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Mol Neurobiol. 2019 Apr 18. doi: 10.1007/s12035-019-1588-0. [Epub ahead of print]

A New Neural Pathway from the Ventral Striatum to the Nucleus Basalis of Meynert with Functional Implication to Learning and Memory.

Author information

1
Pediatric Center, Zhujiang Hospital of the Southern Medical University, A- 3103, Building 39, No. 253 Gong-ye Road, Haizhu District, Guangzhou, 510280, Guangdong, China. shusiyun@126.com.
2
Department of Ear, Nose and Throat, Zhujiang Hospital of the Southern Medical University, Guangzhou, 510282, Guangdong, China.
3
Department of Neurosurgery, Fuzhou Central Hospital of Nanjing Military Region, Fuzhou, 350025, Fujian, China.
4
Department of Radiology, General Hospital of People's Liberation Army, Beijing, 100853, China.
5
Pediatric Center, Zhujiang Hospital of the Southern Medical University, A- 3103, Building 39, No. 253 Gong-ye Road, Haizhu District, Guangzhou, 510280, Guangdong, China.
6
Department of Neurology, Zhujiang Hospital of Southern Medical University, Guangzhou, 510282, Guangdong, China.
7
Emergency Department, Zhujiang Hospital of Southern Medical University, Guangzhou, 510282, Guangdong, China.
8
School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong.
9
Nanjing Junqu Hangzhou Sanatorium, 5 Long-jin Road, Hangzhou, 310007, China.
10
Anesthesia Department of Yue-Bei People Hospital, Shaoguan City, 512026, Guangdong, China.
11
The Fifth Affiliated Hospital of Southern Medical University, Guangzhou, 510900, China.
12
Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, 777 Glades Road, Boca Raton, FL, 33431, USA. jwu@health.fau.edu.

Abstract

The cholinergic neurons in the nucleus basalis of Meynert (NBM) are among the first group of neurons known to become degenerated in Alzheimer's disease, and thus the NBM is proposed to be involved in learning and memory. The marginal division (MrD) of the striatum is a newly discovered subdivision at the ventromedial border of the mammalian striatum and is considered to be one part of the ventral striatum involved in learning and memory. The present study provided evidence to support the hypothesis that the MrD and the NBM were structurally connected at cellular and subcellular levels with functional implications in learning and memory. First, when wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) was stereotaxically injected into the NBM, fusiform neurons in the MrD were retrogradely labeled with WGA-HRP gray-blue particles and some of them were double stained in brown color by AchE staining method. Thus, cholinergic neurons of the MrD were shown to project to the neurons in the NBM. Second, in anterograde tract-tracing experiments where WGA-HRP was injected to the MrD, the labeled WGA-HRP was found to be anterogradely transported in axons from the MrD to the synaptic terminals with dendrites, axons, and perikaryons of the cholinergic neurons in the NBM when observed under an electronic microscope, indicating reciprocal structural connections between the MrD and the NBM. Third, when bilateral lesions of the MrD were injured with kainic acid in rats, degenerative terminals were observed in synapses of the NBM by an electronic microscope and severe learning and memory deficiency was found in these rats by the Y-maze behavioral test. Our results suggest reciprocal cholinergic connections between the MrD of the ventral striatum and the NBM, and implicate a role of the MrD-NBM pathway in learning and memory. The efferent fibers of cholinergic neurons in the NBM mainly project to the cortex, and severe reduction of the cholinergic innervation in the cortex is the common feature of Alzheimer's patients. The newly discovered cholinergic neural pathway between the MrD of the ventral striatum and the NBM is supposed involved in the memory circuitries of the brain and probably might play a role in the pathogenesis of the Alzheimer's disease.

KEYWORDS:

Alzheimer’s disease; Electronic microscopy; Immunocytochemistry; Learning and memory; The nucleus basalis of Meynert (NBM); The striatum; Tract tracing; Y-maze

PMID:
31001802
DOI:
10.1007/s12035-019-1588-0

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