Aim

To better understand how sensory information is encoded in the brain and how it is modulated by learning and by an animal’s internal states.

Background

The habenula is an evolutionary conserved brain region that has caught the attention of neuroscientists in recent years, due to its strong link to depression, addiction, sleep and social interactions. It receives multiple inputs from different brain regions, which provide information about an animal’s sensory world and internal state, such as reward expectation.  

Additionally, the habenula regulates key neurotransmitters, such as serotonin, dopamine and acetylcholine – all of which play critical roles in learning, memory, motivation and mood. Interested in the connection between sensory processing and higher-level functions such as experience-dependent learning and memory, the Yaksi lab has been investigating the relationship between the habenula and other brain regions such as the hippocampus and the amygdala, which have known roles in mood regulation, learning and memory.

Key Research Questions

• What drives ongoing activity in the brain and how does this ongoing activity relate to internal states and experience-dependent learning in brain regions known to be important for emotional processing and learning?

• How do changes in ongoing brain activity modify sensory computations in these brain regions?

Tools & Methods

The Yaksi group uses two-photon microscopy, electrophysiology, genetic and applied mathematical tools  to measure and analyze neural activity across the whole brain of awake, behaving juvenile zebrafish in naturalistic and virtual reality environments.

Research

Previous work from the Yaksi group showed that the habenula integrates olfactory and visual information.

The team further demonstrated that depriving the zebrafish of this multisensory input altered the corresponding multisensory representations in the habenula establishing the important link between incoming information from the outside world to its corresponding representation inside the brain.

In parallel, a separate study from the group showed that the habenula integrates multisensory information with internally generated brain activity – that is to say, signals that are generated from inside the brain itself.

Wanting to build upon these results, the team has been investigating where inside the brain these signals are coming from and what role these signals play, in experience-dependent learning, different behavioral states of the animal, and sensory information processing.

After extensive analysis of brain activity, the team discovered that numerous distinct brain regions (hippocampus, amygdala, hypothalamus) are the main driver of habenular activity.

“Our unpublished findings suggest that cortico-limbic brain regions and the habenula cooperate with each other and that the coherent interactions of this distributed brain-wide network are the main source of ongoing brain activity,” says Yaksi.

Finally, because the habenula controls the release of key neurotransmitters involved in learning, memory and mood, Yaksi hypothesizes that these brain interactions “are essential for regulating experience dependent changes in sensory computations and animals’ emotional states.”

To test this, the group has recently optimized methods which can record neural activity from multiple brain regions, simultaneously. By recording this neural activity from the brains of juvenile zebrafish while they are behaving and exploring in a virtual reality environment, the team will learn how experience-dependent learning and emotional states (internally represented in the brain) can affect neural connectivity and sensory information processing.

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Yaksi lab