Journal: Science Advances

Article Title: Impaired parvalbumin interneurons in the retrosplenial cortex as the cause of sex-dependent vulnerability in Alzheimer’s disease

doi: 10.1126/sciadv.adt8976

Figure Lengend Snippet: ( A ) Timeline of surgery and behavioral testing. ( B ) pAAV-s5e2-Gq-P2A-d Tomato expression (green) and 4′,6-diamidino-2-phenylindole (DAPI) (grayscale). Scale bars, 1 mm. ( C ) Percentage of time spent in the novel arm of the forced alternation Y-maze task by male mice with saline treatment and subsequent DCZ treatment. ( D ) Percentage of time spent in the novel arm of the forced alternation Y-maze task by female mice with saline treatment and subsequent DCZ treatment. *P = 0.0349, a priori two-sample t test. ( E ) Activity suppression ratio following contextual conditioning by male mice treated with saline or DCZ. ( F ) Activity suppression ratio following contextual conditioning by female mice treated with saline or DCZ. *P = 0.0088, a priori two-sample t test. ( G ) Photomicrographs showing s5e2 (green) and c-Fos (grayscale) staining in the RSC with saline and DCZ treatments. Scale bars, 50 μm. ( H ) Percentage of s5e2 + cells that were co-localized with c-Fos with saline and DCZ treatment. *P < 0.0001, two-sample t test. ( I ) c-Fos expression density in s5e2-negative cells across the RSC in male WT and 5xFAD mice treated with saline of DCZ. *P = 0.0075, two-way ANOVA (genotype × treatment). ( J ) c-Fos expression density in s5e2-negative cells across the RSC in female WT and 5xFAD mice treated with saline of DCZ. *P = 0.0207, two-way ANOVA (genotype × treatment). Data represent means ± SEM. Group sizes have been presented in parentheses alongside of each plot. See also fig. S6. All statistical comparisons have been provided in table S3.

Article Snippet: Contextual conditioning took place in Ugo Basile (Gemonio, Italy) contextual fear conditioning chambers (17 cm by 17 cm) placed inside of sound attenuating cabinets.

Techniques: Expressing, Saline, Activity Assay, Staining

Journal: PLoS ONE

Article Title: SAHA Enhances Synaptic Function and Plasticity In Vitro but Has Limited Brain Availability In Vivo and Does Not Impact Cognition

doi: 10.1371/journal.pone.0069964

Figure Lengend Snippet: A) Compared to non-transgenic littermates (n = 15), Tg2576 (n = 14) mice showed significantly less freezing than wt mice when returned to the context in which conditioning occurred (context, p<0.001), when placed in an altered context (altered, p<0.01), or in response to the cue used for conditioning (cue, p<0.05). B) Tg2576 mice were treated daily for 33 days prior to, as well as during fear conditioning with either vehicle (n = 14), 25 mg/kg SAHA (n = 13), or 50 mg/kg SAHA (n = 13). There was no effect of treatment on the percentage of time Tg2576 mice spent freezing in response to the context, altered context, or cue (p>0.05). C) There was no effect of treatment on the percentage of time spent freezing during conditioning (p>0.05). D) There was no effect of treatment on the distance traveled in the open field test (total distance = 38.0±7.7 m for vehicle, 39.6±6.1 m for 25 mg/kg SAHA, and 34.2±5.2 m for 50 mg/kg SAHA, p>0.05). All data are plotted as mean ±SEM.

Article Snippet: Contextual fear conditioning was performed at Cerebricon, Ltd., (Finland).

Techniques: Transgenic Assay

Journal: Nature Communications

Article Title: Experience-dependent resonance in amygdalo-cortical circuits supports fear memory retrieval following extinction

doi: 10.1038/s41467-020-18199-w

Figure Lengend Snippet: a Firing rate of BLA MUA is not significantly different during 4 Hz and 8 Hz sinusoidal stimulation in the conditioned context (firing rate normalized to no light; paired two-tailed Wilcoxon test: P = 0.22, n = 50 MUA). b Same as in a but in unconditioned context (paired two-tailed Wilcoxon test: P = 0.33, n = 50 MUA). c Averaged PPC spectra (left) of BLA MUA during 4 Hz and 8 Hz optical stimulation in the conditioned context (Fear + Ext memory state). MUA phase-locking quantified as 4:8 Hz PPC ratio (right) is significantly shifted by 4 Hz vs. 8 Hz stimulation in the memory-context (paired two-tailed Wilcoxon test: P = 0.0005, n = 50 MUA). d Same as in c but in the unconditioned context (no memory state). MUA phase-locking is not significantly shifted by 4 Hz vs. 8 Hz stimulation in the unconditioned context (paired two-tailed Wilcoxon test: P = 0.17, n = 50 MUA). e Venn diagram showing the distribution of units significantly phase-locked to 4 Hz stimulus waveform in the conditioned (Fear + Ext) context (left), unconditioned neutral context (right), or both (middle overlap). f Proportion of units recruited to freezing-associated 4 Hz oscillations in the conditioned context is enriched among units that significantly phase-lock to 4 Hz stimulation in the conditioned context (Chi-square test: X 2 = 8.24, P = 0.0041, n = 17 units). g Same as e but for 8 Hz stimulation. h Proportion of units recruited to non-freezing-associated 8 Hz oscillations in the conditioned context among units that significantly phase-lock to 8 Hz stimulation in the conditioned versus unconditioned context (Chi-square test: X 2 = 1.94, P = 0.16, n = 14 units: one of the six Fear+Ext-only units in panel g did not meet the minimum number of spike criterium for PPC analysis during the non-freezing behavioral state). All error bars and shaded area: mean ± SEM.

Article Snippet: MUA phase-locking is not significantly shifted by 4 Hz vs. 8 Hz stimulation in the unconditioned context (paired two-tailed Wilcoxon test: P = 0.17, n = 50 MUA). e Venn diagram showing the distribution of units significantly phase-locked to 4 Hz stimulus waveform in the conditioned (Fear + Ext) context (left), unconditioned neutral context (right), or both (middle overlap). f Proportion of units recruited to freezing-associated 4 Hz oscillations in the conditioned context is enriched among units that significantly phase-lock to 4 Hz stimulation in the conditioned context (Chi-square test: X = 8.24, P = 0.0041, n = 17 units). g Same as e but for 8 Hz stimulation. h Proportion of units recruited to non-freezing-associated 8 Hz oscillations in the conditioned context among units that significantly phase-lock to 8 Hz stimulation in the conditioned versus unconditioned context (Chi-square test: X = 1.94, P = 0.16, n = 14 units: one of the six Fear+Ext-only units in panel g did not meet the minimum number of spike criterium for PPC analysis during the non-freezing behavioral state).

Techniques: Two Tailed Test

Journal: Nature Communications

Article Title: Experience-dependent resonance in amygdalo-cortical circuits supports fear memory retrieval following extinction

doi: 10.1038/s41467-020-18199-w

Figure Lengend Snippet: a Schematic of optogenetic strategy to increase frequency-specific functional interactions between the BLA and mPFC. b Example images showing ChR2-mCherry expression, with optical fiber and electrode placement in mPFC and BLA. Targeting was similarly confirmed by histological analysis in all 11 mice; see Methods section for detail. Scale bar: 300 µm. c , d Representative cross-power spectrograms illustrating differential effects of 4 Hz in- and anti-phase optical stimulation in the conditioned context ( c ; fear+ext memory state) and unconditioned novel context ( d ; no-memory state). e Averaged cross-power spectra comparing effects of in-phase and anti-phase 4 Hz stimulation to no-stimulation baseline during fear+extinction memory and no-memory states ( n = 8 mice). f Quantification of the cross-power spectra from e . 4 Hz in-phase stimulation increases the 4:8 Hz cross-power ratio compared to the no-stimulation baseline, whereas 4 Hz anti-phase stimulation does not. This effect is absent in a context where the mouse has no fear memory (two-way RM ANOVA: trial F (1,7) = 34.12, P = 0.0006, stimulation F (2,14) = 7.80, P = 0.0053, trial × stimulation F (2,14) = 7.46, P = 0.0062, n = 8 mice. Holm-Sidak’s multiple comparisons test; fear+ext memory state: no light vs. 4 Hz anti-phase: t (14) = 2.01, P = 0.064; no light vs. 4 Hz in-phase t (14) = 3.39, P = 0.0087. No memory state: no light vs. 4 Hz anti-phase: t (14) = 0.33, P = 0.94; no light vs. 4 Hz in-phase t (14) = 0.29, P = 0.94). g 4 Hz in-phase stimulation increases the conditioned freezing response compared to the no-stimulation baseline, whereas 4 Hz anti-phase stimulation does not. This effect is absent in a context where the mouse has no fear memory (two-way repeated measures ANOVA: trial F (1,10) = 15.43, P = 0.0028, stimulation F (2,20) = 10.18, P = 0.0009, trial × stimulation F (2,20) = 5.28, P = 0.014, n = 11 mice. Holm-Sidak’s multiple comparisons test; fear+ext memory state: no light vs. 4 Hz anti-phase: t (20) = 0.55, P = 0.59; no light vs. 4 Hz in-phase t (20) = 5.20, P < 0.0001. No memory state: no light vs. 4 Hz anti-phase: t (20) = 0.0088, P = 0.99; no light vs. 4 Hz in-phase t (20) = 0.97, P = 0.71). All error bars and shaded area: mean ± SEM.

Article Snippet: MUA phase-locking is not significantly shifted by 4 Hz vs. 8 Hz stimulation in the unconditioned context (paired two-tailed Wilcoxon test: P = 0.17, n = 50 MUA). e Venn diagram showing the distribution of units significantly phase-locked to 4 Hz stimulus waveform in the conditioned (Fear + Ext) context (left), unconditioned neutral context (right), or both (middle overlap). f Proportion of units recruited to freezing-associated 4 Hz oscillations in the conditioned context is enriched among units that significantly phase-lock to 4 Hz stimulation in the conditioned context (Chi-square test: X = 8.24, P = 0.0041, n = 17 units). g Same as e but for 8 Hz stimulation. h Proportion of units recruited to non-freezing-associated 8 Hz oscillations in the conditioned context among units that significantly phase-lock to 8 Hz stimulation in the conditioned versus unconditioned context (Chi-square test: X = 1.94, P = 0.16, n = 14 units: one of the six Fear+Ext-only units in panel g did not meet the minimum number of spike criterium for PPC analysis during the non-freezing behavioral state).

Techniques: Functional Assay, Expressing

Journal: Acta Neuropathologica Communications

Article Title: LAMP-2 deficiency leads to hippocampal dysfunction but normal clearance of neuronal substrates of chaperone-mediated autophagy in a mouse model for Danon disease

doi: 10.1186/s40478-014-0182-y

Figure Lengend Snippet: Abnormal behavior as a result of LAMP-2 deficiency in mice. (a) LAMP-2-deficient (LAMP-2 -/y ) mice show a significantly reduced paw area at the peak of stance in comparison with wild-type mice. (b) LAMP-2 -/y mice swim significantly slower than wild-type controls. (c) Path length during exploration of a novel environment is significantly reduced in LAMP-2 -/y mice. (d) Freezing percentage is significantly increased in LAMP-2 -/y mice during the habituation phase. There was no difference in fear conditioning and contextual or cued fear memory. (e) Y-maze working memory: LAMP-2 -/y mice make significantly less spontaneous alternations (*p < 0.05; **p < 0.01).

Article Snippet: Contextual and cued fear conditioning was evaluated in a plexiglass test chamber (26 × 22 × 18 cm high), containing a grid floor to deliver an electric shock using a constant current shocker (MED Associates Inc., St. Albans, Vermont, USA).

Techniques: Comparison