Psilocybin triggers an activity-dependent rewiring of large-scale cortical networks.

Comparative basolateral amygdala connectomics reveals dissociable single-neuron projection patterns to frontal cortex in macaques and mice

Objective To determine the expression of murine double minute 2 (Mdm2) in the frontal cortex of mice after intervention with Amphetamine. Methods Male C57BL/6 mice were randomly divided into the normal control group (n=10) , normal saline group (n=10) and Amphetamine group (n=40) . The Amphetamine group was divided into 1, 7, 14 and 28 d subgroups, and was intraperitoneally injected with 2 mg·kg-1·d-1 Amphetamine, 1 time/d. The normal saline group was injected with equal volume of normal saline, and the normal control group received no treatment. The autonomous behavior activities were tested during establishing the models. Immunohistochemistry and Western blotting were used to examine the Mdm2 expression in frontal cortex of the mice. Results The total moving distance, average speed, maximum speed, fast moving time/total time ratio in the 7, 14 and 28 d Amphetamine subgroups were significantly increased compared with those in the normal control group and normal saline group, and there were statistically significant differences (P<0.05) . Immumohistochemistry showed that the grey values of Mdm2-positive inummoreactive products in the Amphetamine group were significantly lower than those in the normal control group and normal saline group, and there were statistically significant differences (P<0.05) . The grey values of the positive inummoreactive products in the Amphetamine 14 d subgroup was significantly decreased compared with those in the Amphetamine 1 d subgroup, and there were statistically significant differences[1 d (213.31±6.78) , 14 d (192.82±7.90) , P<0.05]. The findings of Western blotting showed that Mdm2 protein expression in the frontal cortex was elevated in the Amphetamine group compared with that in the other two groups. Conclusion Amphetamine can significantly increase Mdm2 expression in the frontal cortex of mice. Key words: Amphetamines; Prefrontal cortex; Mice; Double minute 2

Our recent study demonstrated that local perfusion of ethanol (EtOH) and acetaldehyde (AcH) into the hippocampus via microdialysis decreased extracellular glutamate; however, it is not clear whether this effect occurs in the frontal cortex. To address this issue, we investigated the effects of local perfusion of EtOH and AcH on extracellular glutamate in the frontal cortex of Aldh2-knockout (Aldh2-KO) and C57BL/6 N [wild-type (WT)] mice. Dialysates were collected every 20 minutes, and extracellular glutamate was measured using HPLC coupled with electrochemical detector. We found local perfusion of 200 and 500 mM EtOH into the frontal cortex of WT and Aldh2-KO mice produced significant decreases in extracellular glutamate levels (P < 0.05). A dose of 500 mM EtOH induced a greater decrease in Aldh2-KO mice (P < 0.05) than in WT mice, indicating the action of AcH. Similarly, perfusion of 200 and 500 µM AcH decreased glutamate in the frontal cortex of Aldh2-KO mice (P < 0.05), but this decrease was not seen in WT mice at any AcH dose, due to the subsequent oxidation of AcH by mitochondrial aldehyde dehydrogenase 2. A low dose of EtOH (100 mM) or AcH (100 µM) had no effect on glutamate. These results showed that high doses of EtOH and AcH induces a significant decrease in extracellular glutamate in the frontal cortex of mice, replicating previous findings and providing further evidence that reduced glutamate is likely to be involved in the depressant effects of EtOH.

Providing lysophosphatidylcholine-bound omega-3 fatty acids increased eicosapentaenoic acid, but not docosahexaenoic acid, in the cortex of mice with the apolipoprotein E3 or E4 allele.

It is generally believed that fear extinction is a form of new learning that inhibits rather than erases previously acquired fear memories. Although this view has gained much support from behavioural and electrophysiological studies, the hypothesis that extinction causes the partial erasure of fear memories remains viable. Using transcranial two-photon microscopy, we investigated how neural circuits are modified by fear learning and extinction by examining the formation and elimination of postsynaptic dendritic spines of layer-V pyramidal neurons in the mouse frontal association cortex. Here we show that fear conditioning by pairing an auditory cue with a footshock increases the rate of spine elimination. By contrast, fear extinction by repeated presentation of the same auditory cue without a footshock increases the rate of spine formation. The degrees of spine remodelling induced by fear conditioning and extinction strongly correlate with the expression and extinction of conditioned fear responses, respectively. Notably, spine elimination and formation induced by fear conditioning and extinction occur on the same dendritic branches in a cue- and location-specific manner: cue-specific extinction causes formation of dendritic spines within a distance of two micrometres from spines that were eliminated after fear conditioning. Furthermore, reconditioning preferentially induces elimination of dendritic spines that were formed after extinction. Thus, within vastly complex neuronal networks, fear conditioning, extinction and reconditioning lead to opposing changes at the level of individual synapses. These findings also suggest that fear memory traces are partially erased after extinction.

Aldehyde dehydrogenase 2 deficiency increases resting-state glutamate and expression of the GluN1 subunit of N-methyl-d-aspartate receptor in the frontal cortex of mice

Context. Ziziphi Spinosae Semen (ZSS) is a well-known Chinese herbal medicine used in the treatment of depression and anxiety in China. ZSS contains several active components, such as alkaloids, saponins, and flavonoids. Objective. This study aimed to explore the synergistic effect of alkaloids and saponins from ZSS in alleviating depression in a mouse model. Materials and Methods. Modeling depression with chronic unpredictable stimuli. Pharmacodynamic methods (tail suspension test and forced swimming test) were used to evaluate the antidepressant effects of alkaloids, saponins, and combinations thereof from ZSS. The mechanisms underlying the effect were examined by measuring the levels of monoamine neurotransmitters in the hippocampus and frontal cortex of mice. Results. Compared with the model group, alkaloids therapy (AZSS), saponins therapy (SZSS), and combination therapy significantly reduced the immobility time in behavioral tests (P < 0.05). The contents of noradrenaline (NE), dopamine (DA), and serotonin (5-HT) in the hippocampus and frontal cortex of depressed mice were increased in the drug treatment groups, especially in the combination group, which increased by 14.65%, 87.72%, 33.44%, 25.64%, 25.39%, and 70.78%, respectively. Several groups showed better results (P < 0.05), especially the combination of alkaloids and saponins. Discussion and Conclusion. The saponins and alkaloids from ZSS exhibited a synergistic effect in improving the behavior of depressed mice. More importantly, the combination of alkaloids (15 mg·kg−1) and saponins (110 mg·kg−1) was effective in alleviating depression in mice, especially in terms of changing the level of DA in the hippocampus.

Neuron-specific phosphorylation of c-Jun N-terminal kinase increased in the brain of hypoxic preconditioned mice

Isoorientin (ISO) is considered one of the most important flavonoids with various pharmacological effects such as antioxidant, anti-inflammatory, and anti-cancer activities. Despite these beneficial activities, the effects of ISO on learning and memory have not been investigated so far. The current study evaluated the memory-enhancing effects of ISO in a scopolamine-treated mouse model by using the Y-maze and passive avoidance tests. The results showed that ISO (5 and 10mg/kg, p.o.) treatment significantly improved the cognitive impairments caused by scopolamine. Additionally, ISO significantly decreased scopolamine-induced acetylcholinesterase and thiobarbituric acid reactive substance activities in both the hippocampus and frontal cortex of mice. In addition, ISO significantly increased the levels of total superoxide dismutase induced by scopolamine in the hippocampus and frontal cortex. Moreover, Western blot results indicated that ISO reversed the decreases in expression of phosphorylated cAMP response element binding (CREB) and brain-derived neurotrophic factor (BDNF) in the hippocampus and frontal cortex of scopolamine-treated mice. Thus, our results provide initial evidence that ISO ameliorates scopolamine-induced memory and cognitive impairments partly by restoring the cholinergic system, antioxidant defense, and p-CREB/BDNF signaling pathway, thereby exhibiting memory-enhancing activities.

Long term effects of murine postnatal exposure to decabromodiphenyl ether (BDE-209) on learning and memory are dependent upon APOE polymorphism and age

Effects of antidepressant drugs and GR 205171, an neurokinin-1 (NK 1) receptor antagonist, on the response in the forced swim test and on monoamine extracellular levels in the frontal cortex of the mouse

The effects of n-acetylcysteine and/or deferoxamine on manic-like behavior and brain oxidative damage in mice submitted to the paradoxal sleep deprivation model of mania

The effects of chronic fluoxetine treatment following injury of medial frontal cortex in mice

Impacts of FKBP5 variants on large-scale brain network connectivity in healthy adults

The basolateral amygdala (BLA) projects to the frontal cortex (FC) in both rodents and primates, but the comparative organization of single-neuron BLA-FC projections is unknown. Using a barcoded connectomic approach, we found that BLA neurons are more likely to project to multiple distinct parts of FC in mice than in macaques. Further, while single BLA neuron projections to nucleus accumbens are similarly organized in mice and macaques, BLA-FC connections differ.