Research focuses on providing for early diagnosis to ameliorate memory loss and attention deficit
Alzheimer's is a frightening disease that takes away so much of what is precious to us - our memories and connections to others. Within the brain, it is the cholinergic cells in the basal forebrain that are destroyed. Along with memory loss, it is suspected that these cells also are linked with attention and our ability to filter the right stimuli so we can appropriately respond to the world around us. That is another facility lost in Alzheimer’s, making the cholinergic cells an especially important key to slowing down the disease's progression.
In his lab, Laszlo Zaborszky, professor of neuroscience at the Center for Molecular and Behavioral Neuroscience, is studying the neural circuitry cholinergic cells develop to provide an early detection method for Alzheimer's.
"Once neurons degenerate, it’s difficult to reverse the process," notes Zaborszky. "But if we can construct a model that allows us to predict how the disease progresses so we can identify when cholinergic cells begin deteriorating, then we may be able to provide for earlier diagnosis."
Although a cure has yet to be found, an early diagnosis would allow the remaining cholinergic cells to be stimulated so progression of the disease can be slowed down before the point where corrections become impossible.
Everything we see, hear, smell, touch and taste is translated into neural stimuli in the brain's prefrontal cortex. The basal forebrain then amplifies important stimuli and suppresses non-essential stimuli, projecting the important information to various cortical areas, making it possible for us to form memories and pay attention to what needs to be attended to, while disregarding non-essential signals. When that system is hindered through the destruction of cholinergic cells as seen in Alzheimer's, it becomes difficult to perform even such simple tasks as putting together a grocery list.
Working with the German research institute, the C. & O. Vogt Institute for Brain Research in Duesseldorf, Zaborszky's lab mapped the basal forebrain cells from postmortem human brains so they can be compared to activations in the brains of living people. His goal is to develop a method to determine when there is a decrease in function in cholinergic cells so measures can be taken to ameliorate the cognitive disorders associated with Alzheimer’s and other forms of dementia.
Along with that research, he also is seeking to determine why cholinergic cells are more susceptible to degeneration than other brain cells. Two possibilities, he says, may be their genetic makeup or the nature of the connections the cells make with other cells. By recording the firing of these neurons in anaesthetized animals and reconstructing those connections through computational techniques, Zaborszky and his lab associates are creating a 3D map to better study the function of neurons in the basal forebrain and the communication patterns cholinergic cells establish among other neurons within the basal forebrain and various cortical areas. Those patterns, he explains, "are far more complex than other neural circuitry within the brain, but their 3D reconstruction can begin to shed light on their organization." Gaining insight into that organization could potentially then open the way for better understanding what makes cholinergic cells more susceptible to degeneration.
Born in Hungary, Laszlo Zaborszky received his M.D. at Semmelweis University, Hungary and his Ph.D. and DSc. from the Hungarian Academy of Sciences. Prior to joining the Center for Molecular and Behavioral Neuroscience at Rutgers University in 1993 as one of the center’s first professors, he was an associate professor in the Department of Neurology at the University of Virginia. He also has held faculty positions at Semmelweis University Hungary, the University of Würzburg, and the Max Planck Institute in Gottingen, Germany.
He has published over 90 scientific papers, including a monograph on hypothalamic connections (Springer, 1982) and is co-editor of the textbook Neuroanatomical Tract-Tracing Methods 2 (Plenum, 1989) and Neuroanatomical Tract-Tracing 3: Molecules, Neurons, Systems (Springer, 2006). He is founding editor-in-chief of Brain Structure and Function, former managing editor of Anatomy and Embryology (2004-2006), and former board member (1994-2000) of the Journal of Chemical Neuroanatomy. He is an elected foreign member of the Hungarian Academy of Sciences.
- Neurons in the Basal Forebrain Project to the Cortex in a Complex Topographic Organization that Reflects Corticocortical Connectivity Patterns: An Experimental Study Based on Retrograde Tracing and 3D Reconstruction, Cerebral Cortex, Aug. 19, 2013
- Intrinsic voltage dynamics govern the diversity of spontaneous firing profiles in basal forebrain noncholinergic neurons, Journal of Neurophysiology, July 2012
- Adult mouse basal forebrain harbors two distinct cholinergic populations defined by their electrophysiology, Frontiers in Behavioral Neuroscience, May 8, 2012
- Volume of the human septal forebrain region is a predictor of source memory accuracy, Journal of the International Neuropsychological Society, Jan. 2012
- The basal forebrain cholinergic projection system in mice (chapter), The Mouse Nervous System, Elsevier Inc., Amsterdam, 2011
- Clustering of large cell populations: Method and application to the basal forebrain cholinergic system, Journal of Neuroscience Methods, Dec. 15, 2010
- Reduction of basal forebrain cholinergic system parallels cognitive impairment in patients at high-risk to develop Alzheimer’s disease, Cerebral Cortex, November 4, 2009
- Vesicular glutamate transporter 1 and vesicular glutamate transporter 2 synapses on cholinergic neurons in the sublenticular gray of the rat basal forebrain: a double-label electron microscopic study, Neuroscience, December, 29, 2009
- Stereotaxic probabilistic maps of the magnocellular cell groups in human basal forebrain, NeuroImage, September 1, 2008
- Functional connectivity of the brain: Reconstruction from static and dynamic data, in Neuroanatomical Tract-Tracing 3, Springer, New York, 2006
- Three-dimensional chemoarchitecture of the basal forebrain: spatially specific association of cholinergic and calcium binding protein-containing neurons, Neuroscience, 2005, 136:697-713
- Vglut2 afferents to the medial prefrontal and primary somatosensory cortices: A combined retrograde tracing in situ hybridization study, The Journal of Comparative Neurology, May 23, 2005
- Sleep-wake mechanisms and basal forebrain circuitry, Frontiers in Bioscience, September 1, 2003
- EEG correlation of the discharge properties of identified neurons in the basal forebrain, Journal of Neurophysiology, 2000, 84: 1627-1635
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