Synaptic Rearrangement in the Dentate Gyrus: Histochemical Evidence of Adjustments after Lesions in Immature and Adult Rats

Abstract

In immature animals, ablation of the entorhinal cortex elicited a rapid intensification of acetylcholinesterase (EC 3.1.1.7) staining in the outer one-quarter of the molecular layer of the dentate gyrus. Subsequent lesions of the septum eliminated this acetylcholinesterase intensification. Electron-microscopic histochemical analysis demonstrated a 30-fold increase in the number of acetylcholinesterase-positive synaptic endings in the intensification zone. The acetylcholinesterase augmentation thus appears attributable, in part at least, to an increase in the number of acetylcholinesterase-rich synaptic endings established by septo-hippocampal fibers. Observations in a comparative study -of immature and adult rats point to the animal's developmental state as a major determinant of differences in these lesion-induced neuronal adjustments.Both the anatomical and functional effects of brain injury are generally attributed solely to the loss of damaged or ablated neurons. Findings in recent experiments indicate that this view of the effects of brain lesions needs to be reexamined. Under some conditions, axons from intact neurons grow into areas vacated by the axons of damaged neurons and form new synapses that reoccupy the vacated synaptic territories (1-9).If such capacity for neural reorganization is a general property of brain tissue, these findings have several important implications for understanding the consequences of brain damage. First, in efforts to explain the physiological and behavioral effects of brain lesions it may become necessary to consider not only the net loss of neurons caused by the lesion, but also a possible secondary effect: the formation of new connections by intact neurons. Second, the reorganization of neuronal circuitry after brain damage could explain the frequently observed, but poorly understood, phenomenon of partial recovery of function after brain damage. Third, these findings have demonstrated that neuronal organization is much more dynamic than was heretofore realized; in fact, it has already been suggested that synaptic rearrangements are continuously taking place in the brain even under normal conditions (10). Thus, the induction of reactive synaptogenesis by a brain lesion provides a method of investigating what might well be one of the bases of functional plasticity in normal animals.We examined changes in the organization of the synapse population in the dentate gyrus of the rat's hippocampal formation after lesions that selectively destroy the massive Abbreviation: AChE, acetylcholinesterase. afferent system originating in the entorhinal cortex. In studies of synaptic reorganization, the dentate gyrus offers several advantages: (a) its normal synaptic organization is simple and well defined; (b) it is suitable for electrophysiological recording (11) so that the functional significance of any known structural changes eventually may be assessed; (c) the afferents of the dentate gyrus are accessible to experimental manipulation (e.g., surgical lesion); and (d) the syst...

Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment

“…31,57 This plasticity response is marked by sprouting of cholinergic innervation into hippocampal sites vacated by the loss of the ERC synaptic input. 55,56,58 This loss of input results in a disconnection of the hippocampus from ERC in AD. 59 -62 The source of the new compensatory response is the cholinergic projection neurons of the medial septal/diagonal band (MS/DB) complex; these neurons provide the major cholinergic innervation to the hippocampus.…”

Adeno-Associated Virus Vector Expressing Nerve Growth Factor Enhances Cholinergic Axonal Sprouting after Cortical Injury in Rats

“…Lynch et al, 1972) to label sprouting by the AChE-containing, cholinergic septodentate pathway (Fass and Ramirez, 1984). The AChE label is localized primarily to terminals and axons (Shute and Lewis, 1966;Cotman et al, 1973) and is taken as evidence of the AChE-containing septodentate pathway (Steward, 1992) (for review, see Ramirez, 2001). Lesion assessments were performed on tissue stained with cresyl violet acetate to determine the extent of injury in the vicinity of the injection site and to confirm that the electrolytic lesions were localized to the medial and lateral aspects of the entorhinal area.…”

Variants of olfactory memory and their dependencies on the hippocampal formation

“…Horizontal sections were taken from the last third of hippocampus and adjacent entorhinal cortex. Every fourth coronal section was stained for acetylcholinesterase, a histochemical procedure which allows determination ofthe extent of denervation in hippocampus produced by damage to the retrohippocampal area (Lynch et al, 1972;Cotman et al, 1973). Every fourth horizontal section was stained with cresyl violet to verify the extent of actual tissue loss in the area of lesion.…”