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Neuroscience Graduate Program at UCSF

Faculty - Linda Wilbrecht, Ph.D.

Adolescent Development of Neural Circuits for Decision-Making


Research Description

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:


Approaches
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.

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.

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

These technologically different approaches will be integrated into larger experiments to shed light on how adolescent experience can affect neural circuit development creating a measurable, long-term change in behavior. New lab members will ideally collaborate and become personally involved with imaging, electrophysiology, and behavioral experiments in pursuit of individual questions.

Addiction

In addition to adolescence, we are also interested in the neurobiology of addiction. As part of the Ernest Gallo Clinic and Research Center, our laboratory is committed to seeking translational applications for basic neuroscience to treat and prevent alcohol and substance abuse. We hope to understand how changes in neural circuits can bias decision-making to facilitate healthy adult habits or create inflexible addictive behavior. These findings should inform strategies to ameliorate addiction by defining the answers to the following questions:

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Current Projects

To be announced

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Lab Members

F. Javier Muñoz-Cuevas, PhD, Postdoctoral Fellow, fmunozcuevas@gallo.ucsf.edu
Lung-Hao Tai, PhD, Postdoctoral Fellow, ltai@gallo.ucsf.edu
Natalia Caporale, PhD, Postdoctoral Fellow, ncaporale@gallo.ucsf.edu
Angela Vandenberg, Graduate Student, avandenberg@gallo.ucsf.edu
Carolyn Johnson, Graduate Student, cjohnson@gallo.ucsf.edu
Moses Lee, Graduate Student, mlee@gallo.ucsf.edu
Hannah Peckler, Research Assistant, hpeckler@gallo.ucsf.edu
Jegath Athilingam, Research Assistant, jathilingam@gallo.ucsf.edu
Claudia Wu, Research Assistant, cwu@gallo.ucsf.edu
Nora Benavidez, Research Assistant, nbenavidez@gallo.ucsf.edu

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Selected Publications

Selected Research Publications:

Johnson C and Wilbrecht L. 2011. Juvenile mice show greater flexibility in multiple choice reversal learning than adults. Dev Cognitive Neurosci. doi:10.1016/j.physletb.2003.10.071. Article (PDF)

Wilbrecht L, Shohamy D. 2010. Neural circuits can bridge systems and cognitive neuroscience. Front Hum Neurosci. 3:81.

Wilbrecht L, Holtmaat A, Wright N, Fox K, Svoboda K. 2010. Structural plasticity supports experience-dependent functional plasticity of cortical circuits. J. Neurosci. 30(14):4927-4932

Holtmaat A, Bonhoeffer T, Chow, Chuckowree J, De Paola V, Hofer S, Hubener M, Keck T,  Lee W-C A, Knott G, Mrsic-Flogel T, Mostany R, Nedivi E, Portera-Cailliau C, Svoboda K, Trachtenberg J,  Wilbrecht L. 2009. Long-term, high-resolution imaging in the mouse neocortex through an imaging window. Nature Protocols 4(8):1128-44.

Wilbrecht L. 2007. Linking Affect to Action: Critical Contributions of the Orbitofrontal Cortex. eBriefing on a New York Academy of Science March 2007 conference:
http://www.nyas.org/Publications/EBriefings/Detail.aspx?cid=2858bfa4-5b54-4254-9f93-f1773a746c70

Holtmaat A*, Wilbrecht L*, Knott G, Welker, E, Svoboda K. 2006. Experience-dependent and cell-type specific spine growth in the neocortex. Nature 441:979-983

Wilbrecht L, Williams H, Gangadhar N, Nottebohm F. 2006. High levels of new neuron addition persist when the sensitive period for song learning is experimentally prolonged. J Neurosci. 26(36):9135-41.

Knott GW, Holtmaat A, Wilbrecht L, Welker E, Svoboda K. 2006. Spine growth precedes synapse formation in the adult neocortex in vivo. Nat Neurosci. 9(9):1117-24.

De Paola V, Holtmaat A, Knott G, Song S, Wilbrecht L, Caroni P, Svoboda K.  2006. Cell type-specific structural plasticity of axonal branches and boutons in the adult neocortex. Neuron. 49(6):861-75.

Holtmaat A, Trachtenberg, JT, Wilbrecht L, Shepherd GM, Zhang XQ, Knott GW, Svoboda K. 2005. Turnover and stability of dendritic spines in the somatosensory and visual cortex in vivo. Neuron. 45(2):279-91.

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Linda Wilbrecht, Ph.D.



Email

lwilbrecht@gallo.ucsf.edu

Phone

510-985-3560

Office Address

Ernest Gallo Clinic & Research Center
5858 Horton Street, Suite 200
Emeryville, CA 94608

Other Websites

Gallo Institute

Wilbrecht Lab

The Wheeler Center for the Neurobiology of Addiction