Journal: iScience

Article Title: Melanocortin 4 receptor-expressing neurons in the lateral stripe of the striatum regulate affect and motor control

doi: 10.1016/j.isci.2025.112456

Figure Lengend Snippet: MC4R-LSS neurons are activated by aversive foot shocks in a D1-independent manner (A) Timeline of experiments. (B) Representative picture of GCaMP8m-expression and fiber placement in the lateral stripe of the striatum (LSS) of an MC4R-cre mouse. Fiber tract and anterior commissure (aca) marked with dashed line; LSS marked with arrow. LV, lateral ventricle. Scale bar 200 μm. (C) GCaMP8m signal measured with fiber photometry from MC4R-LSS neurons shows activation of MC4R-LSS neurons in response to aversive shocks, but not to the onset of the predictive tone cue. No change in neural activity was seen in response to shock omission in the fear test on day 2. Mean and SEM from 6 mice, 6 trials per mouse. (D) Heatmap of the data shown in (C) but split out per trial showing that the neural response is similar across all trials. Each row in the heatmap represents the mean from 6 mice. (E) Dopamine measurements from the LSS during the same behavioral paradigm as in (C). Dopamine is released in the LSS in response to both the aversive foot shocks and their predictive tone cues. No clear change in dopamine release was seen in response to shock omission in the fear test on day 2. Mean and SEM from 7 mice, 6 trials per mouse. (F) Heatmap of the data shown in (E) but split out per trial showing that the tone-induced dopamine release develops during the session. Each row in the heatmap represents the mean from 7 mice. (G) iGluSnFR-measurements of glutamate release onto D1-expressing neurons in the LSS during fear conditioning. Glutamate is released onto D1-expressing neurons in response to the aversive foot shock. A small release can be seen in response to the tone onset. Mean and SEM from 10 mice, 6 trials per mouse. (H) Heatmap of the data shown in (G), but split out per trial, showing that the shock-induced glutamate release is similar across trials and that the tone-induced release is developed within the session. Each row in the heatmap represents the mean from 10 mice. (I) Timeline of the crossover experiment testing if shock-induced activity of MC4R-LSS neurons is D1-dependent. (J) Group mean peri-event traces (± SEM) from the experiment shows a robust increase in neural activity in response to the foot shock after both saline-injection and pretreatment with the D1-antagonist SCH23390 (0.2 mg/kg; n = 7). (K) Mean peak size during the shock for each animal showing that SCH23390 does not affect the shock-induced neural response ( n = 7, paired two-tailed t-test). (L) Analysis of the inactivity time during the sessions showing that mice spend significantly more time inactive after SCH23390 injection compared to saline injection ( n = 11, paired two-tailed t-test). ∗∗∗ p < 0.001.

Article Snippet: Standard mouse operant conditioning chamber , Med Associates , ENV-307W.

Techniques: Expressing, Activation Assay, Activity Assay, Saline, Injection, Two Tailed Test