and those tested 30 days later with single injection of IL-2 (0.4 µg/mouse, s.c.), as described in figure with “+30 days” designation. p>0.05 NS [NS = non-significance].</p

Single injection of IL-2 in periadolescent mice decreases stereotypic behaviors.

<p>Mean (± S.E.M.) activity scores (A. Jumps; B. VP STPY Time; C. CCW Turns) following a single injection of saline or IL-2 (0.4 µg/mouse, s.c.). Mice were exposed to the test cage immediately following cytokine administration. *p<0.05.</p

IL-2 administration in periadolescent mice increases sensitivity to GBR-induced stereotypic sniffing administered 30-days later in adulthood.

<p>Mean (± S.E.M.) activity score of GBR 12909-stimulated sniffing time. Mice received a single injection of saline or IL-2 (0.4 µg/mouse, s.c.), and were tested 30 days later with GBR 12909 (7 mg/kg, i.p.). Mice were exposed to the test cage immediately following GBR administration. Note that the effect was initially observed at 80-minutes post-injection (shown with arrow). *p<0.05.</p

"Ολυμπία, ακούγοντας τη μουσική των άστρων", μια πολυδιάστατη δράση για μαθητές γυμνασίου και λυκείου σε έναν τόπο συνένωσης παιδείας και πολιτισμού

Σημείωση: διατίθεται συμπληρωματικό υλικό σε ξεχωριστό αρχείο

c-Fos expression and Fluorescent staining of Nucleus Accumbens in sIL-2Rs treated mice.

<p>Photomicrographs of brain sections showing Fos-like immunoreactive cells in the nucleus accumbens of mice receiving single injection of (A) saline, (B) 1 µg sIL-2Rα or (C) 2 µg sIL-2Rβ. Abbreviations: aca, anterior commissure; Sh, shell of nucleus accumbens; Co, core of nucleus accumbens. (D) Histogram show the number (mean ± S.E.M.) indicate Fos-positive cells counted within the indicated compartments of the nucleus accumbens after administration of saline or single injections of sIL-2Rα or sIL-2Rβ. Photomicrographs of deposits of sIL-2Rα or sIL-2Rβ in shell or core of nucleus accumbens after administration of (E and F) saline or single injections of (G and H) sIL-2Rα or (I and J) sIL-2Rβ. Photomicrographs showing merged c-Fos and Fluorescent staining in sIL-2Rα treated mice (K) and sIL-2Rβ treated mice (L). [Arrow head: - Fluorescent staining; Arrow: - c-fos staining].</p