Journal: Frontiers in Pharmacology

Article Title: Elevated somatostatin interneuron long-term potentiation minimally regulates temporoammonic plasticity in a mouse model of Fragile X Syndrome

doi: 10.3389/fphar.2025.1640921

Figure Lengend Snippet: Elevated LTP in CA1 SST-INs in Fmr1 -/y mice is susceptible to GABA B R activation. (A) Overview of experiments and identity of recorded cells. Left, schema of recording configuration for measuring aTBS induced LTP in SST-INs. Middle, low magnification flattened confocal stack showing a recorded SST-IN (scale: 100 μm). Right, high magnification image of the same recorded cell (magenta and arrow) confirming SST immunoreactivity (green; scale: 20 μm). (B) Example voltage responses of SST-INs from WT (black, upper) and Fmr1 -/y (red, lower) mice, following ± 125 pA (500 ms duration) stimulation. The average action potential output of all recorded SST-INs is quantified for all current steps delivered. (C) Upper, example traces from WT (black) and Fmr1 -/y (red) mice before and after (grey and pink, respectively) induction of aTBS LTP under vehicle conditions or following 20 min pre-application of 20 μM R-baclofen. Lower, time-course plots of EPSC amplitude all WT (n = 11 cells from 8 mice) and Fmr1 -/y (n = 9 cells from 7 mice) SST-INs in vehicle and following baclofen pre-treatment (WT: n = 6 cells from 4 mice, grey; Fmr1 -/y : n = 8 cells from 6 mice, pink). (D) Comparison of the magnitude of EPSC potentiation measured under control conditions and following baclofen pre-treatment in WT and Fmr1 -/y SST-INs. (E) CV 2 analysis of aTBS LTP recordings from WT (grey circles) and Fmr1 -/y (pink circles) SST-INs. The average responses of both genotypes are depicted ±SEM (black and red, respectively) as well as the linear regression of each group (dashed lines). (F) Paired-pulse recordings from SST-INs showing stimulation location. Example paired-pulse responses in WT (upper, black) and Fmr1 -/y (lower, red), in vehicle or 20 μM baclofen. Measured PPR from SST-INs following alveus stimulation. (G) Schematic of TA LTP recording, while measuring alveus EPSCs in SST-INs showing stimulation locations. Example alveus EPSCs from WT (upper, black) and Fmr1 -/y (lower, red), before and after (grey and pink) 2 × 100 Hz stimulation to the SLM. Timecourse of alveus EPSC amplitude following TA LTP induction. Quantification of peak EPSC change 20–25 min post HFS. Data is shown as mean ± SEM (B,C,E) or box-plots depicting 25%–75% range, maximum range (D,F,G) and individual data points (open circles). Statistics shown from 2-way ANOVA (B,D,F) Mann-Whitney (G) or Wilcoxon signed-rank (D,G) tests, ns-p > 0.05, **** - p < 0.0001 from Holm-Sidak tests; or ns p > 0.05, # - p < 0.05 (Wilcoxon signed-rank test).

Article Snippet: GABA B R agonist baclofen (Bacl; 20 μM), mGluR1α antagonist LY367385 (LY; 20 μM), mGluR5 antagonist Fenobam (Feno; 10 μM), and GABA A R antagonist gabazine (10 μM) were dissolved in dH 2 O or DMSO and sourced from HelloBio (HelloBio Ltd., United Kingdom) or Tocris (Bio-Techne Ltd., United Kingdom).

Techniques: Activation Assay, Comparison, Control, MANN-WHITNEY

Journal: Frontiers in Pharmacology

Article Title: Elevated somatostatin interneuron long-term potentiation minimally regulates temporoammonic plasticity in a mouse model of Fragile X Syndrome

doi: 10.3389/fphar.2025.1640921

Figure Lengend Snippet: Comparison of GABA and mGluR modifying drugs on TA basal synaptic transmission (A) Example fEPSP traces recorded before and after drug incubation in WT (black) and Fmr1 -/y (red) mice. Drugs applied from left to right include: 20 μM baclofen (GABA B R agonist), 10 μM gabazine (GABA A R antagonist), 20 μM LY367385 (mGluR1α antagonist), 10 μM Fenobam (mGluR5 antagonist), and 10 μM s-DHPG (mGluR1/5 agonist). (B) Timecourse plots shown separately for each treatment condition and genotype. The duration of each drug application is shown above (black bar). (C) Mean fEPSP slope measured over the final 10 min of drug application for each of the drugs listed. (D) Paired-pulse ratio (PPR) before and after drug application. Data shown as mean ± SEM (B) or box-plots depicting 25%–75% range, maximum range (C,D) . WT and Fmr1 -/y sample sizes indicated in each bar); all with individual data points overlaid (open circles). Statistics shown from Mann Whitney tests (C) 2-way ANOVA (D) and Wilcoxon signed-rank tests (C) . Statistics shown as: ns-p > 0.05, * - p < 0.05; or ns p > 0.05, # - p < 0.05 (Wilcoxon signed-rank test).

Article Snippet: GABA B R agonist baclofen (Bacl; 20 μM), mGluR1α antagonist LY367385 (LY; 20 μM), mGluR5 antagonist Fenobam (Feno; 10 μM), and GABA A R antagonist gabazine (10 μM) were dissolved in dH 2 O or DMSO and sourced from HelloBio (HelloBio Ltd., United Kingdom) or Tocris (Bio-Techne Ltd., United Kingdom).

Techniques: Comparison, Transmission Assay, Incubation, MANN-WHITNEY

Journal: Frontiers in Pharmacology

Article Title: Elevated somatostatin interneuron long-term potentiation minimally regulates temporoammonic plasticity in a mouse model of Fragile X Syndrome

doi: 10.3389/fphar.2025.1640921

Figure Lengend Snippet: No genotype-specific effects of GABA modulating drugs on TA LTP in Fmr1 -/y mice. (A) Time-course of fEPSP slope following HFS (lightning bolt) at TA inputs in wild-type (WT, black) and Fmr1 -/y (red) mice, following 30 min incubation with 20 μM baclofen followed by a 20 min washout. Inset, example fEPSP traces from WT and Fmr1 -/y mice recorded before (black and red, respectively) and after HFS (grey and pink, respectively). PTP magnitude measured 1 min after HFS and LTP measured 50–60 min post-HFS, both relative to baseline fEPSP slope. Proportion of mice exhibiting successful LTP induction, defined as a 50–60 min post-HFS slope >10% above baseline. PPR measured before and after HFS, and CV 2 analysis pre- and post-HFS responses. WT: n = 8 slices; Fmr1 -/y : n = 9 slices. (B) The same data, but shown for TA LTP recordings performed after 30 min incubation with the GABA A R antagonist gabazine (10 μM). WT: n = 7 mice; Fmr1 -/y : n = 10 mice. Data is shown as mean ± SEM or box-plots depicting 25%–75% range, maximum range; all with individual data points overlaid (open circles). Statistics shown from Mann-Whitney tests, Chi-squared tests, 2-way ANOVA or Wilcoxon signed-rank tests; ns-p > 0.05 (Mann-Whitney test); or ns p > 0.05, # - p < 0.05 (Wilcoxon signed-rank tests).

Article Snippet: GABA B R agonist baclofen (Bacl; 20 μM), mGluR1α antagonist LY367385 (LY; 20 μM), mGluR5 antagonist Fenobam (Feno; 10 μM), and GABA A R antagonist gabazine (10 μM) were dissolved in dH 2 O or DMSO and sourced from HelloBio (HelloBio Ltd., United Kingdom) or Tocris (Bio-Techne Ltd., United Kingdom).

Techniques: Incubation, MANN-WHITNEY

Journal: Frontiers in Pharmacology

Article Title: Elevated somatostatin interneuron long-term potentiation minimally regulates temporoammonic plasticity in a mouse model of Fragile X Syndrome

doi: 10.3389/fphar.2025.1640921

Figure Lengend Snippet: Summary of drug incubations on PTP and LTP magnitude post-HFS revealed no significant differences. (A) Post-HFS fEPSP slope (measured 0–1 min after stimulation) for PTP measured under control conditions and following application of baclofen (GABA B R agonist), gabazine (GABA A R antagonist), LY367385 (mGluR1α antagonist), Fenobam (mGluR5 antagonist), or s-DHPG (mGluR1/5 agonist); in wild-type (WT, black) and Fmr1 -/y (red) mice. (B) Data in the same form, but shown for LTP measured at 50–60 min post-HFS. All data shown as box-plots depicting 25%–75% range, maximum range; all with individual data points overlaid (open circles). Sample sizes (n = slices per group) are shown underneath. Statistics shown from 2-way ANOVA.

Article Snippet: GABA B R agonist baclofen (Bacl; 20 μM), mGluR1α antagonist LY367385 (LY; 20 μM), mGluR5 antagonist Fenobam (Feno; 10 μM), and GABA A R antagonist gabazine (10 μM) were dissolved in dH 2 O or DMSO and sourced from HelloBio (HelloBio Ltd., United Kingdom) or Tocris (Bio-Techne Ltd., United Kingdom).

Techniques: Control