Journal: Cell Reports Medicine

Article Title: Role of dopamine in the development of impaired counterregulation and impaired awareness of hypoglycemia

doi: 10.1016/j.xcrm.2026.102710

Figure Lengend Snippet: Sympathoadrenal response and dopaminergic action with agonist bromocriptine (A–C) Recurrent BROMO administration in i.c.v. reduced food intake and BG response. (A) Schematic diagram of recurrent aCSF ( n = 7) or recurrent BROMO ( n = 7, 2 μg) for 3 days into i.c.v. (B) BG on day 4 following singular injection of INS (15 U/kg NPH) Groups were compared via two-way ANOVA. (C) Cumulative food intake after INS injection (∗ p < 0.005 RBROMO i.c.v. vs. RCSF i.c.v. + INS). Groups were compared via unpaired t test. Each bar represents the mean + SEM. (D–H) Recurrent BROMO administration in i.c.v. and effects on CRR. (D) Schematic diagram of recurrent aCSF ( n = 7) or recurrent BROMO ( n = 7, 2 μg) into i.c.v.. (E) BG during hyperinsulinemic-hypoglycemic clamp where BG is held at 40–45 mg/dL for 90 min. Groups were compared via two-way ANOVA. (F) Ginf. Rate during clamp (∗∗∗∗ p < 0.0001 vs. RBROMO). Groups were compared via unpaired t test. (G) Peak epinephrine concentrations at basal and hypoglycemia (∗ p < 0.005 RCSF vs. RBROMO). Groups were compared via two-way ANOVA. (H) Peak glucagon concentrations at basal and hypoglycemia (∗ p < 0.005 RCSF vs. RBROMO). Groups were compared via two-way ANOVA. Each bar represents the mean + SEM. (I) Dopaminergic gene expression in VTA. Relative gene product expression of COMT, DDC, DRD2, SLC6A3 in the ventral tegmental area following 3-day treatment with RS ( n = 6), RH ( n = 7), or RH + MET ( n = 6) (∗ p < 0.04 RS vs. RH + MET; # p < 0.04 RH vs. RH + MET). Groups were compared via one-way ANOVA. Each bar represents the mean + SEM. (J–O) Recurrent BROMO infusion in VTA effects on CRR. (J) Schematic diagram of recurrent aCSF ( n = 7) or recurrent BROMO (n = 7–9, 5 μg/day; infusion rate 0.1 μL/min). (K) BG concentration during hyperinsulinemic-hypoglycemic clamp, which held BG at 40–50 mg/dL for 90 min. Groups were compared via two-way ANOVA. (L) Ginf. rate during clamp (∗∗∗∗ p < 0.001 RCSF vs. RBROMO). Groups were compared via two-way ANOVA. (M) Peak epinephrine concentrations at basal and hypoglycemia (∗ p < 0.05 BROMO vs. SAL). Groups were analyzed via unpaired t test. (N) Relative gene expression of DRD2 in the ventral tegmental area following a 3-day treatment with either aCSF or BROMO directly into the VTA (∗ p < 0.05 aCSF vs. BROMO). Groups were compared via unpaired t test. (O) Relative gene expression of SLC6A3 in the ventral tegmental area following a 3-day treatment with either aCSF or BROMO directly into the VTA ( p = 0.21). Groups were compared via unpaired t test. Each bar represents the mean + SEM.

Article Snippet: In brief, total RNA was extracted and purified from brain regions using miRNeasy Mini Kit (Qiagen, CA) which was reverse transcribed and then amplified by real-time PCR using Taqman gene assays (Thermo Fisher) for dopamine receptor D2 ( Drd2 ; assay ID: Rn00561126_m1), dopamine transporter or solute carrier family 6, member 3 ( Dat or Slc6a3 ; assay ID: Rn00562224_m1), dopa decarboxylase ( Ddc : assay ID: Rn01401189_m1), catechol- O -methyltransferase ( Comt ; assay ID: Rn00561037_m1) and the housekeeping gene beta-actin ( Actb ; assay ID: Rn00667869_m1).

Techniques: Injection, Gene Expression, Expressing, Concentration Assay

Journal: iScience

Article Title: The role of dopamine-sensitive motor cortical circuits in the development and execution of skilled forelimb movements

doi: 10.1016/j.isci.2026.114983

Figure Lengend Snippet: Head-fixed mice learn to perform skilled forelimb movements to obtain a reward (A) Representation of injecting AAV9-hSyn-GRAB DA2h and AAV1-Syn-Flex-NES-jRGECO1a into M1. Coronal sections obtained from D1Cre and D2Cre mice showing expression of GRAB DA2h (green) and jRGECO1a (red) in the M1 forelimb area (brain slices are 0.5 mm anterior to the bregma). Scale bars, 500 μm. Magnification: 20×. See also for the histological map of GRAB DA2h and jRGECO1a expression and fiber tip placements. (B) Representation of the task in which head-fixed mice perform skilled forelimb movements with a joystick to obtain a delayed reward, and a fiber photometry setup for simultaneous recording of DA dynamics and population level Ca 2+ activity in the M1 forelimb area. See also for representative traces of neuronal Ca 2+ and DA signals acquired during training. (C) Increase in the number of rewarded joystick movements in D1Cre mice during training. (D) Movement kinematic parameters obtained from the early and late sessions in D1Cre mice showing that the average movement amplitude and velocity increased between training phases. (Left to right) Distribution of movement amplitudes, movement amplitude, and joystick velocity at the time of threshold crossing. (E) Individual movement trajectories of an example D1Cre mouse aligned to the initial joystick position (black dot), and preferred movement direction in the group of D1Cre animals (based on all extracted trajectories). (F) Change in movement similarity in D1Cre mice (based on the average distance between pairwise trajectories). (Left to right) Similarity between the early and late sessions; similarity within the late session. (G–J) Same as (C)–(F) for D2Cre mice. In (C)–(J), data were obtained from 14 D1Cre (10 Cre+ and 4 Cre-) and 13 D2Cre (10 Cre+ and 3 Cre-) animals. Data are represented as mean ± SEM. Paired t test; ∗∗∗ p < 0.001, ∗∗ p < 0.01, ∗ p < 0.05.

Article Snippet: D2Cre: B6.FVB(Cg)-Tg(Drd2-cre)ER44Gsat/Mmucd , MMRRC: UCD , RRID: MMRRC_032108-UCD.

Techniques: Expressing, Activity Assay

Journal: iScience

Article Title: The role of dopamine-sensitive motor cortical circuits in the development and execution of skilled forelimb movements

doi: 10.1016/j.isci.2026.114983

Figure Lengend Snippet: DA dynamics in the M1 encode execution of skilled forelimb movement and reward consumption (A) Peri-event plots of the average normalized DA signal in D1Cre mice aligned to threshold cross (top) and binned data analyzed at 1-s intervals (bottom). (Left to right) Data are presented as within-session (early or late) comparisons with respect to the baseline (BL) and between-session comparisons of movement- and reward-related periods (early vs. late). (B) Peri-event plots of the average normalized Ca 2+ signal in D1Cre mice aligned to threshold cross (top) and binned data analyzed at 1-s intervals (bottom). (Left to right) Data are presented as within-session (early or late) comparisons with respect to the BL and between-session comparisons of movement- and reward-related periods (early vs. late). (C) Peri-event plots of the average lick rate (licks/s) in D1Cre mice aligned to threshold cross (top) and binned data analyzed at 1-s intervals (bottom). (Left to right) Data are presented as within-session (early or late) comparisons with respect to the BL and between-session comparisons of movement- and reward-related periods (early vs. late). (D–F) Same as (A)–(C) for D2Cre mice. In (A)–(F), data were obtained from 14 D1Cre (10 Cre+ and 4 Cre-) and 13 D2Cre (10 Cre+ and 3 Cre-) animals. Data are represented as mean ± SEM. Repeated-measure one-way ANOVA; multiple comparisons: BL mean vs. every other mean, movement (0–1 s) mean vs. reward (1–2 s) mean; Bonferroni’s post hoc test; ∗∗∗ p < 0.001, ∗∗ p < 0.01, ∗ p < 0.05; or paired t test; ∗∗∗ p < 0.001, ∗∗ p < 0.01, ∗ p < 0.05. Dashed lines indicate joystick movement (threshold crossing) and reward delivery. See also for comparisons between D1Cre and D2Cre mice and cross-correlations between DA and Ca 2+ signals.

Article Snippet: D2Cre: B6.FVB(Cg)-Tg(Drd2-cre)ER44Gsat/Mmucd , MMRRC: UCD , RRID: MMRRC_032108-UCD.

Techniques:

Journal: iScience

Article Title: The role of dopamine-sensitive motor cortical circuits in the development and execution of skilled forelimb movements

doi: 10.1016/j.isci.2026.114983

Figure Lengend Snippet: The neural response in the M1 reflects the movement vigor (A and B) Movement kinematic parameters obtained from the low- and high-amplitude trials during regular threshold session in D1Cre and D2Cre mice showing the difference in response vigor. (Left to right) Distribution of movement amplitudes, movement amplitude, and joystick velocity at the time of threshold crossing. (C) Peri-event plots of the average normalized DA signal in D1Cre mice aligned to threshold cross (top) and comparisons of movement- and reward-related periods (analyzed at 1-s intervals) between low- and high-amplitude trials (bottom). (D) Peri-event plots of the average normalized Ca 2+ signal in D1Cre mice aligned to threshold cross (top) and comparisons of movement- and reward-related periods (analyzed at 1-s intervals) between low- and high-amplitude trials (bottom). (E) Peri-event plots of the average lick rate (licks/s) in D1Cre mice aligned to threshold cross (top) and comparisons of movement- and reward-related periods (analyzed at 1-s intervals) between low and high amplitude trials (bottom). (F–H) Same as (C)–(E) for D2Cre mice. In (A)–(H), data were obtained from 14 D1Cre (10 Cre+ and 4 Cre-) and 13 D2Cre (10 Cre+ and 3 Cre-) animals. Data are represented as mean ± SEM. Paired t test; ∗∗∗ p < 0.001, ∗∗ p < 0.01, ∗ p < 0.05. Dashed lines indicate joystick movement (threshold crossing) and reward delivery. See also for comparisons between D1Cre and D2Cre mice.

Article Snippet: D2Cre: B6.FVB(Cg)-Tg(Drd2-cre)ER44Gsat/Mmucd , MMRRC: UCD , RRID: MMRRC_032108-UCD.

Techniques:

Journal: iScience

Article Title: The role of dopamine-sensitive motor cortical circuits in the development and execution of skilled forelimb movements

doi: 10.1016/j.isci.2026.114983

Figure Lengend Snippet: The neural response in the M1 reflects the movement vigor during the increased threshold session (A and B) Movement kinematic parameters obtained from the low- and high-amplitude trials during the increased threshold session in D1Cre and D2Cre mice. (Left to right) Distribution of movement amplitudes, movement amplitude, and joystick velocity at the time of threshold crossing. (C) Peri-event plots of the average normalized DA signal in D1Cre mice aligned to threshold cross (top) and comparisons of movement- and reward-related periods (analyzed at 1-s intervals) between low- and high-amplitude trials (bottom). (D) Peri-event plots of the average normalized Ca 2+ signaling D1Cre mice aligned to threshold cross (top) and comparisons of movement- and reward-related periods (analyzed at 1-s intervals) between low- and high-amplitude trials (bottom). (E) Peri-event plots of the average lick rate (licks/s) in D1Cre mice aligned to threshold cross (top) and comparisons of movement- and reward-related periods (analyzed at 1-s intervals) between low- and high-amplitude trials (bottom). (F–H) Same as (C)–(E) for D2Cre mice. In (A)–(H) Data were obtained from 14 D1Cre (10 Cre+ and 4 Cre-), and 12 D2Cre (10 Cre+ and 2 Cre-) animals. Data are represented as mean ± SEM. Paired t test; ∗∗∗ p < 0.001, ∗∗ p < 0.01, ∗ p < 0.05. Dashed lines indicate joystick movement (threshold crossing) and reward delivery. See also for comparisons between D1Cre and D2Cre mice.

Article Snippet: D2Cre: B6.FVB(Cg)-Tg(Drd2-cre)ER44Gsat/Mmucd , MMRRC: UCD , RRID: MMRRC_032108-UCD.

Techniques:

Journal: iScience

Article Title: The role of dopamine-sensitive motor cortical circuits in the development and execution of skilled forelimb movements

doi: 10.1016/j.isci.2026.114983

Figure Lengend Snippet: DA in the M1 signals actual reward availability during skilled performance (A) Peri-event plots of the average normalized DA signal in D1Cre mice aligned to threshold cross (top) and binned data analyzed at 1-s intervals (bottom). (Left to right) Data are presented as within-session (delay or omission) comparisons with respect to the baseline (BL). (B) Peri-event plots of the average normalized Ca 2+ signal in D1Cre mice aligned to threshold cross (top) and binned data analyzed at 1-s intervals (bottom). (Left to right) Data are presented as within-session (delay or omission) comparisons with respect to the BL. (C) Peri-event plots of the average lick rate (licks/s) in D1Cre mice aligned to threshold cross (top) and binned data analyzed at 1-s intervals (bottom). (Left to right) Data are presented as within-session (delay or omission) comparisons with respect to the BL. (D–F) Same as (A)–(C) for D2Cre mice. In (A)–(F), data for “delayed reward” analysis were obtained from 14 D1Cre (10 Cre+ and 4 Cre-) and 13 D2Cre (10 Cre+ and 3 Cre-) animals and for “omission” analysis from 9 D1Cre (7 Cre+ and 2 Cre-) and 8 D2Cre (8 Cre+) animals. Data are represented as mean ± SEM. Repeated-measure one-way ANOVA; multiple comparisons: BL mean vs. every other mean, movement (0–1 s) mean vs. expected reward (1–2 s) mean, expected reward (1–2 s) mean vs. actual reward (3–4 s) mean; Bonferroni’s post hoc test; ∗∗∗ p < 0.001, ∗∗ p < 0.01, ∗ p < 0.05 See also for comparisons between D1Cre and D2Cre mice.

Article Snippet: D2Cre: B6.FVB(Cg)-Tg(Drd2-cre)ER44Gsat/Mmucd , MMRRC: UCD , RRID: MMRRC_032108-UCD.

Techniques:

Journal: iScience

Article Title: The role of dopamine-sensitive motor cortical circuits in the development and execution of skilled forelimb movements

doi: 10.1016/j.isci.2026.114983

Figure Lengend Snippet: A subset of D1+ and D2+ neurons of the M1 contacts long-range targets (A) Representation of the four major areas of rAAV2-Retro-EYFP and Fluoro-Green injections: primary motor cortex (M1), dorsolateral striatum (DLS), thalamus (Thal), and pontine nucleus (PN). See also for representative histology of the injection sites. (B and C) Coronal sections obtained from D1-tdTomato and D2Cre::Ai14 (tdTomato) mice showing laminar distribution of tdTomato (red) expressing D1+ or D2+ neurons and EYFP or FGr (green) expressing retrogradely labeled projection neurons in the M1 forelimb area (brain slices are 0.5 mm anterior to the bregma). Scale bars, 50 μm. See also for analysis of laminar distributions. (D) Cell density of D1+ neurons plotted as a function of distance from pia (where pia = 0 and white matter = 1; therefore, <0.5 indicates cells clustered in the upper layers, while >0.5 indicates cells clustered in the deep layers). (E) Colocalization of D1+ neurons with different populations of projection neurons. Percentage of D1+ neurons indicates colabeled cells across all layers that are also EYFP+ (% [D1+ EYFP+] / D1+) or FGr+ (% [D1+ FGr+] / D1+). Percentage of EYFP+ neurons indicates cells that are also D1+ (% [D1+ EYFP+] / EYFP+), and percentage of FGr+ neurons indicates cells that are D1+ (% [D1+ FGr+] / FGr+). (F) Comparison of labeling specificity of rAAV2-retro and FGr tracers measured by the number of cells labeled by each tracer. (G–I) Same as (D)–(F) for D2Cre mice. In (D)–(I), data were obtained from 21 D1-tdTomato and 19 D2Cre::Ai14 animals (2–3 mice per injection site, 4 slices per animal, slices were collected from −0.10 mm posterior to 1.00 mm anterior to the bregma). Data are represented as mean ± SEM. Paired t test; ∗∗∗ p < 0.001. Two-way ANOVA; multiple comparisons: EYFP mean vs. FGr mean; Bonferroni’s post hoc test; ∗∗∗ p < 0.001, ∗∗ p < 0.01. (B–I) cM1 (primary motor cortex injection, M1 forelimb area contralateral to the injection site); cDLS (DLS injection, M1 forelimb area contralateral to the injection site); iDLS (dorsolateral striatum injection, M1 forelimb area ipsilateral to the injection site); iThal (thalmus injection, M1 forelimb area ipsilateral to the injection site); iPN (pontine nucleus injection, M1 forelimb area ipsilateral to the injection site).

Article Snippet: D2Cre: B6.FVB(Cg)-Tg(Drd2-cre)ER44Gsat/Mmucd , MMRRC: UCD , RRID: MMRRC_032108-UCD.

Techniques: Injection, Expressing, Labeling, Comparison

Journal: bioRxiv

Article Title: Enkephalin Gates D2-MSN Disinhibition of the Ventral Pallidum During Cocaine Abstinence

doi: 10.64898/2026.03.11.711212

Figure Lengend Snippet: (A) Cocaine abstinence does not alter mRNA abundance for the dopamine D2 receptor gene ( Drd2 ) in D2-PenkKOs (saline, n = 7; cocaine, n = 7) or littermate Penk f/f controls (saline, n = 10; cocaine, n = 10). (B, D) Example traces of optogenetically-evoked inhibitory post synaptic currents (oIPSC) originating from D2-MSN and recorded in D1-MSNs. Adora2a-Cre controls (B) and D2-PenkKOs (D) were 14 days abstinent from repeated saline or cocaine at the time of recording. (C, E) Quinpirole dose-dependently inhibited oIPSC amplitude in Adora2a-Cre controls (saline: 18 cells/7 mice, cocaine: 13 cells/6 mice) and D2-PenkKOs (saline: 8 cells/3 mice, cocaine: 7 cells/3 mice) (Quinpirole x Cocaine interaction, p < 0.0001). However, quinpirole was less effective at suppressing oIPSCs in cocaine-abstinent mice than the saline-abstinent group. Asterisks represent post-hoc t-tests comparing saline versus cocaine groups and were collapsed across genotype. * p < 0.05: saline vs. cocaine for 0.25 and 0.5 µM. ** p < 0.01: saline vs. cocaine for 1 µM. Data are shown as mean ± SEM, with individual data points labeled as male (circles) and females (triangles).

Article Snippet: Relative mRNA abundance of proenkephalin ( Penk , Mm01212875_m1), dopamine D2 receptor ( Drd2 , Mm00438541_m1), and β-actin ( Actb, Mm01205647_g1) were determined with TaqMan Gene Expression Assay using a CFX384 Real-Time System (initial hold at 95 °C for 20 sec, 40 cycles at 95 °C for 1 sec, and 60 °C for 20 sec).

Techniques: Saline, Labeling