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J N Davis

Publications and source records attributed to J N Davis.

At least 91 records · Page 5Linked to original sources

Facilitated reversal learning of a spatial-memory task by medial septal injections of 6-hydroxydopamine.

To assess the role of hippocampal norepinephrine in learning and memory, rats were treated with medial septal injections of 6-hydroxydopamine either prior to or after acquisition of a spatial-memory task. No effect on acquisition learning or retention was observed. However, reversal learning was significantly enhanced in all treated animals regardless of whether treatment was prior to or after acquisition. Our results do not support a role of hippocampal norepinephrine in selective attention, but rather indicate a direct involvement in memory processes.

Animals↗

Cholinergic denervation of the hippocampal formation does not produce long-term changes in glucose metabolism.

Decreased glucose metabolism is found in Alzheimer's disease associated with a loss of cholinergic neurons. The relationship between the chronic cholinergic denervation produced by medial septal lesions and glucose metabolism was studied using 2-deoxy-D-[3H]glucose in the rat hippocampal formation. Hippocampal glucose metabolism was increased 1 week after medial septal lesions. Three weeks after lesions, glucose metabolism was profoundly suppressed in all regions. By 3 months, intraregional hippocampal glucose metabolism had returned to control values. Our results demonstrate that chronic cholinergic denervation of the hippocampal formation does not result in permanent alterations of metabolic activity.

Acetylcholine↗

Regulation of hippocampal sympathetic ingrowth: role of afferent input.

Peripheral noradrenergic fibers from the superior cervical ganglion (SCG) appear in the hippocampal formation of the adult rat central nervous system following damage to the medial septal nucleus or its afferent fibers. The appearance of these fibers coincides with a significant and substantial increase in the concentration of norepinephrine in the dentate gyrus and in the ability of synaptosomes made from the dentate to take up [3H]norepinephrine (NE) in vitro. Up to 7 weeks following a medial septal lesion, dentate norepinephrine levels are significantly lower if the sympathetic preganglionic trunk has been sectioned at the time septal lesions are made. By contrast, the uptake of [3H]NE into dentate synaptosomes is not affected by the preganglionic section. Furthermore, if the sectioned preganglionic trunk is allowed to reinnervate the SCG, the dentate NE concentration rapidly returns to levels equivalent to dentates with intact sympathetic preganglionic trunks. In addition to the ingrowth of the sympathetic fibers, central noradrenergic fibers display a sprouting or 'pruning' response to medial septal lesions. These data show that afferent input regulates the neurotransmitter concentration during sympathetic ingrowth while retrograde influences from the target appear to regulate the density or extent of the growing fibers. The experimental findings are discussed in light of the hypothesis that the hippocampal formation is capable of producing a sympathetic growth factor following septal denervation.

Afferent Pathways↗

Acetylcholinesterase neurons in the lateral hypothalamus project to the spinal cord.

The possibility that cholinergic neurons of the basal forebrain project to the spinal cord was investigated utilizing the retrograde transport of bisbenzimide and [3H]choline as well as acetylcholinesterase histochemistry. A striking similarity was observed in the distributions of lateral hypothalamic neurons labeled with bisbenzimide and acetylcholinesterase. Only a small number of these neurons contained both markers, suggesting the possibility of a small cholinergic projection from the lateral hypothalamus to the spinal cord. The use of [3H]choline to test this hypothesis yielded negative results. Thus the present observations indicating that lateral hypothalamic neurons are cholinoceptive, are consistent with choline acetylcholinesterase immunohistochemical studies. The potential for basal forebrain cholinergic neurons to influence spinal autonomic activity via the lateral hypothalamus is discussed.

Acetylcholinesterase↗

Sprouting of noradrenergic fibers in hippocampus after medial septal lesions: contributions of the central and peripheral nervous systems.

The neuronal sprouting of noradrenergic fibers was studied in the hippocampal formation. The extent and time course of lesion-induced plasticity of both central and peripheral noradrenergic neurons was determined by assaying norepinephrine (NE) concentrations and high-affinity [3H]NE uptake in the dentate gyrus at 2 to 16 weeks after medial septal lesions. Two weeks after a medial septal lesion there was a dramatic decrease in dentate NE. During the subsequent weeks normal concentrations of dentate NE were reestablished. The recovery or increase of NE with time reflected a contribution from both central and peripheral noradrenergic systems. Although both central and peripheral noradrenergic systems contributed to this recovery, they did so in very different ways. The time course of the central noradrenergic response was slower than that of the peripheral system and the final NE concentrations were quite different for the two systems. The central adrenergic system's sprouting response apparently stabilized when normal NE concentrations were attained, whereas the ingrowth of peripheral sympathetic fibers continued to concentrations that were well above normal unoperated levels. The findings have implications in relationship to the different possible controlling mechanisms governing neuronal plasticity of the central and peripheral noradrenergic systems.

Animals↗

Topography of locus ceruleus neurons projecting to the area dentata.

The distribution of locus ceruleus neurons projecting to the dorsal and ventral area dentata was studied using the retrograde transport of horseradish peroxidase (HRP). Furthermore, the possibility that collaterals of single locus ceruleus neurons innervate both the dorsal and ventral area dentata was explored with a retrograde double-label technique using HRP and the fluorescent dye 4',6-diamidino-2-phenylindole 2 HCl (DAPI). Fusiform and multipolar neurons of the pars dorsalis of the locus ceruleus (LCd) were labeled after injection of HRP into the area dentata. The HRP-positive cells were found almost exclusively in the dorsal LCd after dorsal area dentata injections whereas ventral injections labeled neurons throughout the LCd. The highest density of LCd neurons labeled from the ventral area dentata was observed in the dorsal half of the LCd and thus overlapped with the distribution of neurons labeled from dorsal injections. Neurons containing both HRP and DAPI were observed in the dorsal LCd suggesting that the topographic coincidence of neurons labeled from dorsal and ventral area dentata was in part a result of single neurons having terminals in both loci.

Animals↗

Sympathetic sprouting and recovery of a spatial behavior.

After lesions of the medial septum, peripheral sympathetic fibers from the superior cervical ganglion appear in the hippocampal formation. To assess the functional significance of this neuronal rearrangement, we analyzed behavior on a spatial/memory task sensitive to hippocampal dysfunction, the radial eight-arm maze. The procedure allowed evaluation of both working and reference memory. All rats were able to master the task. Half of the rats then underwent either medial septal lesions and ganglionectomy or sham neurosurgery and ganglionectomy, and the other half underwent medial septal lesions or sham neurosurgery followed by ganglionectomy after further behavioral testing. Medial septal lesions in both groups disrupted taks performance with recovery of performance occurring with time. However, the rate of recovery was significantly enhanced in rats which had septal lesions and ganglionectomies simultaneously. Removal of the ganglion after recovery produced no effects on maze performance. Our results suggest that sympathetic ingrowth retards recovery processes.

Animals↗

Sustained elevation of hippocampal cyclic 3'-5' adenosine monophosphate levels after medial septal lesions.

The cyclic 3'-5' adenosine monophosphate (cyclic AMP) content of the rat hippocampal formation doubles during the week following a medial septal lesion and remains elevated for at least 1 month, the longest time period studied. This elevation in cyclic AMP does not result from sympathetic ingrowth, as neither superior cervical ganglion stimulation nor ganglionectomy influences hippocampal cyclic AMP content after lesions. Interruption of the cholinergic septohippocampal pathway in the fornix did not elevate hippocampal cyclic AMP content. Further, treatment of septal-lesioned animals with oxotremorine or of normal animals with atropine did not influence hippocampal cyclic AMP content. Finally, neither locus ceruleus lesions nor treatment with propranolol affected hippocampal cyclic AMP content. We believe this to be the first report of a sustained elevation in hippocampal cyclic AMP content. Like other long-term events, it is likely to have profound effects on hippocampal function and represents a remarkable brain adaptation to remote injury.

Animals↗

Potassium release by alpha 2-adrenergic receptor stimulation of rat parotid acinar cells.

alpha-Adrenergic stimulation elicited a rapid release of K+ from dispersed parotid acinar cells in the presence of external Ca2+. A recent classification of alpha-adrenergic receptors proposed that alpha 1 receptors facilitate Ca2+ entry while alpha 2 receptors interact with adenylate cyclase. We tested this proposal by studying the ability of selective alpha-adrenergic antagonists to prevent epinephrine-induced release of K+ from parotid cells. The alpha 1 agents, WB 4101 and prazosin, were less potent than the alpha 2 antagonist yohimbine. These data suggest that alpha 2-adrenergic receptors in the parotid might facilitate the entry of Ca2+.

Adrenergic alpha-Agonists↗

Anterograde and transcellular transport of a fluorescent dye, bisbenzimide, in the rat visual system.

Fluorescent labeling was seen in rat brain after injections of 10 microliters of 10% bisbenzimide into the posterior chamber of the eye. Small and spindle shaped fluorescent nuclei were seen in the ipsilateral optic nerve, chiasm and contralateral optic tract, while larger apparently neuronal nuclei were seen in regions such as the lateral geniculate and superior colliculus where the retinal projection terminates. These experiments suggest that, like radioactive compounds, fluorescent dyes undergo anterograde and transcellular transport following large injections. Although limited by sensitivity and the large injection volumes required, this anterograde transport and transcellular transfer of bisbenzimide may be useful in identifying cell populations near the terminal projections of specific neuronal pathways.

Afferent Pathways↗

(-)-[3H]Dihydroalprenolol binding in subcellular fractions of rat cortex following noradrenergic denervation.

Two weeks after noradrenergic denervation, beta-adrenergic receptor binding increased in 2 of 3 crude fractions of rat cortical homogenates, while the relative distribution of binding was unchanged on continuous sucrose density gradients of the crude synaptosomal fraction. When rat glioma cells were fractionated by the same methods, a band of membranes with beta-adrenergic receptor binding sedimented at the same sucrose density as synaptosomes. Thus membrane receptors remained associated with synaptosomes even in the absence of noradrenergic nerve terminals suggesting that a portion of these receptors are either glial or associated with non-noradrenergic nerve terminals.

Alprenolol↗

Sympathetic noradrenergic sprouting in response to central cholinergic denervation; a histochemical study of neuronal sprouting in the rat hippocampal formation.

An unusual example of neuronal sprouting occurs in the rat brain. Several weeks after fimbrial transection or septal lesions, peripheral sympathetic fibers appear in the dentate and hippocampal gyri. We compared the distribution of normal cholinergic septohippocampal fibers and nerve terminals with the distribution of noradrenergic sympathetic (sympathohippocampal) fibers after septal lesions using anterograde transport of horseradish peroxidase and fluorescence histochemistry. In addition, we destroyed other afferents to the hippocampal formation and examined the effect of subtotal septal lesions on acetylcholinesterase staining and the distribution of sympathohippocampal fibers. The combined results of these experiments suggest that peripheral noradrenergic fibers sprout specifically in response to destruction of central cholinergic fibers after septal lesions. This appears to be the first model of neuronal sprouting in the central nervous system where one identified transmitter system (noradrenergic) sprouts only in response to, and perhaps to replace, another specific transmitter system (cholinergic).

Acetylcholinesterase↗

Sympathohippocampal sprouting is directed by a target tropic factor.

In order to determine what aspect of septohippocampal denervation elicits sympathetic sprouting, entorhinal lesions were made to first elicit intensification of acetylcholinesterase (AChE) staining in the dentate molecular layer. Transport of horseradish peroxidase (HRP) from the septum confirmed that the dense band of AChE staining reflects the presence of septohippicampal fibers. Animals receiving entorhinal lesions, followed 30 days later by septal lesions, demonstrated the same pattern of sympathetic sprouting as seen in animals without entorhinal lesions. These results suggest that sympathohippocampal sprouting is directed by a tropic factor released by the cholinergic-denervated hippocampal formation.

Acetylcholinesterase↗