Recovery of choline acetyltransferase and acetylcholinesterase activities in the ipsilateral hippocampus following unilateral, partial transection of the fimbria in rats

doi:10.1016/0006-8993(83)90921-6

Brain Research

Volume 277, Issue 1, 24 October 1983, Pages 169-174

https://doi.org/10.1016/0006-8993(83)90921-6 Get rights and content

Abstract

An initial decrement followed by a significant recovery of choline acetyltransferase and acetylcholinesterase activities in the ipsilateral hippocampus was observed in rats with unilateral, partial transection of the fimbria. Regeneration of hippocampal cholinergic terminals could account for the parallel return towards normal of both the enzyme activities. We suggest that the still intact fimbrial fibres, homologous to those severed, contribute to the observed recovery.

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Cited by (20)

The fimbria-fornix/cingular bundle pathways: A review of neurochemical and behavioural approaches using lesions and transplantation techniques
1997, Progress in Neurobiology
Extensive lesions of the fimbria-fornix pathways and the cingular bundle deprive the hippocampus of a substantial part of its cholinergic, noradrenergic and serotonergic afferents and, among several other behavioural alterations, induce lasting impairment of spatial learning and memory capabilities. After a brief presentation of the neuroanatomical organization of the hippocampus and the connections relevant to the topic of this article, studies which have contributed to characterize the neurochemical and behavioural aspects of the fimbria-fornix lesion “syndrome” with lesion techniques differing by the extent, the location or the specificity of the damage produced, are reviewed. Furthermore, several compensatory changes that may occur as a reaction to hippocampal denervation (sprouting, changes in receptor sensitivity and modifications of neurotransmitter turnover in spared fibres) are described and discussed in relation with their capacity (or incapacity) to foster recovery from the lesion-induced deficits. According to this background, experiments using intrahippocampal or “parahippocampal” grafts to substitute for missing cholinergic, noradrenergic or serotonergic afferents are considered according to whether the reported findings concern neurochemical and/or behavioural effects. Taken together, these experiments suggest that appropriately chosen fetal neurons (or other cells such as, for instance, genetically-modified fibroblasts) implanted into or close to the denervated hippocampus may substitute, at least partially, for missing hippocampal afferents with a neurochemical specificity that closely depends on the neurochemical identity of the grafted neurons. Thereby, such grafts are able not only to restore some functions as they can be detected locally, namely within the hippocampus, but also to attenuate some of the behavioural (and other types of) disturbances resulting from the lesions. In some respects, also these graft-induced behavioural effects might be considered as occurring with a neurochemically-defined specificity. Nevertheless, if a graft-induced recovery of neurochemical markers in the hippocampus seems to be a prerequisite for also behavioural recovery to be observed, this neurochemical recovery is neither the one and only condition for behavioural effects to be expressed, nor is it the one and only mechanism to account for the latter effects. © 1997 Elsevier Science Ltd. All Rights Reserved.
Lesions of supracallosal or infracallosal hippocampal pathways in the rat: Behavioral, neurochemical, and histochemical effects
1994, Behavioral and Neural Biology
Long-term behavioral and neurochemical effects of bilateral lesions to only the infracallosal component of the “so-called” septohippocampal pathways (cingular bundle, fimbria and fornix) have not been assessed. This experiment compared the behavioral, histochemical and neurochemical effects of supracallosal (SUPRA; cingular bundle) and infracallosal (INFRA; fimbria-fornix) hippocampal denervations in Long-Evans female rats. The rats were tested, over two periods (8–52 and 92–170 days postlesion), for open field locomotion, spontaneous alternation and radial-maze performance. Subsequently, histochemical or neurochemical determinations of cholinergic, serotonergic and noradrenergic hippocampal innervations were performed using acetylcholinesterasestaining, determination of high-affinity synaptosomal uptake of choline and serotonin, and measurement of hippocampal serotonin and noradrenaline concentrations by HPLC methods. Whatever behavioral test was considered, no significant effect was found in rats with SUPRA lesions, whereas rats with INFRA lesions were permanently impaired in all tests. Histochemical and neurochemical analyses showed hippocampal cholinergic as well as serotonergic markers to be substantially decreased in INFRA rats as compared to SHAM and SUPRA rats. The SUPRA rats exhibited a weak but significant reduction of both serotonergic and noradrenergic markers compared to SHAM and INFRA rats. These results suggest that lesions limited to the infracallosal pathway induce a hippocampal denervation sufficient to account for most of the behavioral, histochemical and neurochemical deficits classically reported following extensive lesions of the anterior hippocampal connections. Since the behavioral and neurochemical deficits were found to be lasting, it is suggested that bilateral infracallosal damage to the septohippocampal pathways might constitute an interesting paradigm of partial hippocampal deafferentation to investigate the effects of neural grafts or other treatments in an animal model of Alzheimer's disease.
Compensatory changes of in vivo acetylcholine and noradrenaline release in the hippocampus after partial deafferentation, as monitored by microdialysis
1993, Brain Research
Lesions of the fimbria-fornix pathways are known to induce a partial cholinergic and noradrenergic denervation of the hippocampal formation, which is followed by a slow and protracted collateral sprouting by the spared afferents. Using the intracerebral microdialysis technique, compensatory changes in extracellular levels of acetylcholine (ACh) and noradrenaline (NA) have been monitored over time in the partially denervated hippocampus of awake unrestrained rats subjected to an unilateral fimbria-fornix (FF) transection. One week after the lesion, baseline ACh output was reduced by 90% and 80% in the dorsal and ventral hippocampus, respectively, and it remained depressed still by 6 months after lesion. KCl-evoked and atropine-stimulated ACh efflux were equally reduced by 1 week after lesion, remained depressed at 3 months, but showed a significant recovery by 6 months post-lesion. Tissue choline acetyltransferase (ChAT) activity levels, initially reduced by 92% and 86%, in the dorsal and ventral hippocampus, respectively, recovered significantly by 3 months and remained unchanged at 6 months. Baseline NA output was significantly reduced (−80%) in the dorsal hippocampus by 1 week after the lesion and showed a partial recovery over time (to 50% of normal), whereas the ventral part was not significantly affected by the FF lesion. The significant FF lesion-induced reduction in KCl- or desipramine (DMI)-stimulated NA release observed in the dorsal hippocampus at 1 week after the lesion remained unchanged during the subsequent months. By contrast, in the ventral hippocampus, the initial 65–70% reduction in KCl- and DMI-stimulated NA release significantly recovered to normal levels within 3 months post-lesion. The NA tissue levels were significantly reduced by 4 weeks after lesion, in the dorsal hippocampus and did not show any significant recovery over time. In the ventral hippocampus, these levels were significantly reduced only at 4 weeks. Transmitter turnover, expressed as the ratio between dialysate levels and tissue ChAT or NA content, showed a 3-fold increase in the dorsal hippocampus at 4 weeks after lesion, but not at later time points. This indicates that the spared noradrenergic and cholinergic afferents respond to the partial denervation by a transient increase in transmitter turnover, evident as early as 4 weeks post-lesion in the region of maximal denervation. This was followed by a long-term increase in evoked transmitter release which may result from a slowly progressing compensatory sprouting of the spared afferents.
Behavioral and anatomical consequences of unilateral fornix lesions and the administration of nimodipine
1991, Brain Research
Male Wistar rats subjected to unilateral fimbria-fornix transection by mechanical knife cut or to sham operations were tested in a water maze and in an open field. Half the animals in each group were treated with either 0.06 mg/kg nimodipine or vehicle, administered i.p. for 7 days, beginning the day of surgery. Animals were sacrificed and brains were processed for acetylcholine esterase (AChE) histochemistry. In the water maze, lesioned rats showed a significant impairment relative to the sham-operated animals. Nimodipine treatment did not improve performance. There were no differences among the groups in the observed frequencies of the open field behaviors of locomotion, hole-poke, rearing and grooming. A significant reduction of AChE-positive cell bodies was found in the medial septal region on the side of the lesion. There were no differences in water maze performance among groups of rats treated with 0.0, 0.5, 1.0, or 5.0 mg/kg nimodipine for 7 days, beginning the day of fimbria-fornix transection, in an attempt to determine any dose-dependent effect of the drug.
In vivo acetylcholine release as measured by microdialysis is unaltered in the hippocampus of cognitively impaired aged rats with degenerative changes in the basal forebrain
1991, Brain Research
Acetylcholine (ACh) release was studied in awake, freely moving animals in vivo microdialysis in the hippocampus of young (3-month-old) and aged (24-month-old) female Sprague-Dawley rats. Two groups of aged rats were selected on basis of their spatial learning performance in the Morris water maze: non-impaired aged rats which performed as well as the young control animals, and impaired aged rats which learnt the task very poorly. Baseline ACh overflow (in the presence of 5 μM neostigmine) was1.9 ± 0.3 ±pmol/15min in the young animals and1.6 ± 0.4pmol/15min in both the impaired and the non-impaired aged rats; these levels did not differ from each other. Depolarization by KCl (100 mM) or muscarinic receptor blockade by atropine (3 μM) added to the perfusion fluid produced dramatic, 4–6-fold, increases in ACh overflow that was similar in magnitude in both the young and the aged impaired and non-impaired rats. Behavioral activation by either handling or electrical stimulation of the lateral habenula produced 2–3-fold increases in extracellular ACh-levels in the hippocampus similarly in all three groups. The results indicate that hippocampal ACh release is maintained in aged rats that exhibit severe spatial learning and memory impairments and that the septo-hippocampal cholinergic system retains its capacity to increase its ACh release in response to both K⁺-induced depolarization and behavioral activation in the aged rat. In the subsequent morphometric analysis the cholinergic neurons in the septal-diagonal band area showed the expected reduction in both number (−20–30%) and size (−8%) in the aged impaired animals. This suggests that the ageing septo-hippocampal cholinergic system can compensate functionally for ongoing degeneration or atrophic processes also in the most severely affected aged animals. The present data do not exclude, however, that the behaviorally impaired aged rats may exhibit functionally important deficits in other dynamic aspects of cholinergic neurotransmission, or in the functional properties of the septo-hippocampal neurons not picked up by the microdialysis method.
Effect of nerve growth factor on the lesioned septohippocampal cholinergic system of aged rats
1991, Brain Research
Nerve growth factor (NGF) was injected intraventricularly into aged (24 months) rats with unilateral lesions of the lateral fimbria. The activity of choline acetyltransferase (ChAT) was determined in the septum and hippocampus from the normal unlesioned rats, lesioned and cytochrome c-treated rats (controls), and lesioned and NGF-treated rats at different times after the lesion. NGF-injection for 15 days after the lesion resulted in an increase of the ChAT activity in both the contralateral hippocampus and the entire septum, to about 130% of that in the normal animals, but resulted in a slight increase in the ipsilateral lesioned hippocampus, when compared to the activity in the ipsilateral side of the cytochromec-treated controls. NGF-injection for 30 days after the lesion resulted in a 48% increase of the ChAT activity in the ipsilateral hippocampus as compared to cytochrome c-treated controls, but failed to result in a significant increase in the contralateral hippocampus. These findings indicate that atrophic cholinergic neurons in aged animals are similarly responsive to NGF treatment, like these in the young animals. Moreover, these findings suggest that the responses of basal forebrain cholinergic neurons to NGF treatment varies with time after the lesion and imply that the NGF administration can promote the collateral sprouting from spared cholinergic fibers after the lesion in the aged forebrain.

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Recovery of choline acetyltransferase and acetylcholinesterase activities in the ipsilateral hippocampus following unilateral, partial transection of the fimbria in rats

Abstract

Exp. Neurol.

Brain Research

Exp. Neurol.

Brain Research

Brain Research

Neuroscience

Regeneration of monoaminergic and cholinergic neurons in the mammalian central nervous system

Physiol. Rev.

Reactive synaptogenesis in the hippocampus

Synapse replacement in the nervous system of adult vertebrates

Physiol. Rev.

Radiochemical microassays for the determination of choline acetyltransferase and acetylcholinesterase activities

Biochem. J.