Fallah, Michel1 ; Udobi, Kenea1 ; Swiatek, Aleksandra1 ; Scott, Chelsea1 ; Evans, Rebekah 1

Research facility: Georgetown University Medical Center

Published Aug 19, 2025 on Dryad. https://doi.org/10.5061/dryad.gf1vhhn1x

The canonical basal ganglia model predicts that the substantia nigra pars reticulata (SNr) and the globus pallidus externa (GPe) will have specific effects on locomotion: the SNr inhibiting locomotion and the GPe enhancing it. In this manuscript, we use in vivo optogenetics to show that a projection-defined neural subpopulation within each structure exerts non-canonical effects on locomotion. These non-canonical subpopulations are defined by their projection to the pedunculopontine nucleus (PPN) and mediate opposing effects on reward. To understand how these structures differentially modulate the PPN, we use ex vivo whole-cell recording with optogenetics to comprehensively dissect the SNr and GPe connections to regionally- and molecularly-defined populations of PPN neurons. The SNr inhibits all PPN subtypes, but most strongly inhibits caudal glutamatergic neurons. The GPe selectively inhibits caudal glutamatergic and GABAergic neurons, avoiding both cholinergic and rostral cells. This circuit characterization reveals non-canonical basal ganglia pathways for locomotion and valence.

Dataset DOI: 10.5061/dryad.gf1vhhn1x

Description of the data and file structure

These data are from our electrophysiology and behavioral experiments for Fallah et al., 2025 published in eLife.

Electrophysiology data are csv with data from Figures 2-6.

Behavior data with optogenetic activation is in csv files and shows data points used in Figure 7.

Files and variables

Files and variables

File: Figure2E_H.csv

Description: Raw and normalized current amplitude by stimulation number for ChAT+ PPN neurons in response to substantia nigra reticulata axon activation.

Variables

Columns are individual cells from rostral or caudal PPN and are the raw current amplitude and normalized current amplitude as specified.
Rows are current responses from individual pulses in the pulse train (20 Hz, 2 ms blue led light activations of SNr axons).

File: Figure2F_I.csv

Description: Raw measure of current amplitude during the first stimulation pulse and calculated paired pulse ratio between the first two current amplitudes of the 20 Hz stimulation train measured in ChAT+ PPN neurons in response to substantia nigra reticulata axon activation.

Variables

Columns are the raw measure of current amplitude during the first stimulation pulse and calculated paired pulse ratio (PPR) as specified.
Rows are individual cells from rostral or caudal ChAT+ PPN neurons.

File: Figure2K.csv

Description: Percent of pre-optical stimulation firing frequency in ChAT+ PPN neurons before, during, and after activation of substantia nigra reticulata axons.

Variables

Columns are the percent of pre-optical stimulation firing frequency (% Pre-Opto Frq) pre, during, and post optical stimulation.
Rows are individual cells from rostral or caudal ChAT+ PPN neurons.

File: Figure2L_M.csv

Description: Absolute change in firing frequency during optical stimulation of SNr axons, absolute change in rebound frequency during optical stimulation of SNr axons, and average resting membrane potential measured in ChAT+ PPN neurons.

Variables

Columns are the absolute change in firing frequency (dFrq During Opto), absolute change in rebound frequency (dRebFrq), and average resting membrane potential (Avg Rm). Values are not matched across rows.
Rows are individual cells from rostral or caudal ChAT+ PPN neurons.

File: Figure2N_O.csv

Description: Matched values for current amplitude during the first stimulation pulse, calculated paired pulse ratio, absolute change in firing frequency, pre-optical firing frequency, and change in rebound frequency in ChAT+ PPN neurons in response to substantia nigra reticulata axon activation.

Variables

Columns are the current amplitude during the first stimulation pulse (First oIPSC), calculated paired pulse ratio (PPR), absolute change in firing frequency (dFrq), pre-optical firing frequency (Pre-Opto Frq), and change in rebound frequency (dRebFrq) from a single neuron.
Rows are individual cells from rostral or caudal ChAT+ PPN neurons.

File: Figure3C_F.csv

Description: Raw and normalized current amplitude by stimulation number for Vgat+ PPN neurons in response to substantia nigra reticulata axon activation.

Variables

Columns are individual cells from rostral or caudal PPN and are the raw current amplitude and normalized current amplitude as specified.
Rows are current responses from individual pulses in the pulse train (20 Hz, 2 ms blue led light activations of SNr axons).

File: Figure3D_G.csv

Description: Raw measure of current amplitude during the first stimulation pulse and calculated paired pulse ratio between the first two current amplitudes of the 20 Hz stimulation train measured in Vgat+ PPN neurons in response to substantia nigra reticulata axon activation.

Variables

Columns are the raw measure of current amplitude during the first stimulation pulse and calculated paired pulse ratio (PPR) as specified.
Rows are individual cells from rostral or caudal Vgat+ PPN neurons.

File: Figure3H.csv

Description: Percent of pre-optical stimulation firing frequency in Vgat+ PPN neurons before, during, and after activation of substantia nigra reticulata axons.

Variables

Columns are the percent of pre-optical stimulation firing frequency (% Pre-Opto Frq) pre, during, and post optical stimulation.
Rows are individual cells from rostral or caudal Vgat+ PPN neurons.

File: Figure3I.csv

Variables

Columns are the absolute change in firing frequency (dFrq During Opto), absolute change in rebound frequency (dRebFrq), and average resting membrane potential (Avg Rm). Values are not matched across rows.
Rows are individual cells from rostral or caudal Vgat+ PPN neurons.

File: Figure3J-L.csv

Description: Matched values for current amplitude during the first stimulation pulse, calculated paired pulse ratio, absolute change in firing frequency, and pre-optical firing frequency in Vgat+ PPN neurons in response to substantia nigra reticulata axon activation.

Variables

Columns are the current amplitude during the first stimulation pulse (First oIPSC), calculated paired pulse ratio (PPR), absolute change in firing frequency (dFrq), and pre-optical firing frequency (Pre-Opto Frq) from a single neuron.
Rows are individual cells from rostral or caudal Vgat+ PPN neurons.

File: Figure4C_F.csv

Description: Raw and normalized current amplitude by stimulation number for Vglut2+ PPN neurons in response to substantia nigra reticulata axon activation.

Variables

Columns are individual cells from rostral or caudal PPN and are the raw current amplitude and normalized current amplitude as specified.
Rows are current responses from individual pulses in the pulse train (20 Hz, 2 ms blue led light activations of SNr axons).

File: Figure4D_G.csv

Description: Raw measure of current amplitude during the first stimulation pulse and calculated paired pulse ratio between the first two current amplitudes of the 20 Hz stimulation train measured in Vglut2+ PPN neurons in response to substantia nigra reticulata axon activation.

Variables

Columns are the raw measure of current amplitude during the first stimulation pulse and calculated paired pulse ratio (PPR) as specified.
Rows are individual cells from rostral or caudal Vglut2+ PPN neurons.

File: Figure4I.csv

Description: Percent of pre-optical stimulation firing frequency in Vglut2+ PPN neurons before, during, and after activation of substantia nigra reticulata axons.

Variables

Columns are the percent of pre-optical stimulation firing frequency (% Pre-Opto Frq) pre, during, and post optical stimulation.
Rows are individual cells from rostral or caudal Vglut2+ PPN neurons.

File: Figure4J.csv

Variables

Columns are the absolute change in firing frequency (dFrq During Opto), absolute change in rebound frequency (dRebFrq), and average resting membrane potential (Avg Rm). Values are not matched across rows.
Rows are individual cells from rostral or caudal Vglut2+ PPN neurons.

File: Figure4L-P.csv

Description: Matched values for current amplitude during the first stimulation pulse, calculated paired pulse ratio, absolute change in firing frequency, and pre-optical firing frequency in Vglut2+ PPN neurons in response to substantia nigra reticulata axon activation.

Variables

Columns are the current amplitude during the first stimulation pulse (First oIPSC), calculated paired pulse ratio (PPR), absolute change in firing frequency (dFrq), and pre-optical firing frequency (Pre-Opto Frq) from a single neuron.
Rows are individual cells from rostral or caudal Vglut2+ PPN neurons.

File: Figure6D_F.csv

Description: Raw and normalized current amplitude by stimulation number for ChAT+, Vglut2+, and Vgat+ caudal PPN neurons in response to globus pallidus externa axon activation.

Variables

Columns are individual cells from ChAT+, Vglut2+, or Vgat+ caudal PPN and are the raw current amplitude and normalized current amplitude as specified.
Rows are current responses from individual pulses in the pulse train (20 Hz, 2 ms blue led light activations of GPe axons).

File: Figure6E_G.csv

Description: Raw measure of current amplitude during the first stimulation pulse and calculated paired pulse ratio between the first two current amplitudes of the 20 Hz stimulation train measured in ChAT+, Vglut2+, and Vgat+ caudal PPN neurons in response to globus pallidus externa axon activation.

Variables

Columns are the raw measure of current amplitude during the first stimulation pulse and calculated paired pulse ratio (PPR) as specified.
Rows are individual cells from ChAT+, Vglut2+, or Vgat+ caudal PPN neurons.

File: Figure6H.csv

Description: Percent of pre-optical stimulation firing frequency in ChAT+, Vglut2+, and Vgat+ caudal PPN neurons before, during, and after activation of globus pallidus externa axons.

Variables

Columns are the percent of pre-optical stimulation firing frequency (% Pre-Opto Frq) pre, during, and post optical stimulation.
Rows are individual cells from ChAT+, Vglut2+, or Vgat+ caudal PPN neurons.

File: Figure6I.csv

Description: Absolute change in firing frequency during optical stimulation of GPe axons, absolute change in rebound frequency during optical stimulation of GPe axons, and average resting membrane potential measured in ChAT+, Vglut2+, and Vgat+ caudal PPN neurons.

Variables

Columns are the absolute change in firing frequency (dFrq During Opto), absolute change in rebound frequency (dRebFrq), and average resting membrane potential (Avg Rm). Values are not matched across rows.
Rows are individual cells from ChAT+, Vglut2+, or Vgat+ caudal PPN neurons.

File: Figure6J_K.csv

Description: Matched values for current amplitude during the first stimulation pulse, calculated paired pulse ratio, absolute change in firing frequency, and pre-optical firing frequency in caudal Vgat+ PPN neurons in response to globus pallidus externa axon activation.

Variables

Columns are the current amplitude during the first stimulation pulse (First oIPSC), calculated paired pulse ratio (PPR), absolute change in firing frequency (dFrq), and pre-optical firing frequency (Pre-Opto Frq) from a single neuron.
Rows are individual cells from caudal Vgat+ PPN neurons.

File: Figure6L_M.csv

Description: Matched values for current amplitude during the first stimulation pulse, calculated paired pulse ratio, absolute change in firing frequency, and pre-optical firing frequency in caudal Vglut2+ PPN neurons in response to globus pallidus externa axon activation.

Variables

Columns are the current amplitude during the first stimulation pulse (First oIPSC), calculated paired pulse ratio (PPR), absolute change in firing frequency (dFrq), and pre-optical firing frequency (Pre-Opto Frq) from a single neuron.
Rows are individual cells from caudal Vglut2+ PPN neurons.

** **

File: Figure_7C.csv

Description: Distance traveled over time

SNr = Substantia nigra axon stimulation
GPe= Globus pallidus axon stimulation
Control=control virus (non-chr2) injected and light applied.

Variables

Distance (m) traveled during each 1-minute segment during a trial.
Data are in columns representing individual mice.

File: Figure_7D.csv

Description: distance (m) traveled during stimulation

Ctrl HP: control high power
SNr HP: Substantia nigra axon stimulation high power
GPe HP: Globus pallidus axon stimulation high power
SNr LP: Substantia nigra axon stimulation low power
GPe LP: Globus pallidus axon stimulation low power

Variables

Columns are conditions (described above)
Each cell is the average distance (m) traveled during optical stimulation for one mouse.

File: Figure_7F.csv

Description: Percent time spent in stimulated zone in 3-chamber Real Time Place Preference task

Variables

Columns are conditions (described above)
Each cell is the percent time spent in the optically stimulated zone for one mouse.

File: Figure_7G.csv

Description: Percent time spent in previously stimulated zone during 1st minute on day 2. Zone is NOT stimulated during this task.

Ctrl: control
SNr: Substantia nigra axon stimulation
GPe: Globus pallidus axon stimulation

Variables

Columns are conditions (described above)
Each cell is the percent time spent in the first minute of the zone that had previously been optically stimulated (the day before) for one mouse.

File: Figure_7_FigureSupplement1A_B.csv

Description: mouse speed (m/s) in 10 s increments before during and after stimulation.

Variables

Each column is the average data before, during, and after stimulation for 1 mouse. (SNr = substantia nigra axon stimulation; GPe=Globus pallidus axon stimulation)

File: Figure_7_FigureSupplement2B.csv

Description: Distance traveled during stimulation with high power optical stimulation.

SNr = wild type mouse injected with constitute ChR2 (same as SNr condition in main figures)

DAT-Cre = Dopamine transporter-cre mouse injected with cre-dependent ChR2

Variables

Columns are conditions (described above)
Each cell is the distance (m) traveled during optical stimulation for one mouse.

File: Figure_7_FigureSupplement2C.csv

Description: Distance traveled during stimulation during low power stimulation.

SNr = wild type mouse injected with constitute ChR2 (same as SNr condition in main figures)

DAT-Cre = Dopamine transporter-cre mouse injected with cre-dependent ChR2

Variables

Columns are conditions (described in Figure S3B)
Each cell is the distance (m) traveled during optical stimulation for one mouse.

File: Figure_7_FigureSupplement2E.csv

Description: Percent time spent in stimulated zone with high laser power stimulation

Variables

Columns are conditions (described in Figure S3B)
Each cell is the percent time spent in optically stimulated zone for one mouse.

File: Figure_7_FigureSupplement2F.csv

Description: Percent time spent in stimulated zone with low laser power.

Variables

Columns are conditions (described in Figure S3B)
Each cell is the percent time spent in optically stimulated zone for one mouse.

Data from: Inhibitory basal ganglia nuclei differentially innervate pedunculopontine nucleus subpopulations and evoke opposite motor and valence behaviors

Data files

Abstract

Description of the data and file structure

Files and variables

Data from: Inhibitory basal ganglia nuclei differentially innervate pedunculopontine nucleus subpopulations and evoke opposite motor and valence behaviors

Data files

Abstract

README: Data from: Inhibitory basal ganglia nuclei differentially innervate pedunculopontine nucleus subpopulations and evoke opposite motor and valence behaviors

Description of the data and file structure

Files and variables