INFLUENCING NEURONAL SURVIVAL AND REGROWTH BETWEEN NEURONS AND NON-NEURONAL CELLS
ALBERT J. AGUAYO Center for Research in Neuroscience,
In the peripheral nervous system, normal Schwann cells that differentiate towards a myelinating phenotype express several neurotrophins in response to injury. Such molecules can increase the viability of nerve cells and the lengthening of their nerve fibers and terminal branches. When Schwann cell transplants are used experimentally in adult mammals as substitutes of CNS glia, the injured CNS axons can regenerate long distances and form new functional synapses with distant targets. Such effects of Schwann cells on CNS regeneration may be influenced by secreted growth factors, which are normally not expressed by glia in the adult CNS. The neuroprotective role of non-neuronal cells in the CNS, however can be enhanced both in vitro and in vivo by targeting gene expression to CNS glia via vectors such as adenoviruses. For Ml ler cells in the rat retina were infected with an Ad.BDNF vector injected intravitreally. this purpose, The cellular localization of the gene product was facilitated by the use of a c-myc-BDNF viral construct under the control of the CMV promoter. The Ml ler cells of these animals were shown to selectively express BDNF for approximately 10 days after infection but when such rats were treated systemically with the immune-suppressant FK-506 the mutant gene product remained biologically active for at least one month. Ml ler cell-mediated BDNF expression transiently rescued retinal ganglion cells (RGCs) from axotomy-induced apoptosis but the long-term survival of these neurons was apparently curtailed by axotomy-related changes in neuronal responsiveness to the available BDNF. Thus, Schwann cell transplants and vector mediated gene expression in CNS glial cells can be useful tools to modify the interactions between neurons and nonneuronal cells following neural injury. OBJECT REPRESENTATIONS
IN CORTEX: DYNAMIC AND LONG-TERM
PL4 LESLIE G. UNGERLEIDER
of Brain and Cognition,
National Institute of Mental Health, Bethesda, MD USA.
Physiological studies in monkeys have demonstrated that plastic neuronal changes are induced in the cortex during the storage and retrieval of object representations. In memory demanding tasks, such as delayed matching-to-sample, three commonly observed neuronal mechanisms are repetition suppression, enhancement, and delay activity. In repetition suppression, repeated experience with the same visual object leads to reduced responses of visual neurons. Repetition suppression appears to be an automatic mechanism that is an intrinsic property of visual cortical areas, such as the inferior temporal cortex. In contrast to repetition suppression, in neuronal enhancement, the responses of visual neurons are increased for visual stimuli that have behavioral relevance. Delay activity is found in tasks in which monkeys are required to actively hold specific information “on line” for short periods of time. Both enhancement and delay activity are not considered to be automatic mechanisms intrinsic to the inferior temporal cortex. Instead, these dynamic changes in the responses of visual neurons appear to reflect the effects of voluntary processes, perhaps mediated by feedback inputs from prefrontal cortex. Evidence from functional brain imaging studies in humans indicates that repetition suppression is important for priming, a type of implicit memory, whereas enhancement and delay activity contribute to explicit memory retrieval and working memory, respectively.
OF GLlAL CELL PROLIFERATION
MOSES V. CHAO, DONNA OSTERHOUT, Skirball Institute, New York University
RAVI TIKOO, PATRIZIA CASACCIA-BONNEFIL
Medical Center, New York, New York 10016
Oligodendrocytes, in addition to myelinating multiple axons in the central nervous system, possess a number of critical properties, such as the ability to provide trophic support, cluster Na + channels and produce inhibitory proteins that block As such, the number of oligodendrocytes generated during development must be under regeneration after nerve injury. Specific mechanisms by which oligodendrocytes progress from a proliferating precursor cell to a fully careful regulation. myelinating cell include the actions of two different regulatory molecules, the cell cycle inhibitor protein, p27”“‘, and the Fyn These two proteins are activated at or near the onset of oligodendrocyte tyrosine kinase, a Src family member. We have discovered that the levels of the cell cycle inhibitor protein, ~27~‘~, is increased in cortical differentiation. The binding of p27 to cyclin EiCDK2 complexes interferes oligodendrocyte progenitor cells undergoing differentiation. Also, Fyn tyrosine kinase activity is upregulated very early during oligodendrocyte progenitor with cell cycle progression. Concomitant with this increase is the appearance of several tyrosine phosphorylated proteins. The cell differentiation. increase in tyrosine kinase activity is specific to Fyn, as other Src family members are not active in oligodendrocytes. These studies may eventually lead to the identification of signals required for oligodendrocytes to form an insulating myelin sheet around axons in the nerve.