Journal: iScience
Article Title: Cannabinoid overrides triggers of GABAergic plasticity in vestibular circuits and distorts the development of navigation
doi: 10.1016/j.isci.2025.112566
Figure Lengend Snippet: eCB release is triggered by 5-HT and CCK receptors but not metabotropic glutamate receptors in developing VN neurons (A 1 ) With the bath addition of MDL11939 (a 5-HT receptor antagonist) to P5-8 brain slices, the percentage of P5–8 MVN neurons showing LTD GABA decreased to 30% (green triangles, p = 0.003), contrasting 79% in controls. (A 2 ) With the bath addition of CI988 (a CCKBR antagonist) the percentage of P5–8 MVN neurons showing LTD GABA decrease slightly to 50% (CI988, blue triangles), but was not statistically significant ( p = 0.096). (A 3 ) With the bath addition of LY367385 (a mGLuR1 receptor antagonist, black circles) or MPEP (a mGluR5 antagonist, pink triangles), the percentage of P5–8 MVN neurons showing LTD GABA was similar to the control ( LY367385 : 73%, p = 1; MPEP: 62%, p = 0.347). (A 4 ) Bar charts summarizing the individual PSC GABA (top) and the percentages (bottom) of P5-8 MVN neurons showing each type of response (LTD, light gray; LTP, white; no change, dark gray) in each treatment group after TBS. (B 1 ) In P9–11 brain slices, no LTD or LTP was observed in the averaged response of recorded MVN cells (green circles). This was in agreement with the majority (61%) of cells showing no change after TBS (see B 4 ). With the bath addition of α-m-5-HT (a 5-HT receptor agonist), the percentage of MVN neurons showing LTD GABA after an initial TBS increased to 78% (yellow triangles, p < 0.001). These LTD GABA -expressing cells could not respond to a second TBS with further LTD GABA with the addition of Orlistat to the bath. (B 2 ) With the bath addition of CCK (a CCKBR agonist), 57% of the P9–11 MVN neurons showed LTD GABA (purple triangles, p = 0.011), contrasting control rats in which only 11% of sampled MVN neurons showed LTD GABA . (B 3 ) With the bath addition of DHPG (a mGluR1 agonist), the percentage of MVN neurons showing LTD GABA after TBS did not change significantly (27%, blue circles, p = 0.484). (B 4 ) Bar charts summarizing the individual PSC GABA (top) and the percentages (bottom) of P9–11 MVN neurons in each treatment group after TBS. Mean ± SEM are shown. Fisher’s exact test with Bonferroni’s correction for multiple measurements was used to evaluate change in responses to TBS in (A 4 ) and (B 4 ).
Article Snippet: LY367385 ((S)-(+)-α-Amino-4-carboxy-2-methylbenzeneacetic acid), DHPG (RS)-3,5-dihydroxyphenylglycine , Tocris Bioscience 1237/10 , .
Techniques: Control, Expressing