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New brain researcher to join NIEHS

By Emily Zhou
November 2010

Serena Dudek, Ph.D., Douglas Caruana, Ph.D., and Maile Henson, Ph.D.
From left to right are Dudek, Caruana, and Maile Henson, Ph.D., a postdoctoral fellow currently working in Dudek's group. (Photo courtesy of Steve McCaw)

Douglas Caruana, Ph.D., currently a postdoctoral fellow with Zafar Bashir, Ph.D., at the Medical Research Council Center for Synaptic Plasticity at the University of Bristol in the United Kingdom, spoke at NIEHS Oct. 1 as part of the Laboratory of Neurobiology weekly seminar. As it turned out, the talk became an on-site interview for Caruana to pursue a visiting fellow position in the Synaptic and Developmental Plasticity Group, led by Serena Dudek, Ph.D.

"I was very pleased with his profound expertise and broad knowledge in medial prefrontal cortex (mPFC) and other brain regions, so I offered him the position very quickly," Dudek said excitedly. "His expertise fits very well into what we want to investigate, and we believe having him here will benefit our group profoundly."

Caruana accepted the offer, and he will join the NIEHS team sometime in January 2011. Because so little is known about functions of the hippocampal Cornu Ammonis 2 (CA2) region of the brain, Dudek's group plans to explore the role of CA2 in memory formation and social behavior. Previous work from other labs using CA2-enriched gene knock outs resulted in either memory enhancement or deficits in social behavior. The finding led Dudek to speculate that CA2 plays a role in autism.

"With [Caruana] on board, our research will progress forward in CA2 functions," she added. "No doubt, this new addition will pump in fresh blood for neuroscience research at NIEHS."

Object-in-place associative memory

Caruana is an expert electrophysiologist who works with both in vivo and in vitro preparations of rat parahippocampal and neocortical areas. He uses field potential recordings in conscious and anesthetized rats, as well as whole-cell current- and voltage-clamp recordings in brain slices, to investigate the cellular mechanisms underlying memory storage. 

His seminar titled "Everything in its right place: A role for long-term synaptic depression in the formation of object and place associations," opened with a picture of a room filled with different objects occupying specific spatial locations. He asked the audience, "How do we know what objects are there and where they are placed?" Caruana explained that the "what" information is controlled by the perirhinal cortex of the brain, and the "where" information is mediated by the hippocampus.

"Forming associations between objects and places is thought to be mediated by the mPFC, and mPFC receives prominent input from the hippocampus and perirhinal cortex, thereby forming a neural circuit which plays an important role in memory and learning," Caruana explained. He and others in the field hypothesized that changes in synaptic strength in the mPFC may underlie the formation of object and place associations.

Molecular mechanism

According to Carauna, cholinergic innervation of the mPFC has been implicated in many cognitive functions and pathological conditions. Using whole cell voltage clamp recordings of intracellular excitatory postsynaptic currents, he identified a form of long-term synaptic depression mediated by activation of muscarinic acetylcholine receptors and activity of protein kinase C.

Changes in cholinergic transmission may play a critical role in the formation of object and place associations, by inducing lasting plasticity in the mPFC. He said that combined behavioral and electrophysiological studies will examine whether acetylcholine-dependent synaptic depression is involved in the formation of object and place associations.

(Emily Zhou, Ph.D., is a research fellow in the NIEHS Laboratory of Signal Transduction Inositol Signaling Group.)

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