Journal Club

Highlighting recently published papers selected by Academy members

The hippocampus has brief but critical role in early task learning

Inactivating hippocampal neurons, shown here in red, briefly impaired rats’ ability to learn to press a lever to earn a reward. The discovery suggests that the hippocampus may play a key role in the initial memory formation necessary to learn to perform a task. Image credit: Bernard Balleine

Inactivating hippocampal neurons, shown here in red, briefly impaired rats’ ability to learn to press a lever to earn a reward. The discovery suggests that the hippocampus may play a key role in the initial memory formation necessary to learn to perform a task. Image credit: Bernard Balleine

How the brain learns new tasks is among the biggest and oldest questions in neuroscience. A recent study in Nature Neuroscience offers a new, potentially key part of the answer: the dorsal hippocampus is involved in the earliest stages of the learning necessary to perform tasks, but is not required later in the process. Working in rats, researchers demonstrated that the animals needed their hippocampus to associate an action with a reward one day after initial training. But seven days later, they didn’t use that part of the brain to carry out the same task.

The discovery seems to resolve a 20-year-long debate about whether the hippocampus is required to learn a new task. Some past experiments, particularly in primates, suggested it was necessary. Others, in rats, suggested it wasn’t, notes coauthor Laura Bradfield, a behavioral neuroscientist at the University of Technology Sydney in Australia. Another body of literature, investigating learning related to fear, had found the hippocampus to be involved only in the earliest stages of memory formation. Bradfield suspected the dorsal hippocampus might have a similarly brief involvement in learning, and that past rodent studies had just missed the time window.

To test her suspicion, she trained groups of rats to press two levers in a chamber. Some groups of rats had a functional hippocampus, while other groups had theirs disabled via a chemogenetics approach using chemically engineered molecules. Researchers wanted the rats to learn that the left lever always delivered grain pellets, and the right lever always delivered sugar solution. Then, the following day, Bradfield let the rats loose in a cage of grain pellets to eat their fill. In principle, they’d then be sick of grain and prefer sugar. Next, she put the rats back in the chamber with the two levers. Although neither lever delivered a reward this time, rats with an intact hippocampus still preferentially pressed the right lever for sugar, indicating they’d previously learned to associate it with a specific reward. Rats with an inactivated hippocampus pressed both levers equally, suggesting they didn’t remember which lever delivered what food reward.

To counterbalance the experiment, researchers had some groups of rats learn the left lever was for sugar, and the right for grain, and had the rats fill up on sugar solution instead of pellets. The rats still exhibited the same behavioral trends, becoming satiated on the abundant reward. When their hippocampus was intact, they preferentially pressed the lever for the rarer, valued reward.

But strangely, a week later, all of the rats selectively pressed the lever for the valued reward, regardless of whether their hippocampus was intact at any point during training or testing. “It’s quite surprising because you’d think if you need it during training, then you need it,” Bradfield says. Even though the rats had been in their cages all week, without experiencing other stimuli that might change their behavior, their brains had changed over the course of seven days, somehow allowing them to compensate for an inactive hippocampus. It’s not clear why. But Bradfield speculates that the hippocampus was critical for the initial formation of an episodic, autobiographical memory necessary to perform the task. Then, over time, other brain structures involved in learning consolidated enough information from that one training to compensate for the missing hippocampus.

Rats trained to associate levers with rewards showed different behavioral responses, depending on whether they had a functional dorsal hippocampus. Image credit: Bernard Balleine

Rats trained to associate levers with rewards showed different behavioral responses, depending on whether they had a functional dorsal hippocampus. Image credit: Bernard Balleine

The finding is a “nice reconciliation” of the literature, in which researchers have debated the role of the hippocampus in making decisions that take the value of goals into account, says David Redish, a neuroscientist at the University of Minnesota, Twin Cities, who was not involved in the recent work. The paper’s findings suggest it is necessary for early learning, he adds, consistent with the role of the hippocampus in other tasks, such as schema-building or memory formation. Researchers in the field, Redish notes, hadn’t considered that the hippocampus might be only transiently involved in learning these goal-directed decisions. “I don’t know why nobody thought of it, but nobody was looking across time,” he says.

Future studies can now begin to build on the discovery to more precisely investigate the hippocampus’ role in decision-making, adds postdoctoral neuroscientist Oliver Vikbladh at the Institute for Cognitive Neuroscience of University College, London. Eventually, there could be implications for disease treatments. Millions of people suffer from diseases such as Alzheimer’s that damage the hippocampus. “That’s understood as a memory disorder,” Vikbladh notes. Recent work, including this study, suggests that the hippocampus has a broader role in human behavior, affecting, says Vikbladh, “the strategies you need to make decisions.” In hopes of probing possible therapeutic applications, Bradfield says she’s already developing a preclinical model of decision-making in Alzheimer’s mice, looking to see if they also exhibit this transient deficit in decision-making.

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