A backstage entrance into the world of neuroscience and academia.

Flexi-Brains in uncertain times

“We have our strategy in place. A behavior has occurred one that is reprehensible, or wonderful, or floating ambiguously in between. What occurred in the prior second that triggered the behavior? This is the province of the nervous system. What occurred in the prior seconds to minutes that triggered the nervous system to produce that behavior? This is the world of sensory stimuli, much of it sensed unconsciously.”

­­­­­­­­­­­­­Robert Sapolsky [1]

Could you imagine our planet with its living organisms unable to make decisions? Rather impossible. From the simple “fight or flight” dilemma in animal kingdom till the most complicated societal issues, decisions are the guiding force in how the world evolves. As human beings, the decisions we make are made by us alone and add to our personality. However, we are not alone in this world. Our decisions are strongly dependent on our environment and on others’ choices. In this complex world of choices, we develop strategies or even habits, which help us to shape our life and future. But how vulnerable those strategies are? Are we able to easily adapt and re-learn new behavioral options? Indeed, there are situations in which even the most successful strategies and strongest habits do not lead to the expected outcomes. A well-suited example is the Pandemic – a societal shock – and our ability to adapt to this situation, which now became the “new normal” of our social action, to minimize the risk of becoming ill. Such alterations of learned behaviors or habits require mental effort and create changes in our brain and neuronal networks.

To understand more about the neuronal adaptations leading to a decision or a behavior, we need to take a step back; we need to focus on the sensory stimuli and systems prior to the outcome.

To understand more about the neuronal adaptations leading to a decision or a behavior, we would need to take a step back; we need to focus on the sensory stimuli and systems prior to outcome.  One well-developed model system is the auditory system of rodents, which use their acoustic environment as leading stimulus to adapt to an ever-changing world. By using modern systems neuroscience and recent technologies we are able to investigate the mechanisms underlying complex brain circuits and their role in the process of flexible decision-making. For example, the primary auditory cortex (A1) consists from six layers (supragranular I-III, granular IV, and infragranular Vb-Va-VI) with input, output and integration characteristics. The A1 is an essential node in the integrative brain network that encodes the behavioral relevance of acoustic stimuli, predictions, auditory-guided decision-making, and motor planning. However, its realization with respect to the cortical microcircuitry is poorly understood.

During my PhD years I spent hours, days, and years trying to get a deeper knowledge on that topic. I was (and I am still) fascinated with the concept uncertainty and cognitive flexibility! Therefore, I used chronic recordings of neuronal mass activity from thousands of neurons in parallel to better understand their cooperative action from this part of the brain of awake, freely behaving Mongolian gerbils in order to characterize layer-specific, spatiotemporal synaptic population activity. To mimic the scenario of learning the “new normal” I created a cognitively demanding paradigm where the animals had to interpret acoustic signals and decide to cross a hurdle, but the task rules changed many times. I trained the animals to first detect and subsequently to discriminate two pure tone frequencies in consecutive training phases. I measured the mesoscopic neuronal activity code distributed across cortical layers during the task and could demonstrate that not only sensory but also task- and choice-related information is represented in these neuronal patterns.

Based on modern statistical modeling approaches, I found infragranular layers (the deeper part) to be involved in auditory-guided action initiation during the detection of the tones. Supragranular layers (the upper part), particularly, are involved in the coding of choice options during tone discrimination. Most interestingly, I could show that the overall columnar synaptic network activity represents the accuracy of the opted choice. Moreover, cognitive flexibility challenged during multiple reversals of choice-outcome contingency in the task, was also represented in the firing patterns of neurons in the primary auditory cortex. During those cognitive processes, the infragranular layer VI (the deepest part) continuously updates the neural network in order to optimize the animals’ discrimination performance, while the supragranular layers promote choice accuracy, especially at states with higher task engagement and better performance [2].

Coping with our increasingly complex world with all its ambiguities requires cognitive resources.

We-neuroscientists we need to revisit the traditional idea of a sequential increase of processing complexity from early sensory processing towards motor preparation directly preceding a decision, which usually is described as the most valid model of how our brain works. In contrast, neuronal populations, even at the level of early sensory brain areas, integrate many variables that are important to command a decision, namely information about the expectation of a decision, of planned motor actions and even the complexity of the decision at hand.

If you ask me, what is the take-home message of those five years of intensive research? I can certainly say that coping with our increasingly complex world with all its ambiguities requires cognitive resources. Today I feel extremely happy that my study has gone some way towards enhancing our understanding of how these processes are encoded at the neural level and allows us to further investigate conditions (age, emotions, etc.) that promote such cognitive learning processes.

But if you ask me, is this the only thing you are happy about your PhD project? I would shout NO!  I feel glad and privileged that I had a great team, an extremely supportive supervisor-mentor, and many inspiring scientists around me. During my interdisciplinary projects, I learnt a lot during my collaboration with mathematicians, data scientists, and psychologists. I loved the inclusive and diverse environment we were creating every single day in the lab, at the corridors, or at our coffee breaks. During the PhD period there is a remarkably high level of uncertainty, on top of self-doubt and workload. As we got to know here, uncertainty equals higher brain activity. This means that you learn, you grow, and you become flexible and able to overcome hurdles. Thus, keep always in mind that your surrounding matters, your time matters, your dreams matter. Go and take the whole PhD-Research experience, it is worth your brain activity.

[1] From the book “Behave – The biology of humans our best and worst, Chapter 1 – The behavior

[2] From the orginal publication Zempeltzi et al. 2020, https://www.nature.com/articles/s42003-020-1073-3