Alison L. Barth Associate Professor Ph.D., University of California, Berkeley Postdoctoral Appointment, Stanford University School of Medicine barth@cmu.edu 412-268-1198 (Phone) 412-268-8423 (Fax) 159C Mellon Institute Department of Biological Sciences Carnegie Mellon University 4400 Fifth Avenue Pittsburgh, PA 15213

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Research in the lab centers around one overriding question: how does experience selectively activate and change neuronal properties? Although we are beginning to understand the neural basis for discrete behaviors in invertebrates, this question is exponentially more complex and challenging in vertebrates. In the mammalian cortex, complex behaviors and learning are mediated through the activity of hundreds of thousands -- if not millions -- of the trillions of neurons. Finding the right brain area, and indeed, the right neurons, is a critical step in enabling to identify the cellular and molecular basis for behavioral plasticity. We are addressing this question using a novel strain of transgenic mice that express GFP under the control of the c-fos promoter (fosGFP transgenic mice), coupling fluorescent gene expression to neural activity. This technique has allowed us to focus on changes occurring in the neurons that have initiated gene expression in response to in vivo experience. Once we know where in the brain to look, it becomes possible to ask highly sophisticated questions that bring together systems-level neuroscience, cellular electrophysiology, and molecular biology.

Specific Projects

1. Identifying the plasticity transcriptome. It has long been recognized that learning requires the transcription of new genes, and there is abundant experimental evidence supporting a role for two transcription factors, CREB and zif268/egr-1, in initiating activity-dependent transcription. After identifying CREB and zif268 gene targets, we are now interested in how these targets are regulated by neuronal activity in seizure disorders and learning.
2. Cortical plasticity underlying epileptogenesis.  Understanding how brain activity is abnormal after seizures can lead to the development of new anticonvulsant therapies. We have identified several new ion channels that are functionally enhanced after seizures and are using these targets to develop anticonvulsant therapies.  In addition, we are interested in how seizures themselves initiate a program of plasticity that might facilitate later abnormalities.
3. Cellular and synaptic mechanisms of sensory plasticity.  Sensory plasticity driven by whisker stimulation grows over days to weeks, altering neural function from the synapse to the entire circuit.  Using fosGFP expression to identify the precise area of the brain that has been activated by sensory input, we can use the powerful tools of in vitro slice electrophysiology to investigate the cellular and synaptic consequences of sensory-driven plasticity.  What are the molecular pathways involved in initiating and accumulating changes in synaptic strength?  How do neurons and circuits change their excitability and connectivity?  How do these changes impact the computational properties of individual neurons and the cortical column?   In addition, we have begun to examine the effect of this type of sensory plasticity on perceptual capacities as well as sensory-dependent learning in vivo. 

Selected Publications

Barth AL and Wheeler ME. The barista on the bus: cellular and synaptic mechanisms for visual recognition memory. Neuron 24, 58(2):159-61, 2008.

Shruti S, Clem RL and Barth AL. A seizure-induced gain-of-function in BK channel is associated with elevated firing activity in neocortical pyramidal neurons. Neurobiology of Disease, 30(3):323-30, 2008.

Clem RL and Barth AL. Ongoing in vivo experience triggers synaptic metaplasticity in the neocortex. Science, 319: 101-104, 2008.

Barth AL. Visualizing circuits and systems using transgenic reporters of neural activity. Current Opinion in Neurobiology, 2007. (epub Nov 23 2007)

Glazewski S, Benedetti BL and Barth AL. Ipsilateral sensory deprivation enhances cortical plasticity. Journal of Neuroscience, 27 (14): 3910-20, 2007.

Pfenning AR, Schwartz R and Barth AL.  A comparative genomics approach to identifying the plasticity transcriptome. BMC Neuroscience, 8: 20, 2007.

Clem RL and Barth A.  Pathway-specific trafficking of native AMPARs by in vivo experience. Neuron, 2;49 (5): 663-70, 2006.

Barth AL, Gerkin RC and Dean KL.  Alteration of neuronal firing properties in a fosGFP transgenic mouse. Journal of Neuroscience, 24: 6466-6475, 2004.