Research

dendritogenesis

Correct neuronal growth during early brain development is crucial to creating appropriate neural network structures necessary for all brain functions. Work from our laboratory and others finds that neuronal activity, including that driven by natural sensory experience directs dendrite growth to create neural network structures optimally tuned to process that information. The period of neuronal growth involves dramatic morphological plasticity as neurons rapidly extend and retract processes seeking correct neurons to contact. Once neurons mature, they largely loose the ability to change their arbor structures. Abnormal brain neuronal growth due to disease-associated gene expression or insufficient or excessive neuronal activity therefore may produce persistent neural network malformations and lasting dysfunction underlying developmental brain disorders.

In the Haas Lab we directly image neuron growth within the intact and awake embryonic brain. We image both rapid growth dynamics over seconds to minutes, and long term changes over days, to investigate mechanisms underlying normal and abnormal neuronal development.

a normal neuron (left), and a neuron demonstrating abnormal growth under reduced glutamate receptor function (right)

schizophrenia

how does reduced glutamatergic transmission affect dendrite growth?

Schizophrenia is associated with glutamate hypo-function. We use direct in vivo imaging of brain neuron growth under conditions of reduced glutamatergic transmission to investigate whether abnormal brain structures are formed.

Picture shows a normal neuron (left), and a neuron demonstrating abnormal growth under reduced glutamate receptor function (right).

Haas, PNAS 2006 download

autism

role of the cell adhesion molecules neurexin and neuroligin in dendritogenesis

The cell adhesion molecules Neurexin and Neuroligin play important roles in synapse formation and maturation. Mutations in both have been identified in families with Autism Spectrum Disorders (ASDs) suggesting a synaptic abnormality contributing to this disorder. By manipulating Neuroexin/Neuroligin function we investigate whether they also play a role in dendrite growth within the developing brain, potentially identifying a neuronal structural abnormality in ASDs.

epilepsy

effects of seizures on brain development

The developing brain is exceptionally prone to seizures at stages when neuronal growth is directed by network activity. We are investigating how seizures alter growth by directly imaging developing neurons during experimentally induced seizures within the intact and awake brain. Using comprehensive analysis of brain neuron growth dynamics, we find acute and long lasting affects on neuronal morphology.

Hewapathirane, Exp. Neurol 2008 download

developmental neuronal plasticity

molecular pathways underlying activity-dependent dendrite growth

Using single-cell electroporation for controlling gene expression in individual neurons within the intact developing brain we are dissecting the molecular pathways mediating developmental brain plasticity. Our findings that the kinase PKMz regulates dendritic arbor growth suggests that developmental morphological plasticity employs the same molecular mechanisms that underlie synapse plasticity, learning and memory in the mature brain.

Liu, J. Neurosci 2009 download

neural network plasticity

Using rapid two-photon imaging and calcium sensitive dyes as indicators of neuronal firing we can sample activity of 100s of neurons within the intact and awake developing brain. We explore how developing brain neural networks encode sensory information and how this encoding changes in response to plasticity inducing training.

Dunfield, Neuron 2009 download