Research Article

Thirst regulates motivated behavior through modulation of brainwide neural population dynamics

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Science  19 Apr 2019:
Vol. 364, Issue 6437, eaav3932
DOI: 10.1126/science.aav3932

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Neuron activity across the brain

How is it that groups of neurons dispersed through the brain interact to generate complex behaviors? Three papers in this issue present brain-scale studies of neuronal activity and dynamics (see the Perspective by Huk and Hart). Allen et al. found that in thirsty mice, there is widespread neural activity related to stimuli that elicit licking and drinking. Individual neurons encoded task-specific responses, but every brain area contained neurons with different types of response. Optogenetic stimulation of thirst-sensing neurons in one area of the brain reinstated drinking and neuronal activity across the brain that previously signaled thirst. Gründemann et al. investigated the activity of mouse basal amygdala neurons in relation to behavior during different tasks. Two ensembles of neurons showed orthogonal activity during exploratory and nonexploratory behaviors, possibly reflecting different levels of anxiety experienced in these areas. Stringer et al. analyzed spontaneous neuronal firing, finding that neurons in the primary visual cortex encoded both visual information and motor activity related to facial movements. The variability of neuronal responses to visual stimuli in the primary visual area is mainly related to arousal and reflects the encoding of latent behavioral states.

Science, this issue p. eaav3932, p. eaav8736, p. eaav7893; see also p. 236

Structured Abstract


Motivational drives are internal states that can explain why animals adaptively display distinct behaviors in response to the same external stimulus. Physiological needs (e.g., for food and water) are thought to produce specific drives that engage particular goal-directed behaviors to promote survival. These drives are established through the activity of populations of hypothalamic neurons that sense physiological variables and relay this information to other parts of the brain. However, it is unclear how the activity of these hypothalamic neurons activates and coordinates other brain systems involved in sensation, decision-making, and action in order to produce the appropriate goal-directed behavior. The cellular dynamics of brainwide states underlying basic survival drives have heretofore remained inaccessible.


Understanding the neural basis of motivated behavior would require measuring activity within distributed neural circuits in the brain and studying how this activity is regulated by the animal’s motivational state. Recent advances in extracellular electrophysiological recording technology have enabled large-scale measurements of neuronal activity throughout the brains of behaving animals. This technology could lead to a spatiotemporal map of activity flow across the brain as an animal senses and responds to stimuli under different conditions. By examining the animal in different motivational states, we could determine how these states are represented in diverse brain regions and how these states influence neuronal activity across the brain to alter behavior.


We recorded the activity of ~24,000 neurons throughout 34 brain regions during thirst-motivated choice behavior; these recordings were performed across 87 sessions from 21 mice as they gradually consumed water and became sated. We found that more than half of recorded neurons were modulated by this task, with a rapid and widespread response to a water-predicting olfactory cue preceding sustained activity related to water acquisition. The animal’s satiety state gated this wave of activity: In satiated mice, the same sensory cue produced only a transient change in activity and no behavioral response. Surprisingly, the spontaneous baseline activity of neurons across many brain regions was also modulated by the animal’s satiety state.

We found diverse correlates of the task at the single-neuron level, with many neurons’ activity correlating with specific sensory cues or behavior, and some of them highly modulated by satiety state. Neurons from each of these groups were distributed throughout the brain, with each brain area differing in the relative proportions of different types of neurons. We separated the high-dimensional population activity dynamics into lower-dimensional state-, cue-, and behavior-related modes. Whereas the cue- and behavior-related modes were primarily modulated by the task in a satiety state–dependent manner, activity along the state mode was persistent throughout the trial, including the period before odor onset. Thus, there existed a brainwide representation of satiety state that appeared to gate the flow of activity in response to sensory inputs.

Finally, as a causal test of the role of this widespread encoding of satiety state, we optogenetically stimulated hypothalamic thirst neurons and caused mice to perform more trials after reaching satiety. We found that this focal stimulation returned the behavior, brainwide single-neuron within-trial dynamics, and brainwide single-neuron correlates of satiety state back to the state corresponding to thirst. Stimulation also specifically modulated activity along the satiety-related mode in a subset of brain areas.


Our experiments revealed a global representation of the thirst motivational state throughout the brain, which appears to gate the brainwide propagation of sensory information and its subsequent transformation into behavioral output.

Brainwide dynamics of thirst motivational drive.

Top left: Potential models for widespread or selective regulation of neural dynamics by thirst. Bottom left: Tracks of Neuropixels electrodes used to record activity from different brain regions during thirst-motivated behavior. Center: Brainwide activity dynamics of individual neurons in response to a sensory cue while a mouse was thirsty and sated. Top right: Neural activity correlated with satiety state. Bottom right: Low-dimensional dynamics of task-related activity.


Physiological needs produce motivational drives, such as thirst and hunger, that regulate behaviors essential to survival. Hypothalamic neurons sense these needs and must coordinate relevant brainwide neuronal activity to produce the appropriate behavior. We studied dynamics from ~24,000 neurons in 34 brain regions during thirst-motivated choice behavior in 21 mice as they consumed water and became sated. Water-predicting sensory cues elicited activity that rapidly spread throughout the brain of thirsty animals. These dynamics were gated by a brainwide mode of population activity that encoded motivational state. After satiation, focal optogenetic activation of hypothalamic thirst-sensing neurons returned global activity to the pre-satiation state. Thus, motivational states specify initial conditions that determine how a brainwide dynamical system transforms sensory input into behavioral output.

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