Ethanol is a potent teratogen that can induce many neural deficits including motor dysfunction, mental retardation and cognitive deficiencies. However, the study of ethanol-induced neural disorders has been difficult due to the complexity of the nervous system, both in its temporal development and its topographical organization. The set of synaptic connections which primary sensory afferents form in the embryonic chick spinal cord provide an excellent system to study the teratogenicity of ethanol anatomically and electrophysiologically at the level of functionally identified neurons. One goal of the present proposal is to use intracellular and extracellular recording, as well as neuroanatomical techniques to define the effect of ethanol on the morphology and pattern of connectivity of chick sensory and spinal motor neurons. These data will: 1) define deficits within the spinal cord that may contribute to ethanol- induced motor dysfunction, and 2) use the sensory afferent to motoneuron monosynaptic connection as a model synapse to describe ETOH-induced abnormalities. Similar alterations in higher neural centers may lead to mental retardation and cognitive deficiencies. Recently, a number of studies have proposed the intriguing possibility that ethanol may act by interfering with the function of N-methyl-D-aspartate (NMDA) receptors (Lovinger et al., '89; Hoffman et al., '89). Interestingly, blocking NMDA receptors during normal development is known to alter the formation of somatotopic maps of sensory information in the brain (Cline and Constantine-Paton, '89; Bear et al., '90). Most primary sensory afferents involved in chick spinal cord neural circuits use an excitatory amino acid neurotransmitter that activates NMDA receptors. Preliminary data from the proposed study indicate that embryonic ETOH exposure produces changes in sensory afferent arbors in the spinal cord similar to those induced by blocking NMDA receptors in the visual system. Therefore, another goal of the present proposal is to use the chick spinal cord to test the hypothesis that some of the developmental abnormalities induced by ETOH are mediated by blocking NMDA receptor function. The importance of the proposed research is at least threefold: 1) it will describe changes in spinal cord circuitry that may contribute to ETOH- induced motor dysfunction 2) it will help elucidate some of the mechanisms by which fetal alcohol exposure can lead to permanent nervous system damage; and 3) it will establish the embryonic chick spinal cord preparation as a system where the neuroteratogenetic deficits of fetal alcohol exposure can be studied and potential treatments of these deficits can be tested.
| Muramoto, T; Mendelson, B; Phelan, K D et al. (1996) Developmental changes in the effects of serotonin and N-methyl-D-aspartate on intrinsic membrane properties of embryonic chick motoneurons. Neuroscience 75:607-18 |
| Mendelson, B; Driskill, A (1996) Ethanol exposure alters the development of serotonergic neurons in chick spinal cord. Alcohol 13:431-41 |
| Mendelson, B; Albers, K M; Goodness, T P et al. (1996) Overexpression of nerve growth factor in epidermis of transgenic mice preserves excess sensory neurons but does not alter the somatotopic organization of cutaneous nerve projections. Neurosci Lett 211:68-72 |
| Mendelson, B (1994) Chronic embryonic MK-801 exposure disrupts the somatotopic organization of cutaneous nerve projections in the chick spinal cord. Brain Res Dev Brain Res 82:152-66 |
