OBJECTIVE It's known that post-retrieval extinction but not extinction alone could erase fear memory.However,whether the coding pattern of original fear engrams is remod-eled or inhibited remains largely unclear.Here we try to investigate whether the coding pattern of memory engrams is altered during post-retrieval extinction induced memory updating.METHODS To answer the question,by using activity-depen-dent neuronal-tagging technology,neuronal trac-ing technique combined with optogenetic manipu-lation and in vivo calcium imaging,we identified the fear and extinction cells in PrL and BLA and investigated the dynamic encoding of memory engram ensembles in the PrL and BLA during CS versus US initiated memory updating.RESULTS We found increased reactivation of engram cells in the prelimbic cortex and basolat-eral amygdala during memory updating.More-over,conditioned stimulus and unconditioned stimulu sinitiated memory updating depend on the engram cells reactivation in the prelimbic cor-tex or basolateral amygdala respectively.Finally,we found memory updating causes increased overlapping between fear and extinction cells and the original fear engrams encoding was altered during memory updating.CONCLUSION Our data provide the first evidence to show the overlapping ensembles between fear and extinc-tion cells and functional reorganization of original engrams underlying conditioned stimulus and unconditioned stimulus initiated memory updating.

Although the function of tRNAs in the translational process is well established, it remains controversial whether tRNA abundance is tightly associated with translational efficiency (TE) in mammals. Moreover, how critically the expression of tRNAs contributes to the establishment of tissue-specific proteomes in mammals has not been well addressed. Here, we measured both tRNA expression using demethylase-tRNA sequencing (DM-tRNA-seq) and TE of mRNAs using ribosome-tagging sequencing (RiboTag-seq) in the brain, heart, and testis of mice. Remarkable variation in the expression of tRNA isodecoders was observed among different tissues. When the statistical effect of isodecoder-grouping on reducing variations is considered through permutating the anticodons, we observed an expected reduction in the variation of anticodon expression across all samples, an unexpected smaller variation of anticodon usage bias, and an unexpected larger variation of tRNA isotype expression at amino acid level. Regardless of whether or not they share the same anticodons, the isodecoders encoding the same amino acids are co-expressed across different tissues. Based on the expression of tRNAs and the TE of mRNAs, we find that the tRNA adaptation index (tAI) and TE are significantly correlated in the same tissues but not between tissues; and tRNA expression and the amino acid composition of translating peptides are positively correlated in the same tissues but not between tissues. We therefore hypothesize that the tissue-specific expression of tRNAs might be due to post-transcriptional mechanisms. This study provides a resource for tRNA and translation studies, as well as novel insights into the dynamics of tRNAs and their roles in translational regulation.
Animals ; Mice ; Anticodon/genetics* ; Transcriptome ; Protein Biosynthesis ; RNA, Transfer/chemistry* ; Amino Acids/metabolism* ; Mammals/metabolism*

Purpose To explore the application value of diffusion kurtosis imaging (DKI) in assessing brain injury in different clinical stages caused by carbon monoxide (CO) poisoning. Materials and Methods MR plain scan, diffusion weighted imaging (DWI) and DKI scans were performed in 26 patients with acute CO poisoning, 17 patients with delayed neuropsychologic sequelae (DNS), 15 patients with chronic phase, and 21 healthy volunteers (control group). The DKI parameter values in regions of interest among the four groups were compared, and the correlation between the values of each parameter and DWI apparent diffusion coefficient (ADC) value was analyzed. Results ①The mean kurtosis (MK) values in the area of pallidum in acute phase, DNS phase, and chronic phase were 1.51±0.15, 1.07±0.11 and 0.59±0.11, respectively; among which the MK value in acute phase was significantly higher than that in the control group (1.06±0.06, P<0.05), and the chronic phase was significantly lower than the DNS phase and the control group (P<0.05); compared with the control group, the MK in centrum semiovale and subcallosal zone was relatively higher in acute phase and DNS phase, lower in chronic phase, both showing the most significant increase in DNS phase (P<0.05). ②In each region of interest, the MK value and mean diffusivity (MD) all showed an increase after decrease. Among them, MD values in the area of pallidum in acute phase were significantly lower than those in DNS and control group (0.74±0.11 vs. 0.85±0.07 and 0.98±0.12, P<0.05), and the centrum semiovale and callosum were the smallest in DNS phase (0.67±0.09 and 0.80±0.05, respectively), significantly lower than that in the control group (P<0.05). ③The fractional anisotropy (FA) values of all regions of interest showed a progressive decrease in different clinical stages, in which pallidum and centrum semiovale were the lowest in chronic phase (0.19±0.04 and 0.22±0.03, respectively), significantly lower than those in DNS phase and the control group (P<0.05). ④There was a positive correlation between MD values and ADC values in different clinical stages of CO poisoning in each region of interest (P<0.01). Conclusion DKI can quantitatively evaluate the changes of brain gray matter microarchitecture after CO poisoning, which is helpful to understand the characteristics of brain injury in different clinical stages caused by CO poisoning from the microscopic level.

Purpose With the progression of brain tissue aging, the transport and drainage characteristics of metabolites and secretory products for neurons in extracellular space occurs irreversible change. This paper aims to investigate and quantify MR tracer diffusion characteristics in cerebral interstitial fluid of elderly SD rats. Materials and Methods MR contrast agent Gd-DTPA was injected into the caudate nucleus of two groups of rats including 8 in experimental group (15-17 month old) and 15 in control group (7-10 month old). MR scan was performed at 0.25 h, 0.5 h, 1 h, 2 h, 3 h and 4 h to observe the dynamic distribution in the caudate and measure the diffusion and clearance rate. Results There was no statistically significant difference in diffusion rate and D* between control group with (3.32±0.70)×10-4 mm2/s and experimental group with (3.25±0.46)×10-4 mm2/s (t=1.739, P>0.05). The clearance rate k' was significantly different between control group (0.62±0.12)×10-4/s and experimental group (0.29±0.08)×10-4/s (t=11.602, P<0.05). Conclusion The degeneration of aging brain tissue changes the composition of extracellular space resulting in decreased speed of ISF clearance. This may cause accumulation of metabolites which eventually triggers a variety of age-related diseases.