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Lorna W. Role, PhD

Professor

E-mail: lwr1@columbia.edu


Synaptogenesis, signaling and expression of nAChRs, mechanisms and circuits involved in drugs of abuse:

Role 
picture The major emphasis of Dr. Role's laboratory is on the mechanisms underlying the maturation and maintenance of synapses between neurons. She and her colleagues have investigated the inductive inter-action between pre- and postsynaptic neurons that result in the initial expression and long-term changes in the transmitter-gated channels required for continued synaptic function. Their work uses slice preparations of specific brain regions. Identified central and peripheral neurons are maintained in vitro with presynaptic input. These preparations allow direct visualization as well as biophysical and molecular analyses of the initial events in synapse formation. The early work of Dr. Role's group on the developmental regulation of receptor expression reveals that, even before innervation, cholinoceptive neurons express several functionally distinct subtypes of acetylcholine receptor (AChR) channels. Innervation induces changes in the biophysical properties and distribution of these channels. More recent work has pursued the molecular basis of the biophysically detected changes in AChR function, examining the regulation of expression of the various AChR subunit genes and, by using gene deletion techniques (including antisense oligonucleotides), assessing the functional role of the individual subunit gene products. Her current studies aim 1) to identify the signaling molecules responsible for expression of nAChRs and differentiation of cholinoceptive neurons; and 2) to elucidate the mechanisms/circuits involved in drugs of abuse such as nicotine. There is growing evidence that central nicotinic AChRs may participate in memory formation. Several studies have implicated alterations in cholinoceptive neurons in memory and attention, e.g. involvement in Alzheimer's, Parkinson's, and schizophrenia.



Selected publications
Girod R, Role LW. 2001. Long-lasting enhancement of glutamatergic synaptic transmission by acetylcholine contrasts with response adaptation after exposure to low-level nicotine. J Neurosci. 21(14):5182-90.

Barazangi N, Role LW. Nicotine-induced enhancement of glutamatergic and gabaergic synaptic transmission in the mouse amygdala. J Neurophysiol. 86(1):463-74.

Du C, Role LW. 2001. Differential modulation of nicotinic acetylcholine receptor subtypes and synaptic transmission in chick sympathetic ganglia by pge(2). J Neurophysiol. 85(6):2498-508.

Wolpowitz D, Mason TB, Dietrich P, Mendelsohn M, Talmage DA, Role LW. 2000. Cysteine-rich domain isoforms of the neuregulin-1 gene are required for maintenance of peripheral synapses. Neuron. 25(1):79-91.

Bao J, Talmage DA, Role LW, Gautier J. 2000. Regulation of neurogenesis by interactions between HEN1 and neuronal LMO proteins. Development. 127(2):425-35.

Lorna W. Role's Medline citations



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Last modified on August 8, 2001