Life can be difficult. We have so many decisions to make. It’s a good thing we have an orbitofrontal cortex and hippocampus to help us. According to researchers at UC Santa Barbara, these brain areas work together to help us sort through tasks that require resolving ambiguity, that is, situations in which the meaning of stimuli changes depending on the context.


“I would say this is the basis of cognition,” says UCSB neuroscientist Ron Keiflinwhose lab investigates the neural circuits behind valuation and decision-making. “This ensures that we do not behave like simple robots, which always respond in the same way to every stimulus. Our ability to understand that the meaning of certain stimuli is context dependent gives us flexibility; it is what allows us to act in a situationally appropriate manner.”


For example, he said, your phone may ring, but whether you answer depends on several factors, including where you are, what you’re doing, what time it is, who’s calling and other details. It’s a single stimulus, Keiflin said, “but depending on the background conditions, it will be processed differently and you might decide to deal with it in a different way.”


The research, published in the magazine Current Biologyis the first to causally test the relative contributions of the orbitofrontal cortex and hippocampus in this contextual disambiguation process.


Making meaning


The orbitofrontal (OFC) occupies the front part of the brain, just above the eyes. It is associated with reward valuation, planning, decision-making and learning. The dorsal hippocampus (DH) is located further back, deeper in the brain, and is associated with spatial navigation and episodic memory.


“Historically, research on the orbitofrontal cortex and hippocampus has largely proceeded in parallel, but ultimately these different lines of research came to very similar conclusions for these two brain regions,” Keiflin said.


“The idea is that these two brain areas encode a ‘cognitive map’ of the structure of the world,” he said, noting that it doesn’t have to be a purely spatial map. “It is a map of the causal structure of the environment; you can use this card to mentally simulate the consequences of your actions and choose the best path forward.


This cognitive map is exactly what you need to understand that the meaning of a signal depends on the context. But previous studies had not explicitly tested the role of these regions in context disambiguation.


To understand how these two regions contributed to contextual disambiguation, the researchers devised an experiment in which rats were exposed to brief auditory cues presented in a bright or a dark context (the context was changed by turning a light bulb on or off). The auditory signals sometimes led to a reward (a small amount of sugar water), but not always; other times the same cues would have no consequences, making them ambiguous predictors of rewards. Ultimately, the rats would learn that one auditory cue was rewarded only in the light, but not in the dark, context; while the opposite was true for the other auditory signal. In other words, they would learn that the meaning of the signals was context dependent.


The researchers knew when the rat had learned to distinguish between the two situations when the rats approached and licked the sugar water cup in anticipation of the reward in one environment, or not in the other environment.


To determine how the orbitofrontal cortex and hippocampus were involved in this contextual disambiguation process, the researchers used “chemogenetics” – a tool that allowed them to temporarily inactivate one of these structures during the task.



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