Thirst Controls Motivated Behavior by Modulating Neural Activity in Mice
Post by Lincoln Tracy
What's the science?
Motivation refers to an internal psychological state that explains how we can respond to the same stimulus or event in different ways depending on the context and our needs. For example, if you see a glass of water on a table, you are more likely to want to drink it after you have been exercising and are thirsty compared to when you had a glass of water ten minutes earlier. Traditionally, scientists have thought that motivational states control our behavior by altering the salience of a stimulus—that is, how noticeable or important we perceive something in our environment to be—depending on how much reward or pleasure we would get from the stimulus. Keeping in line with our example, we are more likely to notice the water when we are thirsty as drinking it then would be more rewarding. This week in Science, Allen and colleagues set out to uncover the neural mechanisms and activity that control these motivational states in the context of thirst.
How did they do it?
The authors first performed surgery on mice, so they could later use electrodes to record their brain activity. After the mice had recovered from the surgery they were deprived of water and trained in a modified version of a Go/No-Go task. In each trial of this task, mice were presented with one of two odors—ethyl acetate (the Go cue; a sweet-smelling liquid used in nail polish removers) or 2-pentatone (the No-Go cue; a colorless liquid found in apples). When ethyl acetate was presented in the trial, mice could lick a water spout and receive water as a reward. There was no reward associated with the 2-pentatone cue, meaning that the mice had no motivation to lick the water spout in these trials. The mice went through hundreds of trials of the task, learning to lick the water spout when they smelled ethyl acetate until eventually they had had enough to drink and stopped responding to the cue. Once the mice stopped drinking, another several dozen trials were undertaken where the mouse was presented with the same cues but did not drink because they were sated (i.e. satisfied). The authors used electrodes implanted throughout the brain to record brain activity while the mice completed the task to examine how neural activity changed throughout the brain at different stages of each trial, and throughout the whole task. Finally, the authors used optogenetics, a technique in which neural activity can be controlled by shining light on neurons that have been genetically modified to respond to light, to activate thirst neurons in the hypothalamus.
What did they find?
The authors found that neurons in different brain regions were active at different times during individual trials and throughout the task overall. Neurons could be grouped into one of three different clusters: state-related clusters that were active depending on whether the mouse was thirsty or not; cue-related clusters that were active or suppressed during the presentation of the odors; and behavior-related clusters that were only active in thirsty mice during Go trials when they drank the water. Each brain region where activity was recorded contained neurons belonging to each cluster, but specific regions had more of one type of neuron compared to other regions. In thirsty mice the presentation of the Go cue produced a rapid increase in neural activity, yet the same Go cue and the No-Go cue did not elicit the same activity increase in sated mice. These results suggest that the motivation to drink prior to the onset of drinking behavior is not driven by a broad change to all cue-responsive neurons, but rather a specific subset of neurons. When the authors optogenetically activated thirst neurons in the hypothalamus after mice were sated, they found that brain activity was temporarily restored to that of the ‘thirsty state’.
What's the impact?
This study found that being thirsty places the brain in a particular motivational state. When we realize that water is available nearby—such as seeing a glass of water—there is a surge of activity in our brain that changes our motivation, resulting in us picking up the glass and drinking the water. Once we drink the water and are no longer thirsty, our brain state changes to prevent the same stimulus (a glass of water) from eliciting the same reaction (drinking the water). Further research is needed to determine whether these findings represent a more general form of arousal and motivational behavior in different states beyond thirst.
Allen et al. Thirst regulates motivated behavior through modulation of brainwide neural population dynamics. Science (2019). Access the original scientific publication here.