Multiple dynamic interactions from basal ganglia direct and indirect pathways mediate action selection
- Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, United States
- Center for Motor Control and Disease, Key Laboratory of Brain Functional Genomics, East China Normal University, China
- NYU–ECNU Institute of Brain and Cognitive Science, New York University Shanghai, China
Figures
Figure 1 with 3 supplements
The neuronal dynamics in substantia nigra pars reticulata (SNr) during the 2–8 s action selection task.
(A) Schematic diagram for the design of 2–8 s task. (B) Correct rate for wild-type mice across 14 days’ training (n=10 mice, one-way repeated-measures ANOVA, significant effect of training days, F13,…
Figure 1—figure supplement 1
Behavioral performance across 14 days of training and the substantia nigra pars reticulata (SNr) neuronal recording on day 1.
(A) Lever press latency after lever extension for wild-type mice across 14 days’ training (n=10 mice, one-way repeated-measures ANOVA, effect of training days, F13,117=21.32, p<0.0001). (B) Lever …
Figure 1—figure supplement 2
Examples of substantia nigra pars reticulata (SNr) neuron and spiny projection neuron (SPN) subtypes.
(A–D) Firing activities of example SNr neurons of Type 1 (A), Type 2 (B), Type 3 (C), and Type 4 (D) in correct 8 s trials after 14 days training. Top panels: Raster plot of spikes across trials …
Figure 1—figure supplement 3
Substantia nigra pars reticulata (SNr) neuron activities in left and right hemisphere.
(A) Firing rate index (FRI) of neuronal activity for all task-related SNr neurons in correct 8 s trials recorded in the left hemisphere. The magnitude of FRI is color coded and the SNr neurons are …
Figure 2 with 1 supplement
Substantia nigra pars reticulata (SNr) neuronal dynamics reflect action selection but not interval time or reward value.
(A) Task diagram of 2–8 s control task with 10% 16 s probe trials. (B) Percentage of behavioral choice in 2 s, 8 s, and 16 s trials (blue: left choice; red: right choice) (n=9 mice, paired t-test, p<…
Figure 2—figure supplement 1
Behavioral statistics and neuronal dynamics of substantia nigra pars reticulata (SNr) neurons in the standard and reversed 2–8 s tasks.
(A) Correct rates of the same group of mice both in the standard and reversed 2–8 s tasks (n=6 mice, paired t-test, p=0.33). (B) Lever press ratios of the same group of mice both in the standard and …
Figure 3 with 2 supplements
Neuronal activity of striatal D1- and D2-expressing spiny projection neurons (D1- and D2-SPNs) during action selection.
(A) Firing rate index (FRI) of neuronal activity for all task-related SPNs in correct 8 s trials. SPNs were classified as Types 1–4. (B–E) Averaged FRI for Type 1 (B), Type 2 (C), Type 3 (D), Type 4 …
Figure 3—figure supplement 1
Striatum neuronal recording on day 1 of training, recording array, and optic fiber placement validation.
(A) Averaged FRI for Type 1, Type 2, Type 3, and Type 4 of spiny projection neurons (SPNs) in correct (red) and incorrect 2 s trials (gray). (B) Firing rate index (FRI) of neuronal activity for all …
Figure 3—figure supplement 2
Striatal projection neuron activities in left and right hemisphere.
(A) Firing rate index (FRI) of neuronal activity for all task-related spiny projection neurons (SPNs) in correct 8 s trials recorded in the left hemisphere. The magnitude of FRI is color coded and …
Figure 4 with 1 supplement
Selective genetic knockout and ablation of D1- or D2-expressing spiny projection neurons (D1- or D2-SPNs) distinctly alters action selection.
(A) Correct rate of control (n=11 mice) and D1-NR1 KO mice (n=16) in 2–8 s task during 14 days’ training (two-way repeated-measures ANOVA, significant difference between control and KO mice, F1,25=10…
Figure 4—figure supplement 1
Simulation of lesion experiments in Go/No-Go, Co-activation, and combination models.
(A) Diagram of Go/No-Go model. (B) The psychometric curves of behavior outputs simulated by Go/No-Go model in control (black) and D1-expressing spiny projection neurons (D1-SPNs) ablation condition …
Figure 5 with 1 supplement
Optogenetic manipulation of D1- vs. D2-expressing spiny projection neurons (D1- vs. D2-SPNs) differently regulates action selection.
(A) Schematic of optic fiber implantation for experimentally optogenetic excitation or inhibition of D1- or D2-SPNs in the dorsal striatum. (B, C) Schematic for optogenetic excitation (B) and …
Figure 5—figure supplement 1
Simulation of optogenetic manipulation in Go/No-Go and Co-activation models.
(A, B) Simulating optogenetic activation (A) and inhibition (B) of D1-expressing spiny projection neurons (D1-SPNs) at 2 s. Blue bar above indicates optogenetic activation. Yellow bar above …
Figure 6 with 3 supplements
A Triple-control computational model of basal ganglia direct and indirect pathways for action selection.
(A) Network structure of the cortico-basal ganglia model based on realistic anatomy and synaptic connectivity. Dashed lines indicate multi-synaptic connections. (B) Schematic of …
Figure 6—figure supplement 1
The neuronal activities in the ‘Triple-control’ model and simulation of lesion experiments.
(A) The simulated neuronal dynamics quantified as firing rate index (FRI) for the cortical neurons in 8 s trials. (B) The simulated neuronal dynamics quantified as FRI for the D1-expressing spiny …
Figure 6—figure supplement 2
Optogenetic activation of D1- vs. D2-expressing spiny projection neurons (D1- vs. D2-SPNs) differently regulates substantia nigra pars reticulata (SNr) activities in model and experiments.
(A) A computational motif of indirect pathway with collateral inhibitory synapse D2-SPN 1→ D2-SPN 2. The collateral synapse between D2-SPNs exhibits short-term depression. (B) Relationship between …
Figure 6—figure supplement 3
Computational modeling of optogenetic manipulation reveals that D1- vs. D2-expressing spiny projection neurons (D1- vs. D2-SPNs) differently regulates substantia nigra pars reticulata (SNr) outputs in the ‘Triple-control’ model.
(A, B) Schematic for optogenetic manipulation of D1-SPNs (A) and D2-SPNs (B) in the ‘Triple-control’ model. (C) Modeling of neuronal dynamics of SNr Type 1/Type 2 (left panel) and net output (right …
Figure 7 with 3 supplements
Computational modeling reveals direct and indirect pathways regulating action selection in a distinct manner.
(A) Schematic for manipulation of D1-expressing spiny projection neurons (D1-SPNs) in ‘Triple-control’ model. (B) Schematic of manipulation of D1-SPNs in the center-surround-context receptive field …
Figure 7—figure supplement 1
Computational modeling of manipulation reveals that Go/No-Go and Co-activation model differently predicts the behavioral outcomes.
(A) Diagram of Go/No-Go model. (B) Diagram of Co-activation model. (C) Correct rate change in 2 s (left panel) and 8 s trials (right panel) when manipulating D1-expressing spiny projection neurons …
Figure 7—figure supplement 2
Computational modeling reveals that the linear and nonlinear modulation of action selection by direct versus indirect pathway qualitatively hold with additional striatal collateral connections.
(A) Schematic for ‘Triple-control’ model with D1-D1 collateral connections. (B) Correct rate change in 2 s trials (upper panel) and 8 s trials (bottom panel) when manipulating D1-expressing spiny …
Figure 7—figure supplement 3
Computational modeling of dopaminergic modulation in the ‘Triple-control’ model.
(A) Diagram of Triple-control model with dopaminergic modulation on spiny projection neurons (SPNs). (B) Schematic of center-surround-context receptive field diagram with dopaminergic modulation …
Videos
Video 1
Stereotypical behavior of a well-trained mouse in a successful 8 s trial.
Tables
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers | Additional information |
|---|---|---|---|---|
| Strain, strain background (adeno-associated virus) | AAV9-FLEX-DTR-GFP | Salk GT3 Core | N/A | |
| Strain, strain background (adeno-associated virus) | AAV5-EF1a-DIO-hChR2(H134R)-mCherry | University of North Carolina Vector Core | N/A | |
| Strain, strain background (adeno-associated virus) | AAV9-EF1a-DIO-hChR2(H134R)-eYFP | University of Pennsylvania Vector Core | Cat# AV-9-20298P | |
| Strain, strain background (adeno-associated virus) | AAV5-EF1a-DIO-eNpHR3.0-eYFP | University of North Carolina Vector Core | N/A | |
| Chemical compound, drug | Muscimol, GABAA receptor agonist | Sigma-Aldrich | Cat# M1523 | |
| Chemical compound, drug | Diphtheria toxin | List Biological Labs | Part# 150 | |
| Strain, strain background (Mus musculus) | Mouse: C57BL/6 | Envigo/Harlan | Code: 044 | |
| Strain, strain background (Mus musculus) | Mouse: NR1f/f (B6.129S4-Grin1tm2Stl/J) | Jackson Laboratory | Stock# 005246 | |
| Strain, strain background (Mus musculus) | Mouse: Ai32 (B6;129S-Gt(ROSA)26Sortm32(CAG-COP4*H134R/EYFP)Hze/J) | Jackson Laboratory | Stock# 012569 | |
| Strain, strain background (Mus musculus) | Mouse: D1-cre (B6.FVB(Cg)-Tg(Drd1a-cre)EY217Gsat/Mmucd) | MMRRC | RRID: MMRRC_034258-UCD | |
| Strain, strain background (Mus musculus) | Mouse: A2a-cre (B6.FVB(Cg)-Tg(Adora2a-cre)KG139Gsat/Mmucd) | MMRRC | RRID: MMRRC_036158-UCD | |
| Software, algorithm | GraphPad Prism | GraphPad Software | Version 7.03 | https://www.graphpad.com/scientific-software/prism/ |
| Software, algorithm | MATLAB | MathWorks | R2013a | https://www.mathworks.com/products/matlab.html |
| Software, algorithm | Med-PC | Med Associates | Cat# SOF-735 | https://med-associates.com/product/med-pc-v/ |
| Software, algorithm | Offline Sorter | Plexon | Version 3.3.3 | https://plexon.com/products/offline-sorter/ |
| Software, algorithm | OmniPlex | Plexon | Version 1.4.5 | https://plexon.com/products/omniplex-software/ |
| Software, algorithm | EthoVision | Noldus | Version 8.5 | |
| Other | Med Associates operant chamber | Med Associates | Cat# MED-307W-D1 | |
| Other | Electrode Array | Innovative Neurophysiology | N/A | |
| Other | 473 nm laser | LaserGlow Technologies | N/A | |
| Other | 532 nm laser | LaserGlow Technologies | N/A |
