DOI: 10.5061/dryad.zgmsbccsf
title: Data from: Dopamine subsystems that track internal states

description: 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.
description: # Data from: Dopamine subsystems that track internal states Dataset DOI:
 [10.5061/dryad.zgmsbccsf](https://doi.org/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](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](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/](https://knightlab.ucsf.edu/). The graphical
 displays of this source data can be found
 at [https://www.nature.com/articles/s41586-022-04954-0](https://www.nature.com/articles/s41586-022-04954-0)