Research

Adolescence typically marks a major transition to independence. Independence brings with it the need to make important decisions, such as where to forage, where to sleep, and when and where to reproduce. It also often requires a period of exploration with high tolerance for risk that is eventually followed by formation of more stable adult habits. In humans, adolescence also marks a critical moment for the development of addiction.

Anatomical studies have shown that the mammalian brain undergoes radical changes during adolescence, particularly in the frontal lobe, which integrates sensory and memory systems and coordinates flexible decision-making. We are focused on understanding the adolescent transition at the synaptic, circuit, and behavioral level. In particular, we want to understand:

How adolescent experience with drugs of abuse and natural reinforcers, such as food, alters neural circuitry and decision-making over the lifespan, and how neural plasticity can be harnessed to reverse addiction.

Approaches

2-Photon Imaging

We employ in vivo 2-photon imaging to follow circuit maturation in individual mice over weeks to months. This technology allows ‘time-lapse’ measurement of the effect of age, drugs and other kinds of experiences on individual axons, dendrites, and spines.

Electrophysiology

We also use electrophysiology to investigate the capacity for plasticity in limbic and frontal circuits in rodents at different developmental stages. These experiments focus on the effect of age and neuromodulators on the capacity for change in synaptic strength at both excitatory and inhibitory synapses.

Behavior

We use behavioral tests to investigate the decision rules used by rodents at different stages of development and with different experiences.

Recent Publications

  • Long-range orbitofrontal and amygdala axons show divergent patterns of maturation in the frontal cortex across adolescence

Long-range orbitofrontal and amygdala axons show divergent patterns of maturation in the frontal cortex across adolescence

  • February 3rd, 2016

The adolescent transition from juvenile to adult is marked by anatomical and functional remodeling of brain networks. Currently, the cellular and synaptic level changes underlying the adolescent transition are only coarsely understood. Here, we use two-photon imaging to make time-lapse observations of long-range axons that innervate the frontal cortex in the living brain. We labeled cells in the orbitofrontal cortex (OFC) and basolateral amygdala (BLA) and imaged their axonal afferents to the dorsomedial prefrontal cortex (dmPFC). We also imaged the apical dendrites of dmPFC pyramidal neurons. Images were taken daily in separate cohorts of juvenile (P24–P28) and young adult mice (P64–P68), ages where we have previously discovered differences in […]

  • Rule learning enhances structural plasticity of long range axons in frontal cortex

Rule learning enhances structural plasticity of long range axons in frontal cortex

  • February 3rd, 2016

Rules encompass cue-action-outcome associations used to guide decisions and strategies in a specific context. Subregions of the frontal cortex including the orbitofrontal cortex (OFC) and dorsomedial prefrontal cortex (dmPFC) are implicated in rule learning, although changes in structural connectivity underlying rule learning are poorly understood. We imaged OFC axonal projections to dmPFC during training in a multiple choice foraging task and used a reinforcement learning model to quantify explore–exploit strategy use and prediction error magnitude. Here we show that rule training, but not experience of reward alone, enhances OFC bouton plasticity. Baseline bouton density and gains during training correlate with rule exploitation, while bouton loss correlates with exploration and […]

Lab News

Gopnik on Maternal Separation

  • March 24th, 2016

My colleague Professor Alison Gopnik discusses the Wilbrecht Lab’s work in the Wall Street Journal this week. Gopnik’s article […]

News Coverage on Nature Comms Article

  • March 7th, 2016

Christopher Bergland, How Does Your Brain Learn Through Trial and Error? Problem-solving and critical thinking can rewire the orbitofrontal […]