RESEARCH

How do we make behavioral decisions? Imagine you are driving up to an intersection: You look at the incoming traffic, hear cars coming up behind you while also checking for street signs or a traffic light. All this sensory information has to be rapidly integrated with your prior experiences and internal motivations into a single behavioral decision. Do you take the turn or not?

The transformation of complex sensory information into behavioral decisions requires the coordinated activity of many brain regions. We want to understand how these regions process sensory inputs and interact with each other to generate a unified behavioral decision. We therefore study the brain activity of awake mice while they perform a well-controlled behavioral task. This allows us to precisely control the available sensory inputs and then closely watch the activity in the brain as it transforms sensory information into behavior. In many of our experiments we focus on regions in the cortex (the outer shell of the brain) but we also study deeper brain structures, such as the striatum and the superior colliculus.

Activity of individual neurons in the cortex while a mouse is forming a behavioral decision. Will it respond left or right?

A particular focus of the lab is on how decisions are affected by brain states. Imagine you are back at the intersection. There is suddenly loud honking and people are gesturing behind you. Your heart beats faster, you have to make a quick decision. However, the street signs seem suddenly harder to read and you can’t remember if this was the right place to make a turn. Why is it, that sometimes our brain seems to work less well when we need it the most? Anyone who ever had a blackout during an exam might wonder the same thing. To answer this question, we are studying how neuromodulators, such as acetylcholine or noradrenaline, change the function of neural circuits and how this affects sensory processing and decision-making.

Sensory-guided decision making
Generating sensory-guided decisions involves the coordinated interaction of many brain areas. We therefore use widefield imaging and 2-photon microscopy to monitor the cortex-wide activity of mice that are performing a multisensory decision-making task.

Combining electrophysiology, optogenetic stimulation and cortical imaging to study brain-wide activity

To simultaneously capture the activity of deep brain areas, we combine functional imaging with high-density electrophysiology to capture the activity of thousands of neurons across the brain. This gives us a unique view into the activity of brain-wide neural networks and how they give rise sensory perception and behavior.

Neuromodulation of cortical circuits and behavior
Behavioral decisions and their underlying neural dynamics vary widely across different behavioral states. Whether we are focused on a challenging task or thinking about past experiences determines how we interpret and respond to external stimuli. The basal forebrain (BF) is a major driver of such state-dependent fluctuations and releases the neuromodulator acetylcholine throughout the brain. We want to understand the function of different nuclei in the BF and how they affect cortical areas to enhance sensory perception. To achieve this goal, we simultaneously record the activity of different BF nuclei and cortical circuits and also use optogenetic manipulation to selectively change the activity of cholinergic projection neurons.neuropixels

Better understanding BF function could also be important for clinical applications since degradation of cholinergic circuits leads to a significant loss of cognitive functions in many neurodegenerative disorders, such as Alzheimer’s or Schizophrenia.

Pathway-specific information transfer
Different brain areas are heavily interconnected and constantly send information back and forth to create the brain-wide neural dynamics that give rise to behavior. What information is transmitted is hereby often custom-tailored to the recipient. For example, a cortical area will send different information to another cortical area compared to what is sent to deeper brain areas, such as the basal ganglia or the brainstem. The neurons that form connections between brain areas are therefore functionally distinct ‘output channels’ that are crucial for the communication within large-scale neural networks.

We want to study the function of specific projection neurons in the cortex to reveal what information they sent to other brain areas and how distinct cortical projection pathways shape sensory perception and behavior. By combining pathway-specific imaging with BF recordings, we also study how cortical information transfer is affected by neuromodulation.

Using viral labeling techniques, we can mark specific projection pathways throughout the brain (left). Projection neurons can be labeled with different colors to study their respective function simultaneously with other neurons (right).

Flexible neural interfaces
Our research aims to generate new insights on the function of neural circuits that can ultimately lead to new treatments of neurological disorders, such as the targeted stimulation of different BF nuclei in humans. A prominent problem for neuroelectronic stimulation or recording devices in humans is the degradation of signal quality due to scar tissue formation. Consequently, effective treatments, such as deep brain stimulation, often loose their efficacy over time.

The Department for Neuroelectronics develops different types of flexible electrode arrays. By playing an active role in the development and testing of these devices we obtain novel tools for the chronic study of brain function that may ultimately be employed in humans.

In collaboration with other groups at the Department for Neuroelectronics we are involved in the development and testing of new, flexible electrophysiological recording arrays. These devices can record and stimulate neural activity over long time-scales, making them ideally suited to study long-term changes in neural activity, and a potential therapeutic tool in humans. Moreover, flexible electrode arrays could serve as a platform for novel neuropharmacological sensors to measure the concentration of different neuromodulators in the brain.