An interview with Dr Linda Wilbrecht, Associate Professor, UC Berkeley, conducted by April Cashin-Garbutt, MA (Cantab)

How might adolescence change learning and decision-making?

There are dramatic changes in neural circuits, particularly in frontal cortical and basal ganglia circuits during adolescence. We believe that these changes adjust and tune the brain in order to sculpt learning and decision-making at these different life stages.

People often deride the function of the frontal cortex in teenagers. We believe the frontal cortex is quite functional in teenagers, but it is doing something different than it is doing in adults.

How does the function of the frontal cortex differ in teenagers and adults?

Adolescents have so much less experience and they are in the middle of gathering all sorts of experience in order to adjust into adult roles. We believe that there may be unrecognised aspects to learning that help people to become independent from their parents and to develop their independent identity.

There might be something similar in mice because they have to disperse from their natal environment, navigate a completely new environment and then develop their own habits and routines before they find a mate.

It is clear in mice that they have to survive this risky period and so they might have special adaptations for dispersal and learning prior to becoming reproductive.

How do you study the influence of puberty on behaviour and circuit development?

We have been manipulating the onset of puberty, driving earlier timing, and then blocking puberty altogether.

We also work with wild mice who seasonally regulate their reproductive cycle and if they are born on short days, they overwinter before going through puberty and so we are looking at how the brain is different in these wild mice that were born in different seasonal light cycles.

Is it true that puberty in humans is accelerating and do we know why this might be happening?

Human puberty has been accelerating, particularly in girls, over the last century by many years. It is not yet clear if this is important or not for learning and education, but it does come with many negatives, particularly increasing risks for mental illness in girls.

There is a lot of speculation around the reasons why human puberty might be accelerating, but one theory is that it is related to diet.

How have recent optogenetic and chemogenetic manipulation experiments increased understanding of flexible choice behaviour?

We have been really lucky to be doing our science in a time where we have the capacity to make causal manipulations.

We have been finding that our heuristic models aren't always supported by the data that we find by optogenetically and chemogenetically manipulating the circuit and we are having to rely more and more on computational models to understand the outcome of our experiments.

This research is leading us to insights that we maybe would not have made if we were just recording from neurons and imagining what they do.

What can impairments in reversal learning teach us about psychiatric disorders?

Disruptions of cognitive flexibility are core features of multiple psychiatric disorders including addiction, mania and bipolar disorder. Inflexibility is also a part of OCD and schizophrenia. Cognitive flexibility is therefore critical aspect of mental health.

It is interesting to note that a form of cognitive flexibility, reversal learning, is different than extinction learning and may rely on different mechanisms. Extinction training (which is studied in the lab and used in therapy) asks the brain to  suppress a behaviour entirely, “cold turkey”. Reversal learning involves replacing one goal or one behavior with another.

I think this replacement might be important when I see the popularity of addiction treatments like Alcoholics Anonymous (AA) meetings, where people replace one pattern of behaviour, such as going to the pub, with going to an AA meeting. I don’t how well it has been tested yet, but it would be interesting to know if addiction treatments might do better when they rely more on reversal than extinction mechanisms.

What is the next piece of the puzzle your research is going to focus on?

We have been looking at the mechanisms of decision-making in adult animals and how the brain changes through development in adolescent animals. It has been difficult to put these studies fully together to map which are the causal mechanisms changing during development that guide the behavioural changes in decision-making in adolescence.

Most of the mechanistic understanding we have as a field comes from adult animals. We have yet to decipher which moving pieces in development are the critical ones for the changes in behaviour.

How do you hope to work out the causal mechanisms?

One, using manipulation experiments. Two, we are interested in how the experience of the animal changes the system. A large part of our work is on how austere environments that mimic elements of poverty affect brain development.

Where can readers find more information?

Further information can be found on my lab website.

Here is the link to the Center for the Developing Adolescent.

There was a special article collection in Nature recently called Coming of Age, where we contributed an article.

About Dr Linda Wilbrecht

In my lab, we focus on the development and function of the prefrontal cortex and basal ganglia and their role in feedback based learning, behavioural flexibility, decision-making, and substance use. We use in vivo imaging and in vivo and ex vivo electrophysiology to investigate developmental and experience-dependent changes in neural circuits and optogenetics and DREADDs to test how changes in neural activity may influence behaviour in mouse models. 

We have a particular interest in the period of adolescence as a potential sensitive period for brain development. We study the influence of different forms of adversity and pubertal timing on behaviour and circuit development at this time in both human subjects and rodent models. I am also a founding member of the Center on the Developing Adolescent whose mission is to improve adolescent health, education, and well-being through developmental science by building bridges between research, programs, and policy.