Neurobehavioral Plasticity: Learning, Development, and Response to Brain Insults

By Linda P. Spear; Michael L. Woodruff et al. | Go to book overview

14
Neuronal Activity Regulates Nerve Growth Factor mRNA Expression in the Adult Rat Hippocampal Formation

Joe E. Springer Francis M. Sessler Hahnemann University School of Medicine

Byoung J. Gwag Washington University School of Medicine

Environmental, cellular, and molecular events all contribute to the plasticity of neuronal pathways in the developing and mature nervous system. The contribution of target-derived trophic factors in neuronal plasticity has been suggested and studied since the time of Cajal. In the last decade, several studies supported the role of nerve growth factor (NGF) as a target-derived trophic molecule for cholinergic neurons that innervate the hippocampal formation and neocortex ( Thoenen, Bandtlow, & Heumann, 1987; Whittemore & Seiger, 1987). NGF messenger RNA (mRNA) is localized primarily to the dentate granule cells of the hippocampal formation, and to a lesser degree in the pyramidal neurons of the hippocampus proper ( Ayer-Lelievre, Olson, Ebendal, Seiger, & Persson, 1988). These neurons are the synaptic targets of basal forebrain cholinergic cells that project primarily through the fimbria-fornix pathway ( Lewis & Shute, 1967; Swanson & Cowan, 1979). The trophic actions of NGF are initially mediated through blinding to a specific membrane-bound receptor. In the rat, NGF receptors are synthesized in basal forebrain cholinergic cell bodies and are transported to the hippocampal formation through the fimbria-fornix ( Holtzman et al., 1992; Johnson et al., 1987; Schwab, Otten, Agid, & Thoenen, 1979; Springer, Koh, Tayrien, & Loy, 1987; Springer, Robbins, Meyer, Baldino, & Lewis, 1990). Transection of the septo-hippocampal pathway results in the loss or dysfunction of cholinergic neurons in the medial septum and vertical limb of diagonal band, and these effects of transection can be reversed by exogenous NGF administration ( Hefti,

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