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Nicotine effects on neurological development

Institution: University of California, Irvine
Investigator(s): Raju Metherate, Ph.D.
Award Cycle: 1999 (Cycle 8) Grant #: 8RT-0059 Award: $189,233
Subject Area: Nicotine Dependence
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
A particularly tragic effect of tobacco smoke is what it does to unborn and newborn babies, including how it affects their brain growth. Nicotine in a mother's bloodstream can cross the placenta to affect brain development in the fetus. Even after birth, nicotine in secondhand smoke inhaled by infants can affect their growing brains. For example, studies have shown that smoking by pregnant mothers results in babies that do not respond as well as they should to sounds around them. As a result, their abilities later on in life to hear and speak normally are hurt. Since these babies have normal input from their ears to their brain, their problems come from improper brain development. Similar problems also occur in infants who inhale secondhand smoke. It is not known why nicotine has this effect, nor is it known how much nicotine must be inhaled in order to produce these effects. This research will determine how exposure to nicotine affects the normal development of the auditory cortex (the highest brain center responsible for hearing). Scientists think that a protein called the NMDA receptor is important for the development of the auditory cortex (and similar areas for sight and touch). Recent studies have shown that nicotine affects the normal functions of the NMDA receptor. The effect is strongest during a brief period of time shortly after birth. This may be the time when the growing brain is most vulnerable to the effects of tobacco smoke. By placing tiny electrodes into brain cells to measure their activity, we will determine exactly how nicotine affects the NMDA receptor. We will also determine how much exposure to nicotine is sufficient to affect brain growth. Finally, we will test auditory functions in adult rats that were exposed to nicotine as pups, to determine how exposing babies to nicotine will affect their abilities as they age. This research will benefit the public by increasing our understanding of how nicotine affects brain function.
Publications

In vivo hebbian and basal forebrain stimulation treatment in morphologically identified auditory cortical cells
Periodical: Brain Research Index Medicus:
Authors: Cruikshank SJ, Weinberger NM ART
Yr: 0 Vol: Nbr: Abs: Pg:

Differential modulation of auditory thalamocortical and intracortical synaptic transmission by cholinergic agonist
Periodical: Brain Research Index Medicus:
Authors: Hsieh CY, Cruikshank SJJ, Metherate R ART
Yr: 2000 Vol: 880 Nbr: 1-2 Abs: Pg: 51-64

Thalamocortical inputs trigger a propagating envelope of gamma-band activity in auditory cortex
Periodical: Experimental Brain Research Index Medicus:
Authors: Metherate R, Cruikshank SJ ART
Yr: 1999 Vol: 126 Nbr: Abs: Pg: 160-174

Evidence for the hebbian hypothesis in experience-dependent physiological plasticity of neocortex: a critical review
Periodical: Brain Research Reviews Index Medicus:
Authors: Cruikshank SJ, Weinberger NM ART
Yr: 1996 Vol: 22 Nbr: 3 Abs: Pg: 191-228

Receptive field plasticity in adult auditory cortex induced by hebbian covariance
Periodical: Journal of Neuroscience Index Medicus:
Authors: Cruikshank SJ, Weinberger NM ART
Yr: 1996 Vol: 16 Nbr: 2 Abs: Pg: 861-875

A critical period for nicotine-induced disruption of synaptic development in rat auditory cortex
Periodical: Journal of Neuroscience Index Medicus:
Authors: Aramakis VB, Hsieh CY, Leslie FM, Metherate R ART
Yr: 2000 Vol: 10 Nbr: Abs: Pg: 6106-6116

In vitro physiological comparison of MGv inputs to layer 3/4 of auditory cortex vs nonlemniscal inputs to layer 1
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Cruikshank SJ, Rose HJ, Metherate R ABS
Yr: 1999 Vol: 25 Nbr: 2 Abs: Pg: 1665

Complementary distributions of parvalbumin and calbindin in subregions of mouse auditory thalamus
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Killackey HP, Cruikshank SJ, Metherate R ABS
Yr: 1999 Vol: 25 Nbr: 2 Abs: Pg: 1419

Cholinergic agonist differentially suppresses auditory thalamocortical and intracortical transmission
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Hsieh CY, Cruikshank SJ, Metherate R ABS
Yr: 1998 Vol: 24 Nbr: 2 Abs: Pg: 1879

Hebbian induction of auditory cortical receptive field plasticity: effect of number of trials and cortical state
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Cruikshank SJ, Weinberger NM ABS
Yr: 1995 Vol: 21 Nbr: 3 Abs: Pg: 1927

Excerpts from the professional correspondence of Ralph Waldo Gerard
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Cruikshank SJ ABS
Yr: 1995 Vol: 21 Nbr: 1 Abs: Pg: 245

Parvalbumin and calbinden are differentially distributed within primary and secondary subregions of mouse auditory forebrain
Periodical: Neuroscience Index Medicus:
Authors: Cruikshank SJ, Killackey HP, Metherate R ART
Yr: 2001 Vol: 105 Nbr: Abs: Pg: 553 - 569

Expression of NMDA receptor subunit mRN in developing rat auditory cortex and thalamus
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Hsieh CY, Leslie FM, Metherate R ABS
Yr: 2001 Vol: Nbr: Abs: 27 Pg:

Nicotine exposure during a postnatal critical period alters NR2A and NR2B mRNA expression in rat auditory forebrain.
Periodical: Developmental Brain Research Index Medicus:
Authors: Hsieh CY, Leslie FM, and Metherate R ART
Yr: 2002 Vol: 133 Nbr: Abs: Pg: 19 - 25

Organization of functional donnectivity in rat primary auditory cortex: a potential mechanism for broad spectral integration.
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Kaur S, Lazar R, Liang K, and Metherate R ABS
Yr: 2002 Vol: Nbr: A458.5 Abs: 28 Pg: