Journal: bioRxiv

Article Title: A sensorimotor brain circuit for transforming aversive experiences into emotional states

doi: 10.64898/2026.01.15.699823

Figure Lengend Snippet: CnF-LA/B pathway instructs aversive memory formation. a ) Fear conditioning paradigm with laser inhibition during the peri-shock period (top) and viral/optogenetic strategy (bottom). b ) Optogenetic inactivation of CnF-LA/B projecting cell bodies reduces auditory fear memory formation. Top, acquisition. Bottom, memory retrieval (one-way ANOVA, F (2, 16) = 14.61, P =0.0002). c ) Optogenetic inhibition of CnF terminals in LA/B viral/optogenetic approach (top) and fluorophore labeled CnF terminals in LA/B (bottom). d ) Optogenetic inactivation of CnF terminals in LA/B reduces auditory fear memory formation. Top, acquisition. Bottom, memory retrieval (one-way ANOVA, F (2, 21) = 24.34, P <0.0001). e ) Conditioning paradigm for tone-laser stimulation of Cnf-LA/B pathway (top) viral/optogenetic strategy (bottom). f ) Pairing tone with optogenetic stimulation of CnF-LA/B pathway produces fear learning during the acquisition session (two-way ANOVA, F (2, 144) = 76.64, P <0.0001). Single trials on y-axis. g ) Increased conditioned freezing is maintained in ChR2 paired group at memory retrieval (one-way ANOVA, F (2, 18) = 8.471, P =0.0026). h ) Effect of optogenetic inhibition of CnF-to-LA/B pathway on escape behaviors. i ) Interpretative working model showing CnF-to-LA pathway receiving inputs from brain regions involved in aversive sensory processing and hierarchically organized defensive responding and, in turn, sending external-sensory and internal-motor information to LA/B to instruct associative emotional memory formation and enhance escape responding. ** P <0.01, *** P <0.001. Data represent mean ± SEM

Article Snippet: For all auditory fear conditioning in behavioral studies, animals were placed into a sound-isolating chamber (Med Associates) and received auditory CSs (74 dB, 5-kHz tone pips at 1 Hz with 250 ms on and 750 ms off for 20 s) and electric shock unconditioned stimuli (US) (1 sec, 0.7mA) which co-terminated with the CS.

Techniques: Inhibition, Labeling

Journal: Advanced Science

Article Title: Time‐Dependent Therapeutic Effect of S ‐Ketamine on PTSD Mediated by VTA‐OFC Dopaminergic Neurocircuit

doi: 10.1002/advs.202500805

Figure Lengend Snippet: Early instead of late administration of S ‐Ketamine alleviates PTSD‐like behavior. A) Schematic of drug injection and behavioral tests. B) Spatiotemporal feature space of movements’ components. Each dot on the scatter plot represents a movement bout. The 40 different colors indicate the corresponding 40 movement types. C) Representative ethograms of 40 movements and manually assigning annotations. D) Heatmap of the feature space probability density of each group of behavior segments. Areas with higher probability density (purple) indicate denser behavioral segments in that region, while areas with lower probability density (white) indicate sparser behavioral segments. E) Low‐dimensional representation of the four animal groups generated through UMAP dimensionality reduction. F) Movements transferred to freezing between four groups. The size of the colored circle represents the proportion of the corresponding behavior, and the diameter of the line segment represents the number of transformations. F (3, 31) = 1.514, one‐way ANOVA with Tukey test. G) Freezing responses to the CS during fear conditioning (F (3, 155) = 0.2713), extinction (Day 1: F (3, 201) = 9.297; Day 2: F (3, 186) = 8.546), and extinction retrieval (F (3, 186) = 6.691), two‐way repeated measures ANOVA. (H) Freezing responses during fear renewal, F (3, 31) = 2.385, one‐way ANOVA with Tukey test. NO‐PTSD, PTSD+Saline, PTSD+LK, n = 9 mice, PTSD+EK, n = 8 mice. Data are presented as means ± SEM, * p <0.05, ** p <0.01, *** p <0.001. PDF, probability density function; UMAP, uniform manifold approximation and projection.

Article Snippet: All auditory fear conditioning and extinction procedures were performed using the Ugo Basile Fear Conditioning System (UGO BASILE SRL, Italy).

Techniques: Injection, Generated, Saline

Journal: Advanced Science

Article Title: Time‐Dependent Therapeutic Effect of S ‐Ketamine on PTSD Mediated by VTA‐OFC Dopaminergic Neurocircuit

doi: 10.1002/advs.202500805

Figure Lengend Snippet: Early S ‐ketamine intervention facilitates fear extinction by reversing VTA DA neuronal hypoactivity in PTSD progression. A) Representative raster plot of DA neurons. B–E) Firing rate (B, p = 0.0001, Kruskal–Wallis test), cumulative distribution and comparison of the burst index (the ratio of burst events to the total number of spikes) (C, F (3, 110) = 0.9053, p = 0.0004, one‐way ANOVA with Tukey test), bursts duration (D, p = 0.0159, Kruskal–Wallis test) and spikes in bursts (E, p <0.0001, Kruskal‐Wallis test) of DA neurons. n = 32 units in no‐PTSD group, n = 29 units in PTSD+Saline group, n = 29 units in PTSD+EK group, and n = 24 units in PTSD+LK group; n = 6 mice. F) Schematic of chemogenetic excitation behavioral tests. G) Freezing responses to the CS during fear conditioning (F (1, 75) = 0.01719, p = 0.896), extinction (Day 1: F (1, 90) = 8.314, p = 0.0049; Day 2: F (1, 90) = 4.333, p = 0.0402) and extinction retrieval (F (1, 90) = 11.90, p = 0.0009); mCherry, n = 8 mice; hM3Dq, n = 9 mice; two‐way repeated measures ANOVA. H) Freezing responses during fear renewal; mCherry, n = 8 mice; hM3Dq, n = 9, mice; t (15) = 0.1613, p = 0.874; unpaired t test. I) Schematic of chemogenetic inhibition behavioral tests. J) Freezing responses to the CS during fear conditioning (F (1, 80) = 1.012, p = 0.3174), extinction (Day 1: F (1, 96) = 9.045, p = 0.0034; Day 2: F (1, 96) = 14.56, p = 0.0002) and extinction retrieval (F (1, 96) = 9.629, p = 0.0025); mCherry, n = 8 mice; hM4Di, n = 10 mice; two‐way repeated measures ANOVA. K) Freezing responses during fear renewal; mCherry, n = 8 mice; hM4Di, n = 10 mice; t (16) = 0.4292, p = 0.6735; unpaired t test. Data are presented as means ± SEM, * p <0.05, ** p <0.01, *** p <0.001.

Article Snippet: All auditory fear conditioning and extinction procedures were performed using the Ugo Basile Fear Conditioning System (UGO BASILE SRL, Italy).

Techniques: Comparison, Saline, Inhibition

Journal: Advanced Science

Article Title: Time‐Dependent Therapeutic Effect of S ‐Ketamine on PTSD Mediated by VTA‐OFC Dopaminergic Neurocircuit

doi: 10.1002/advs.202500805

Figure Lengend Snippet: Early S ‐ketamine intervention induces hypersensitivity of VTA DA neurons, promoting fear extinction. A) Schematic of optical fiber implantation, viral injection (left), and representative image of Gcamp6s and tyrosine hydroxylase (TH) fluorescence co‐expression in the VTA and localization of fiber in the VTA (right). B) Schematic of calcium recording. C) Heatmap of calcium signals aligned to the onset of the CS during fear extinction in each trial. D) Average calcium signals in four groups (left) and the peak calcium signals during the CS for each trial across four groups (right) during extinction day 1. n = 5, F (3, 96) = 11.54, p <0.0001); two‐way repeated measures ANOVA. E) Average calcium signals in four groups (left) and the peak calcium signals during the CS for each trial across four groups (right) during extinction day 2; n = 5, F (3, 96) = 7.551, p = 0.0001); two‐way repeated measures ANOVA. F) Correlation between the average freezing time ratio and the average calcium peak for each mouse. G) Schematic of optogenic excitation during extinction. H) Freezing responses to the CS during fear conditioning (F (1, 90) = 0.5126, p = 0.4759), extinction (Day 1: F (1, 108) = 17, p <0.0001; Day 2: F (1, 108) = 14.22, p = 0.0003) and extinction retrieval (F (1, 108) = 27.48, p <0.0001); n = 10, two‐way repeated measures ANOVA. I) Freezing responses during fear renewal; n = 10, t (18) = 0.03649, p = 0.9713; unpaired t test. J) Schematic of optogenic inhibition during extinction. K) Freezing responses to the CS during fear conditioning (F (1, 80) = 0.2124, p = 0.6462), extinction (Day 1: F (1, 96) = 15.81, p = 0.0001; Day 2: F (1, 96) = 23.80, p <0.0001) and extinction retrieval (F (1, 96) = 7.393, p = 0.0078); n = 9, two‐way repeated measures ANOVA. L) Freezing responses during fear renewal, n = 9; t (16) = 0.2481, p = 0.8072; unpaired t ‐test. Data are presented as means ± SEM, ** p <0.01, *** p <0.001, **** p <0.0001.

Article Snippet: All auditory fear conditioning and extinction procedures were performed using the Ugo Basile Fear Conditioning System (UGO BASILE SRL, Italy).

Techniques: Injection, Fluorescence, Expressing, Inhibition

Journal: Advanced Science

Article Title: Time‐Dependent Therapeutic Effect of S ‐Ketamine on PTSD Mediated by VTA‐OFC Dopaminergic Neurocircuit

doi: 10.1002/advs.202500805

Figure Lengend Snippet: Activation of VTA DA ‐OFC by early administration of S ‐ketamine rescues fear extinction impairment after PTSD. A) Schematic of AAV injection to observe VTA DA neuronal projections. B) Representative image of mCherry and tyrosine hydroxylase (TH) fluorescence co‐expression in the VTA (left) and mCherry expression in the OFC region (right). C) Schematic of viral infection and optical fiber implantation to observe changes in DA neurotransmitter levels within the OFC following activation of VTA DA neurons. D) Average calcium signals and heatmap of calcium signals in each mouse (left) and the peak during activation of VTA DA neurons (right); n = 6, W = 21, p = 0.0313, paired Wilcoxon test. E) Schematic of optogenetic excitation of the VTA DA ‐OFC circuit during extinction. F) Freezing responses to the CS during fear conditioning (F (1, 80) = 1.105, p = 0.2963), extinction (Day 1: F (1, 96) = 42.65, p <0.0001; Day 2: F (1, 96) = 8.793, p = 0.0038) and extinction retrieval (F (1, 96) = 7.430, p = 0.0076); mCherry, n = 8 mice; ChR2, n = 10 mice; two‐way repeated measures ANOVA. G) Freezing responses during fear renewal; mCherry, n = 8 mice; n = 10 mice; t (16) = 0.2681, p = 0.7921, unpaired t test. H) Schematic of optogenetic inhibition of the VTA DA ‐OFC circuit during extinction. I) Freezing responses to the CS during fear conditioning (F (1, 75) = 0.1260, p = 0.7237), extinction (Day 1: F (1, 90) = 22.81, p <0.0001; Day 2: F (1, 90) = 17.88, p <0.0001) and extinction retrieval (F (1, 90) = 7.303, p = 0.0082); mCherry, n = 9 mice; NpHR, n = 8 mice; two‐way repeated measures ANOVA. J) Freezing responses during fear renewal; mCherry, n = 9 mice; NpHR, n = 8 mice; p = 0.9829, unpaired Mann‐Whitney U test. Data are presented as means ± SEM, * p <0.05, ** p <0.01, **** p <0.0001.

Article Snippet: All auditory fear conditioning and extinction procedures were performed using the Ugo Basile Fear Conditioning System (UGO BASILE SRL, Italy).

Techniques: Activation Assay, Injection, Fluorescence, Expressing, Infection, Inhibition, MANN-WHITNEY

Journal: Advanced Science

Article Title: Time‐Dependent Therapeutic Effect of S ‐Ketamine on PTSD Mediated by VTA‐OFC Dopaminergic Neurocircuit

doi: 10.1002/advs.202500805

Figure Lengend Snippet: Activation of VTA DA projection‐innervated neurons in OFC by early administration of S ‐Ketamine rescues fear extinction impairment after PTSD. A) Schematic of viral infection to anterograde tracing. B) Representative micrograph and quantification of VTA DA projection‐innervated neurons in OFC, EYFP labels VTA DA projection‐innervated neurons in OFC, n = 3. C) Schematic of viral infection and optical fiber implantation. D) Freezing responses to the CS during fear conditioning (F (1, 65) = 0.1705, p = 0.681), extinction (Day 1: F (1, 78) = 40.76, p <0.0001; Day 2: F (1, 78) = 31.44, p <0.0001) and extinction retrieval (F (1, 78) = 50.49, p <0.0001); mCherry, n = 7 mice, ChR2, n = 8 mice; two‐way repeated measures ANOVA. E) Freezing responses during fear renewal; mCherry, n = 7 mice; n = 8 mice; U = 7, p = 0.014, unpaired Mann‐Whitney U test. F) Freezing responses to the CS during fear conditioning (F (1, 70) = 1.278, p = 0.2622), extinction (Day 1: F (1, 84) = 7.220, p = 0.0087; Day 2: F (1, 84) = 14.94, p = 0.0002) and extinction retrieval (F (1, 84) = 12.26, p = 0.0007); mCherry, n = 8 mice; NpHR, n = 8 mice; two‐way repeated measures ANOVA. G) Freezing responses during fear renewal; mCherry, n = 8 mice; NpHR, n = 8 mice; p = 0.4219, t (14) = 0.8274, unpaired t test. Data are presented as means ± SEM, * p <0.05, ** p <0.01, *** p <0.001, **** p <0.0001.

Article Snippet: All auditory fear conditioning and extinction procedures were performed using the Ugo Basile Fear Conditioning System (UGO BASILE SRL, Italy).

Techniques: Activation Assay, Infection, Anterograde Tracing, MANN-WHITNEY

Journal: Advanced Science

Article Title: Time‐Dependent Therapeutic Effect of S ‐Ketamine on PTSD Mediated by VTA‐OFC Dopaminergic Neurocircuit

doi: 10.1002/advs.202500805

Figure Lengend Snippet: TI‐NIBS enhances dopaminergic release in OFC extending the therapeutic time window of S ‐ketamine for PTSD treatment. A) Schematic representation of TI‐NIBS electrode placement and its mechanism of action (left) and simulation diagram of the stimulation area (right). B) Representative images showing c‐Fos expression in OFC in No‐TI and TI groups (left) and number of cells immunoreactive for c‐Fos in OFC; No‐TI, n = 7 mice; TI, n = 6 mice; t (11) = 9.505, p <0.0001, unpaired t ‐test. C) Schematic of the mechanism of the GRAB DA3.0 sensor (left) and representative images of its expression in OFC (right). D) Average DA signals in two groups, with S ‐ketamine injection and TI‐NIBS at time point 0 s (left) and the peak calcium signals before and after drug administration between the two groups; n = 6, F (1, 20) = 7.380, p = 0.0133, two‐way ANOVA with Tukey test. E) Representative ethograms of 13 movements. F) The fraction of five behavioral categories; F (4, 140) = 96.33, p <0.0001, two‐way repeated measures ANOVA. G) Movements transferred to freezing between three groups; F (2, 28) = 0.7183, p <0.0001, one‐way ANOVA. H) Low‐dimensional representation of the four animal groups generated through UMAP dimensionality reduction. I) Freezing responses to the CS during fear conditioning (F (2, 140) = 0.5189, p = 0.5963), extinction (Day 1: F (2, 168) = 20.62, p <0.0001; Day 2: F (2, 168) = 14.79), p <0.0001, and extinction retrieval (F (2, 168) = 11.59, p <0.0001); two‐way repeated measures ANOVA. J) Freezing responses during fear renewal; F (2, 28) = 1.415, p = 0.6848, one‐way ANOVA with Tukey test. LK+No‐TI, n = 11 mice; LK+ TI, n = 10 mice; EK+No‐TI, n = 10 mice. Data are presented as means ± SEM, ** p <0.01, *** p <0.001, **** p <0.0001.

Article Snippet: All auditory fear conditioning and extinction procedures were performed using the Ugo Basile Fear Conditioning System (UGO BASILE SRL, Italy).

Techniques: Expressing, Injection, Generated

Journal: Frontiers in Cellular Neuroscience

Article Title: PTEN in somatostatin neurons regulates fear and anxiety and is required for inhibitory synaptic connectivity within central amygdala

doi: 10.3389/fncel.2025.1597131

Figure Lengend Snippet: Conditional knockout of PTEN from SOM neurons leads to elevated fear and anxiety phenotype. (a) Breeding strategy. (b) Experimental timeline for behavior (vertical dashes indicate days). (c) Both sets of mice interacted significantly more with social targets than with non-social targets (the empty cup) in the sociability stage (WT: n = 10, 115.6 s vs. 41.01 s, **** indicates Tukey’s test: p < 0.0001, KO: n = 12, 111.2 s vs. 54.65 s, **** indicates Tukey’s test: p < 0.0001). (d) SOM-PTEN-KO mice showed a higher preference for novel mice, compared to wild type mice, in the social novelty test (WT: n = 10, 78.14 s vs. 51.90 s, Tukey’s test: p = 0.2526, KO: n = 12, 110.0 s vs. 45.20 s, **** indicates Tukey’s test: p < 0.0001). (e) No significant difference was observed between wild type and knock out mice when comparing their social preference ratios. (f) SOM-PTEN-KO mice have reduced locomotion in the open field ( n = 10 WT and 13 KO, 32.53 m vs. 26.43 m, * indicates t -test: p = 0.0446). (g) SOM-PTEN-KO mice showed a trend toward less exploratory rearing in the open field ( n = 10 WT and 13 KO, 103.8 vs. 82.38, p = 0.0684). (h) Wild type and knock out mice show no difference in time exploring the center, edge, or corner zones of the open field. (i) SOM-PTEN-KO mice spent more time in the corners during the hole board test [two-way ANOVA for interaction: F (2,42) = 7.058, p = 0.0023, 286.8 s WT vs. 351.2 s KO, * indicates Sidak’s post-hoc test: p = 0.013]. (j) No differences observed in number or distribution of holes poked. (k) SOM-PTEN-KO mice spent less time in the light (174.9 s WT vs. 351.2 s KO, * indicates Sidak’s test: p = 0.0133) and more time in the dark (414.3 s WT vs. 477.0 s KO, * indicates Sidak’s test: p = 0.0053) compared to WT mice in the light/dark chamber. (l) In the Elevated-Plus Maze, knock out mice spent less time in the open arm and more time in the closed arm compared to wild type mice (open arm: 115.5 s WT vs. 93.8 s KO, closed arm: 378.6 s WT vs. 428.2 s KO, * indicates Sidak’s test: p = 0.0295). (m) Input/output curves reveal an increased startle response in SOM-PTEN-KO mice [ n = 10 WT and 13 KO mice, two-way ANOVA F (1,168) = 5.243, p = 0.0211]. (n) Normalized PPI shows no difference between wild type and knock out mice in sensory integration [ n = 10 WT and 13 KO mice, two-way ANOVA – PPI effect: F (5,120) = 4.436, p = 0.0010, genotype effect: F (1,120) = 1.289, p = 0.2585]. (o) Both genotypes readily acquire fear memory, but SOM-PTEN-KO mice show elevated levels of freezing during conditioning compared to their wild type littermates [ n = 10 WT and 13 KO mice, two-way ANOVA – conditioning effect: F (6,147) = 12.01, p = 0.0001, * indicates genotype effect: F (1,147) = 4.480, p = 0.0360]. (p) Both knock out and wild type mice can discriminate between CS+ and CS−, but SOM-PTEN-KO mice freeze more to the CS+ ( n = 10 WT and 13 KO mice, 57.17% vs. 68.91%, * indicates nested t -test: p = 0.0364).

Article Snippet: Differential auditory fear conditioning tests were conducted using a Med Associates (Fairfax, VT, USA) fear conditioning chamber (10” × 11.5” × 8.5”) inside a sound attenuating box (25” × 30” × 17”).

Techniques: Knock-Out