The Hippocampus Can Predict Whether an Action Will Lead to a Reward

Post by Trisha Vaidyanathan

The takeaway

The ventral hippocampus (vHPC), via its projections to the medial prefrontal cortex, is important for encoding the context of a reward. This pathway is required to update the causal relationship between an action and a reward and adjust behavior accordingly. 

What's the science?

It has long been debated whether the hippocampus plays a role in “goal-directed actions”, something we do every day. For example, you may put money in a nearby vending machine (an action) so you can eat a candy bar (a goal). Choosing to take this action is dependent on your understanding that there is a causal relationship between putting money in a vending machine and getting a candy bar, also known as an “action-outcome contingency”. However, if candy bars randomly drop from the vending machine without your money, you may stop believing in the “action-outcome contingency” and stop putting money in the vending machine. Critically, you will only update the “action-outcome contingency” in the context of the vending machine and will likely still choose to use money at a store, or maybe even another vending machine. This week in Current Biology, Piquet and colleagues demonstrate that the ventral hippocampus (vHPC) is critical for context-specific learning that shapes behaviors in response to changing action-outcome contingencies.

How did they do it?

The authors used a behavioral test for rats to model action-outcome contingency. Rats were trained on two different action-outcome contingencies: pushing lever 1 resulted in a grain pellet, and pushing lever 2 resulted in a sugar pellet. Next, one of those action-outcome contingencies was “devalued” by giving rats access to the pellets without needing to push the lever. Finally, they tested the rats by presenting them with both levers – typically, rats are less likely to choose the lever associated with the “devalued” pellet, or the pellet they were given free access to. To test the role of the vHPC, the authors trained rats on the task after creating a lesion in the vHPC or using chemogenetics to selectively silence the vHPC neurons during specific phases of the task.

Next, the authors investigated the role of context in action-outcome contingency. Rats went through extensive pre-exposure to the behavior chamber, which is known to reduce its effectiveness as a context cue through a concept called “latent inhibition” and examined how this altered their response to the action-outcome contingency change. The authors also trained rats with or without vHPC silencing on a Pavlovian context conditioning test, in which they were trained to associate two different behavioral chambers (contexts) with two different rewards, then the authors devalued one of the rewards and tested the ability of rats to differentiate between the two chambers.

Lastly, the authors investigated whether these vHPC functions are mediated by vHPC projections to the medial prefrontal cortex by using chemogenetics to specifically silence the vHPC terminals in the medial prefrontal cortex during the action-outcome contingency task.

What did they find?

First, the authors demonstrated that rats with vHPC lesions are insensitive to changes in an action-outcome contingency. After the rats were given full access to one of the pellets, the rats with lesions failed to preferentially choose the other pellet in the “test phase”. Similar results were found when the authors chemogenetically silenced vHPC neurons during the training, but not the test phase. Together, this demonstrated that vHPC is necessary to acquire new causal information.

Next, the authors lessened the effectiveness of the behavior chamber as a context cue through pre-exposure, or “latent inhibition”, and found this caused the rats to be less sensitive to the action-outcome contingency change. This demonstrated that encoding the context of a reward is necessary to respond to an action-outcome contingency change. The authors then demonstrated that vHPC is specifically important for encoding the context of the reward. Rats with vHPC lesions or chemogenetic silencing were unable to differentiate between a “devalued” context and a “valued” context in the Pavlovian context conditioning assay.

Lastly, the authors confirmed that the vHPC exerts its effect on goal-directed actions via its projections to the medial prefrontal cortex, by demonstrating that specifically silencing the vHPC terminals in the medial prefrontal cortex had the same negative effect on behavior as the vHPC silencing.

What's the impact?

This study identifies a critical role of the vHPC-to-cortex circuit in goal-directed actions by demonstrating that the circuit is necessary to encode the context of a reward, update the causal link between action and outcome, and adapt behavior appropriately. These findings are critical to our understanding of fundamental, everyday behavior. 

Access the original scientific publication here.

Brain Volume in the Hippocampus is Influenced by Genetics

Post by Lani Cupo

The takeaway

Gray matter volume along the length of the hippocampus is influenced by genetic factors, which can be identified in living humans.

What's the science?

The volume of the hippocampus is considered to be about 80% “heritable”, meaning 80% of the variability of hippocampal volume is attributable to genetic variation. Measuring the volume of the entire hippocampus, however, neglects to consider that some regions of the hippocampus may be more susceptible to environmental influences than others. Examining the heritability of subfields, or regions within the hippocampus, may provide better estimates of whether the heritability of volume differs between regions. This week in NeuroImage, Pine and colleagues investigated the heritability of hippocampal subfields using magnetic resonance imaging (MRI) data, finding volume is influenced both by genetic factors general to the entire hippocampus, and specific to individual subfields. 

How did they do it? 

The authors used MRI from both children and adult twin pairs from three different datasets, including both dizygotic and monozygotic twins. They built biometric models to compare how highly correlated volumes were between monozygotic (single egg) and dizygotic (two eggs) twins. This method allowed them to detect differences in hippocampal subfield volume that could be attributed to sources of variance that are either genetic or environmental. For example, if there is variance in the hippocampal volumes of monozygotic twins (who begin life genetically identical) it can be attributed to an individual environmental influence (e.g. different levels of education). By examining how correlated hippocampal volumes were between monozygotic twins, compared to how shared hippocampal volumes were between dizygotic twins, the authors could estimate how much of the volume was heritable versus due to environmental influences. They compared the performance of different models to assess which one best fit their data before interpreting results. The hippocampal subfields examined were the head, body, and tail, dividing the hippocampus along its longitudinal axis (if you imagine the hippocampus as a c-shape uncurled). By including both males and females and both children and adults in this study, the authors were able to investigate how heritability by subfield differs across sexes and ages. 

What did they find?

The authors didn’t find any differences in the heritability of volume across the different subfields. This suggests there isn’t a particular subfield where volume is more heritable than others, however, it is possible that using another division of the hippocampus or treating it as a gradient, rather than distinct regions, may reveal other subtle differences. 

Nevertheless, the authors did find evidence for subregion-specific genetic components, meaning different genes might contribute to the volume of different subfields. Subfield-specific genetic contribution was found to be both sex and age-dependent. In both sexes and in both children and adults, subfield-specific genetic contributions were found for the tail of the hippocampus. In contrast, subfield-specific genetic contributions were found for the head only in children (both sexes). Finally, subfield-specific contributions were found for male children only for the body of the hippocampus. The authors reported that these sex and age differences do not follow known systematic patterns, however, it is of interest that the genetic influence on hippocampal subfield volume is not constant across ages, and other properties of the hippocampus, such as white matter, may better reflect age-related changes. 

What's the impact?

These findings suggest the head, body, and tail may not show differences in heritability of gray matter volume, however, they show subfield-specific genetic contributions that differ across subfields by age and sex. The authors also demonstrate that noninvasive imaging can be used in living humans to estimate genetically based individual differences, which can set the stage for future population studies. 

Access the original scientific publication here

The Role of Dopamine in Integrating Costs, Benefits and Motivation

Post by Soumilee Chaudhuri

The takeaway

Eshel and colleagues found that dopamine release in the striatum is related to both the costs and benefits of a decision and that higher motivational states are associated with lower dopamine release. 

What's the science?

Dopamine (DA) release in two distinct regions of the brain: ventral and dorsal striatum, has been associated with the motivation underlying decision making. But there is insufficient evidence as to whether DA released from these regions impact cost, benefit and how this might be influenced by motivation. An article published in Neuron this week investigated the role of dopamine in cost, benefit and motivation  using mouse models and optogenetics to understand 1) how dopamine responds to variation in the cost and benefit of an action and 2) how these changes in dopamine release are associated with the animal’s motivation to act.

How did they do it?

The researchers measured motivation in mice to obtain a natural reward (sucrose) or an artificial reward (optogenetic stimulation of DA in the brain) while recording DA release in the ventral and dorsal striatum. This helped them study how DA dynamics are involved in reward and behavior. First, mice were trained to poke their nose to get a sweet reward (sucrose); thereafter, the number of pokes to get the same reward was increased every 10 minutes, which the authors considered to be the “cost” associated with the reward. The concentration and amount of sucrose quantity were constant within a session but varied with different sessions. The mice were analyzed based on their sensitivity to changes in reward and cost. In a separate group of mice, the researchers used optogenetics to directly stimulate the dopamine neurons in the brain and record & analyze its release; this was done to see the impact of dopamine release on motivation, as the mice were taught to poke for the optogenetic stimulation accompanied by light and sound cues.

What did they find?

The researchers found that dopamine activity reflected both the size of the reward (i.e., benefit) as well as the effort that has already been made to achieve the reward (i.e., the cost). This was a key takeaway as it emphasized that DA was not preferentially associated with either benefit or cost associated with a task. The researchers also observed an unexpected and counterintuitive link between DA release and motivation: they found that highly motivated mice had lower dopamine release for a fixed reward and vice-versa. The authors speculate that this finding could be similar to what is observed in the cases of drug users, where high motivation is associated with low drug-induced dopamine release. Additionally, it was also found that optogenetics-induced DA stimulation was influenced by the environment, costs, rewards, as well as motivation. 

What's the impact?

This study shows that dopamine released in the brain’s striatum reflects the cost and benefit of a task, as well as the motivation underlying that task. Dopamine dynamics for each reward represents the size of the reward as well as the cost that’s already been paid for the task. The study also shows that dopamine release goes down in high-motivation states. Overall, the findings of this study are crucial to understanding the intricacies of the role of dopamine as a neuromodulator in the brain.