Wilbrecht Lab

Research

Developmental and experience-dependent changes in learning and decision making

The frontal regions of the neocortex show protracted development in mammals. While dendritic spines are pruned in the frontal neocortex in adolescence there is also late growth of new local and long range connections. We are interested in understanding the function of these changes and their impact on learning and decision making.

Current projects in the lab are focused on these questions:

How does experience in development alter the way the adult brain learns and makes decisions? Does experience with adversity in maternal care or food insecurity alter brain function? How does early learning experience with different statistics alter later circuit function? How does early life adversity enhance risk of substance use issues?

How does pubertal onset alter circuit function, learning and decision making?

How do cortico-basal ganglia circuits support learning and flexible decision making? How do genes x experience sculpt the computations made by these circuits.

How do different learning systems mature? How are these learning systems integrated through development? (with Anne Collins lab)

What changes in the brain support dispersal from the natal nest in rodents? Do we see any similar changes in humans and how does this inform our understanding of adolescent development?

We are also collaborating with the Markita Landry lab to develop new optical tools for neuroscience.

Approaches

In Vivo Imaging

We use in vivo imaging methods to examine the function of specific cell types during behavior. We are particularly interested in the neurons that regulate learning and flexible updating of behavior in the neocortex and basal ganglia.

Electrophysiology

We use electrophysiology to investigate the changes in neurotransmission at different developmental stages and in rodents with different experience. We also use new optical tools to measure neuromodulator release in brain slice preparations.

Behavior

We use behavioral tests to investigate learning and decision making at different stages of development and in animals with different experiences. We are particularly interested in cognitive flexibility.

Recent Publications & Preprints

The interpretation of computational model parameters depends on the context

Reinforcement Learning (RL) models have revolutionized the cognitive and brain sciences, promising to explain behavior from simple conditioning to complex problem solving, to shed light on developmental and individual differences, and to anchor cognitive processes in specific brain mechanisms. However, the RL literature increasingly reveals contradictory results, which might cast doubt on these claims. We hypothesized that many contradictions arise from two commonly-held assumptions about computational model parameters that are actually often invalid: That parameters generalize between contexts (e.g. tasks, models) and that they capture interpretable (i.e. unique, distinctive) neurocognitive processes. To test this, we asked 291 participants aged 8–30 years to complete three learning tasks in one experimental session, and fitted RL models to each. We found that some [...]

The maturation of exploratory behavior in adolescent Mus spicilegus on two photoperiods

Dispersal from the natal site or familial group is a core milestone of adolescent development in many species. A wild species of mouse, Mus spicilegus, presents an exciting model in which to study adolescent development and dispersal because it shows different life history trajectory depending on season of birth. M. spicilegus born in spring and summer on long days (LD) disperse in the first 3 months of life, while M. spicilegus born on shorter autumnal days (SD) delay dispersal through the wintertime. We were interested in using these mice in a laboratory context to compare age-matched mice with differential motivation to disperse. To first test if we could find a proxy for dispersal related behavior in the laboratory environment, we measured open field and novel [...]

Activation, but not inhibition, of the indirect pathway disrupts choice rejection in a freely moving, multiple-choice foraging task

The dorsomedial striatum (DMS) plays a key role in action selection, but less is known about how direct and indirect pathway spiny projection neurons (dSPNs and iSPNs, respectively) contribute to choice rejection in freely moving animals. Here, we use pathway-specific chemogenetic manipulation during a serial choice foraging task to test the role of dSPNs and iSPNs in learned choice rejection. We find that chemogenetic activation, but not inhibition, of iSPNs disrupts rejection of nonrewarded choices, contrary to predictions of a simple “select/suppress” heuristic. Our findings suggest that iSPNs’ role in stopping and freezing does not extend in a simple fashion to choice rejection in an ethological, freely moving context. These data may provide insights critical for the successful design of [...]

Transient food insecurity during the juvenile-adolescent period affects adult weight, cognitive flexibility, and dopamine neurobiology

A major challenge for neuroscience, public health, and evolutionary biology is to understand the effects of scarcity and uncertainty on the developing brain. Currently, a significant fraction of children and adolescents worldwide experience insecure access to food. The goal of our work was to test in mice whether the transient experience of insecure versus secure access to food during the juvenile-adolescent period produced lasting differences in learning, decision-making, and the dopamine system in adulthood. We manipulated feeding schedules in mice from postnatal day (P)21 to P40 as food insecure or ad libitum and found that when tested in adulthood (after P60), males with different developmental feeding history showed significant differences in multiple metrics of cognitive flexibility in learning and decision-making. [...]