Data from: Dopamine subsystems that track internal states
Data files
Jan 07, 2026 version files 135.63 MB
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figure1.xlsx
134.95 MB
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figure2.xlsx
340.71 KB
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figure3.xlsx
42.58 KB
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figure4.xlsx
268.19 KB
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figure5.xlsx
15.28 KB
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README.md
9.88 KB
Abstract
Food and water are rewarding in part because they satisfy our internal needs. Dopaminergic neurons in the ventral tegmental area (VTA) are activated by gustatory rewards, but how animals learn to associate these oral cues with the delayed physiological effects of ingestion is unknown. Here, we show that individual dopaminergic neurons in the VTA respond to the detection of nutrients or water at specific stages of ingestion. A major subset of dopaminergic neurons tracks changes in systemic hydration that occur tens of minutes after thirsty mice drink water, whereas different dopaminergic neurons respond to nutrients in the gastrointestinal tract. We show that information about fluid balance is transmitted to the VTA by a hypothalamic pathway and then rerouted to downstream circuits that track the oral, gastrointestinal, and post-absorptive stages of ingestion. To investigate the function of these signals, we used a paradigm in which a fluid’s oral and post-absorptive effects can be independently manipulated and temporally separated. We show that mice rapidly learn to prefer one fluid over another based solely on its rehydrating ability and that this post-ingestive learning is prevented if dopaminergic neurons in the VTA are selectively silenced after consumption. These findings reveal that the midbrain dopamine system contains subsystems that track different modalities and stages of ingestion, on timescales from seconds to tens of minutes, and that this information is used to drive learning about the consequences of ingestion.
Dataset DOI: 10.5061/dryad.zgmsbccsf
Description of the data and file structure
This dataset contains data from the published paper titled "Dopamine subsystems that track internal states" published by Grove et al., in Nature, 2022. This article can be accessed here: https://www.nature.com/articles/s41586-022-04954-0. We have submitted the raw data for this manuscript, with each file containing the data necessary to replicate the graphs in each main figure. Each sheet contains data separated by subfigure, and, where relevant, by graphs within that subfigure. The top row of each sheet contains additional information about the data structure.
This dataset contains the data underlying the main figures presented in Grove et al., 2022. Data are provided as Microsoft Excel (.xlsx) files, where each file corresponds to a primary figure in the manuscript, and individual worksheets represent the data used to generate each subfigure (e.g. Fig. 1a). Submission of this dataset is intended to ensure transparency and reproducibility of the results, and the data herein made be reused for secondary analysis.
Full methods can be obtained online here: https://www.nature.com/articles/s41586-022-04954-0#Sec8
Files and variables
File: figure1.xlsx
-fig1bcd_waterlicks_heatmap: z-scored activity of individual ventral tegmental dopamine (VTA-DA) cells (y) by time (x) in 4 Hz increments during water access (first lick at x=2400, or 10min)
-fig1d_waterig_heatmap: z-scored activity of individual VTA-DA cells (y) by time (x) in 4 Hz increments during water intragastric (IG) infusion (IG from x=2400 to x=5280)
-fig1d_waterip_heatmap: z-scored activity of individual VTA-DA cells (y) by time (x) in 4 Hz increments during water intraperitoneal (IP) injection (IP given at x=2400)
-fig1d_saltip_heatmap: z-scored activity of individual VTA-DA cells (y) by time (x) in 4 Hz increments during 3M sodium chloride (NaCl) IP injection (IP given at x=2400)
-fig1e_licks_postingestion: z-scored activity during post-ingestive time window following consumption of water, 300mM NaCl, and Ensure
-fig1e_postig: z-scored activity following IG infusion of water, 300mM NaCl, and Ensure
-fig1e_ip: z-scored activity following IP injection of water, 3M NaCl, isoproterenol (isop), and polyethylene glycol (PEG)
-fig1f_longig_heatmap: z-scored activity of individual IG-activated VTA-DA cells (y) by time (x) in 4 Hz increments during water IG infusion (IG from x=2400 to x= 1280)
-fig1f_longig_trace: average z-scored activity trace of IG-activated VTA-DA cells during water IG infusion (IG from 10 min to 16 min). Time is shown in 0.8Hz increments, dff refers to mean z-scored activity, se refers to standard error of that activity
-fig1g_water_trace: average z-scored activity trace of IP-activated VTA-DA cells during water IP injection (IP given at x=600). Time is shown in 1Hz increments, dff refers to mean z-scored activity, se refers to standard error of that activity
-fig1g_salt_trace: average z-scored activity trace of IP-inhibited VTA-DA cells during 3M NaCl IP injection (IP given at x=600). Time is shown in 1Hz increments, dff refers to mean z-scored activity, se refers to standard error of that activity
File: figure2.xlsx
-fig2b_example1_ensure, fig2b_example2_ensure, fig2b_example3_ensure, fig2b_example4_ensure: z-scored activity of example VTA-DA cells during Ensure IG infusion (IG from x=600 to x= 1320). Time is shown in 1Hz increments, z refers to mean z-scored activity, se refers to standard error of that activity.
-fig2b_example1_water, fig2b_example2_water, fig2b_example3_water, fig2b_example4_water: z-scored activity of example VTA-DA cells during water IG infusion (IG from x=600 to x= 1320). Time is shown in 1Hz increments, z refers to mean z-scored activity, se refers to standard error of that activity.
-fig2c_data: z-scored activity of cross-registered neurons during IG infusion of Ensure and water
-fig2d_data: z-scored activity of cross-registered neurons after IG infusion of Ensure and water
-fig2e_example1_ig, fig2e_example2_ig, fig2e_example3_ig, fig2e_example4_ig: z-scored activity of example VTA-DA cells during water IG infusion (IG from x=600 to x= 1320). Time is shown in 1Hz increments, z refers to mean z-scored activity, se refers to standard error of that activity.
-fig2e_example1_ip, fig2e_example2_ip, fig2e_example3_ip, fig2e_example4_ip: z-scored activity of example VTA-DA cells during water IP injection (IP given at x=600). Time is shown in 1Hz increments, z refers to mean z-scored activity, se refers to standard error of that activity.
-fig2e_data: z-scored activity of cross-registered neurons after IG infusion of water and IP injection of water
-fig2f_example1_water, fig2f_example2_water, fig2f_example3_water, fig2f_example4_water: z-scored activity of example VTA-DA cells during water IP injection (IP given at x=600). Time is shown in 1Hz increments, z refers to mean z-scored activity, se refers to standard error of that activity.
-fig2f_example1_salt, fig2f_example2_salt, fig2f_example3_salt, fig2f_example4_salt: z-scored activity of example VTA-DA cells during 3M NaCl IP injection (IP given at x=600). Time is shown in 1Hz increments, z refers to mean z-scored activity, se refers to standard error of that activity.
-fig2f_data: z-scored activity of cross-registered neurons after IP injection of 3M NaCl and water
File: figure3.xlsx
-fig3b_injection_only: z-scored activity of VTA-DA neurons following saline or clozapine N-oxide (CNO) in mice expressing hM4Di in lateral hypothalamic GABAergic (LH-GABA) neurons
-fig3b_postig: z-scored activity of VTA-DA neurons following water IG infusion and injection of either saline or CNO in mice expressing hM4Di in LH-GABA neurons
-fig3c_ig: z-scored activity of VTA-DA neurons following water IG infusion in mice that were sated and injected with saline, dehydrated and injected with saline, or sated and injected with CNO in mice expressing hM3Dq in subfornical organ excitatory (SFO-CaMKII) neurons
-fig3c_ip: z-scored activity of VTA-DA neurons following water IP injection in mice that were sated and injected with saline, dehydrated and injected with saline, or sated and injected with CNO in mice expressing hM3Dq in SFO-CaMKII neurons
File: figure4.xlsx
-fig4b_ensure: GRAB-DA responses (expressed as dF/F) during ensure lick bouts, recorded by mouse in VTA, dorsal striatum (DS), basolateral amygdala (BLA), infra limbic prefrontal cortex (IL), nucleus acccumbens (NAc) medial shell (MSH), NAc core region (CORE), or NAc lateral region (LAT).
-fig4b_water: GRAB-DA responses (expressed as dF/F) during water lick bouts, recorded by mouse in VTA, DS, BLA, IL, MSH, CORE, or LAT
-fig4c_ensure: GRAB-DA responses (expressed as dF/F) during ensure IG infusion, recorded by mouse in VTA, DS, BLA, IL, MSH, CORE, or LAT
-fig4c_water: GRAB-DA responses (expressed as dF/F) during water IG infusion, recorded by mouse in VTA, DS, BLA, IL, MSH, CORE, or LAT
-fig4d_ensure: GRAB-DA responses (expressed as dF/F) after ensure IG infusion, recorded by mouse in VTA, DS, BLA, IL, MSH, CORE, or LAT
-fig4d_water: GRAB-DA responses (expressed as dF/F) after water IG infusion, recorded by mouse in VTA, DS, BLA, IL, MSH, CORE, or LAT
-fig4e_bla_trace: average z-scored activity trace BLA-projecting VTA-DA cells during water IG infusion (IG from 10 min to 16 min). Time is shown in 0.8Hz increments, z refers to mean z-scored activity, se refers to standard error of that activity
-fig4e_nac_trace: average z-scored activity trace NAc-projecting VTA-DA cells during water IG infusion (IG from 10 min to 16min). Time is shown in 0.8Hz increments, z refers to mean z-scored activity, se refers to standard error of that activity
-fig4e_barplot: z-scored activity of BLA-projecting and NAc-projecting VTA-DA neurons following water IG infusion
File: figure5.xlsx
-fig5b_data: flavor preference for flavors paired with water infusion vs. 600 mM NaCl infusion (expressed as %) before and after training in wild type mice
-fig5d_msh_dehy: GRAB-DA responses in NAc MSH (expressed as dF/F) during lick bouts of NaCl-paired flavor on first and final days of training
-fig5d_msh_hy: GRAB-DA responses in NAc MSH (expressed as dF/F) during lick bouts of water-paired flavor on first and final days of training
-fig5d_bla_dehy: GRAB-DA responses in BLA (expressed as dF/F) during lick bouts of NaCl-paired flavor on first and final days of training
-fig5d_bla_hy: GRAB-DA responses in BLA (expressed as dF/F) during lick bouts of water-paired flavor on first and final days of training
-fig5e_mcherry: flavor preference for flavors paired with water infusion vs. 600 mM NaCl infusion (expressed as %) before and after training in mice in which VTA-DA neurons were not inhibited using GtACR (mCherry controls)
-fig5e_gtacr: flavor preference for flavors paired with water infusion vs. 600 mM NaCl infusion (expressed as %) before and after training in mice in which VTA-DA neurons were inhibited using GtACR
Code/software
MATLAB (v2020b) was used to analyze the data in the original manuscript. Statistical tests on this dataset can be equally as well performed using Prism, R, or any other major data processing software/code.
Access information
The data was collected in a research laboratory (Knight Lab at UCSF): https://knightlab.ucsf.edu/.
The graphical displays of this source data can be found at https://www.nature.com/articles/s41586-022-04954-0
