Altered functional connectivity of the marginal division in Parkinson's disease with mild cognitive impairment: A pilot resting-state fMRI study.

BACKGROUND: The marginal division (MrD) is an important subcortical center involved in learning and memory. Mild cognitive impairment (MCI) is commonly seen in patients with Parkinson's disease (PD), but the neurobiological basis is yet to be elucidated. PURPOSE: To use resting-state functional magnetic resonance imaging (rs-fMRI) to explore the altered functional connectivity (FC) of the MrD in patients with PD-MCI. STUDY TYPE: Prospective pilot study. POPULATION: Twenty-five patients with PD-MCI; 25 PD patients and no cognitive impairment (PD-NCI); and 25 healthy control (HC) participants. SEQUENCE: 3.0 T GE Healthcare MRI scanner; three-dimensional T1 -weighted fast spoiled gradient recalled echo (3D T1 -FSPGR); rs-fMRI. ASSESSMENT: The MrD was defined using manual delineation, which was the seed point to compute the FC to examine correlations between low-frequency fMRI signal fluctuations in MrD and the whole brain. STATISTICAL TESTS: Between-group comparisons of the rs-fMRI data were computed using two-sample t-tests in a voxelwise manner after controlling for age and sex, to determine the brain regions that showed significant differences in FC with the bilateral MrDs. Correlation analyses were performed for FC values and cognitive abilities in patients with PD. RESULTS: In the PD-MCI group, compared with the PD-NCI group, we observed lesser FC between the MrD bilaterally and right putamen, left insula, left cerebellum, and left thalamus; greater FC between the MrD bilaterally and left middle cingulate cortex, left middle frontal gyrus, left superior frontal gyrus, left supplementary motor area, and left middle/inferior occipital gyrus. Moreover, the strength of FC between the MrD and regions that showed differences between the PD-MCI and PD-NCI groups was significantly correlated with neuropsychological scores in patients with PD. DATA CONCLUSION: The current study suggests that MrD dysfunction may contribute to MCI in PD. However, the mechanisms underlying this process require further investigation. Level of Evidence 1. Technical Efficacy Stage 2. J. Magn. Reson. Imaging 2019;50:183-192.

Different memory patterns of digits: a functional MRI study.

BACKGROUND: Psychological investigations and functional imaging technology have been used to describe neural correlations of different types of memory with various stimuli. Memory with limited storage capacity and a short retention time can be classified as short-term memory (STM) while long-term memory (LTM) can be life-long without defined capacity. METHODS: To identify brain activation pattern associated with different modes of memory for numerical figures, we detected brain activities from twenty-two healthy subjects when performing three types of memory tasks for numbers, namely STM, LTM and working memory (WM), by using functional magnetic resonance imaging (fMRI) technique. RESULTS: The result revealed variable patterns of activation in different brain regions responding to different types of memory tasks. The activation regions with primary processing and transient maintenance of STM for numerical figures are located in the visual cortex and mainly encoded by visual representations, while LTM was encoded by semantics and mainly recruiting left frontal cortex. We also found that subcortical structures, such as the caudate nucleus and the marginal division of the striatum, plays important roles in working memory. CONCLUSIONS: Activation of different brain regions in these three kinds of memories, indicating that different kinds of memories rely on different neural correlates and mental processes.

Effect of normal aging on the structure of marginal division of neostriatum as measured by MR phase imaging and diffusion tensor imaging.

PURPOSE: To investigate the structural changes of marginal division (MrD) which is the high intensity zone between globus pallidus and putamen on phase image in the human brain. MATERIALS AND METHODS: The structural changes of MrD were investigated based on MR phase imaging and diffusion tensor imaging (DTI) data at 3.0 Tesla (T) MR scanner in 72 volunteers. Phase value, including high iron components (HIC), low iron components (LIC), LIC ratio, and average iron components (AIC), were obtained using histogram analysis about the head of caudate nucleus (CA), globus pallidus (GP), putamen (PU), and MrD. The structural measurement of MrD was applied on corrected phase images (CPIs). Average apparent diffusion coefficient (ADC) values and fractional anisotropy (FA) values were calculated based on DTI data. RESULTS: MrD showed negative correlation for LIC with aging, with the highest HIC (left/right 2149.3 ± 19.6/2155.9 ± 17.9) and LIC (left/right 1996.6 ± 18.2/1999.6 ± 20.7), the lowest LIC ratio (left/right 21.5% ± 7.9%/19.4% ± 8.0%), and the highest AIC (left/right 2116.4 ± 21.4/2124.7 ± 21.0). The width (Head: left/right 2.01 ± 0.41 mm/1.86 ± 0.36 mm; Body: left/right 1.84 ± 0.38 mm/1.49 ± 0.29 mm; Tail: left/right 1.17 ± 0.36 mm/1.05 ± 0.23 mm) and area (left/right 49.44 ± 9.71 mm2 /42.75 ± 8.80 mm2 ) of MrD showed negative correlation with aging, presenting gradually narrower pattern based on CPIs. Average ADC value (left/right 0.69 ± 0.04 10-3 mm2 /s / 0.71 ± 0.03 10-3 mm2 /s) revealed negative correlation, while FA value (left/right 0.19 ± 0.03/0.22 ± 0.03) revealed positive correlation with aging. CONCLUSION: The findings suggested that the structure measurements based on CPIs and DTI could provide a simple and effective tool for the evaluation of MrD in vivo in the human brain and for the assessment of the changes seen with aging. LEVEL OF EVIDENCE: 1 J. MAGN. RESON. IMAGING 2017;45:1343-1351.

Altered functional connectivity of the marginal division in migraine: a resting-state fMRI study.

BACKGROUND: The marginal division of neostriatum (MrD) is a flat, pan-shaped zone between the neostriatum and the globus pallidus, and previous documents demonstrated that it was involved in the modulation of pain. The aim of this study is to investigate the roles of the MrD of the human brain in the chronicization migraine using resting state functional magnetic resonance imaging (rs-fMRI). METHODS: Conventional MRI, 3D structure images, and rs-fMRI were performed in 18 patients with episodic migraines (EM), 16 patients with chronic migraine (CM), 44 patients with medication overuse headache plus chronic migraine (MOH + CM), and 32 normal controls (NC). MrD was defined using manual delineation on structural images, and was selected as the seed to calculate the functional connectivity (FC). RESULTS: Compared with the NC group, the decreased FC of MrD was observed in the EM and CM groups, and increased FC of MrD was demonstrated in all patient groups. Compared with the EM group, the decreased FC of MrD was revealed in the CM and MOH + CM groups, and the increased FC occurred only in the CM group. Increased FC of MrD alone was observed in the MOH + CM group compared with that in the CM group. CONCLUSION: This study confirmed the double neuromodulation network of MrD in pain modulation and migraine chronicization; however, the mechanism requires further investigation.

[A study on the neuronal mechanism of retrieval of long-term digital memory in human by functional magnetic resonance imaging].

To investigate the neuronal mechanism of retrieval of long-term digital memory in healthy volunteers, functional magnetic resonance imaging (fMRI) technique was used in the study. Twenty-two right-handed volunteers were subjected to a long-term digital memory test with block-design. The memory task and control task were adopted in the experiment alternatively. The fMRI data were recorded by a Siemens 1.5T MR machine and analyzed by SPM99. The activated brain regions were shown in the Talairach coordinate. The results showed that the Brodmann's area (BA) 9 region in left middle frontal gyrus was the most activated cortex during the long-term digital memory task. The left medial frontal gyrus, left inferior frontal gyrus, right inferior frontal gyrus, cingulate gyrus, left inferior parietal lobule, left superior parietal lobule, right superior parietal lobule, right middle temporal gyrus, left lingual gyrus, left middle occipital gyrus, right middle brain, cerebellum and right caudate nucleus tail were also involved. The activation in cortices showed obvious left predominance. It is suggested that a series of brain regions with left predominance are involved in long-term digital memory. Left lateral frontal cortex would be the most important structure for information extraction, while the other cortices and their connections may be important for processing and long-term storage of digital information.

[The brain mechanism of memory encoding and retrieval: a review on the fMRI studies].

Memory encoding and memory retrieval are two important processes of the memory. The main results of studies on the neural basis of the memory encoding and memory retrieval by functional magnetic resonance image (fMRI) technique were summarized in this review. The neural basis of memory encoding and retrieval phases varies with different materials, memory types, and age stages. It means that the neural networks of these memory activities are separate. The functional locations of the activated brain areas during memory encoding and during memory retrieval phases are overlapped with distinction. The activated brain areas of memory encoding mainly locate in the prefrontal lobe, the temporal lobe, the parietal lobe, the anterior hippocampus, the thalamus, and the basal ganglia (including the striatum and the marginal division of the striatum). The activated brain areas of memory retrieval mainly locate in the prefrontal lobe, the temporal lobe, the entorhinal cortex, the perirhinal cortex, the posterior hippocampus, the thalamus, and the basal ganglia. The anterior hippocampus is mainly activated during the encoding phase, whereas posterior hippocampus is mainly activated during the retrieval phase. The intensity of the activated cerebral cortex regions during the encoding phase is stronger than that during the retrieval phase, whereas the opposite activated pattern is found in the subcortical structures, mainly the basal ganglia and thalamus, during the two phases. It seems that the stimulation might activate certain cerebral cortex areas during the memory encoding phase, then the information is transported to the subcortical structures and comes back to the cerebral cortex to complete the memory retrieval phase. The encoding and retrieval phases of the memory are supposed to be accomplished by a neural circuit among the cerebral cortex, basal ganglia, thalamus and cerebral cortex, rather than the cerebral cortex only.

[Activated brain areas during simple and complex mental calculation--a functional MRI study].

Functional magnetic resonance imaging (fMRI) was used to study the activated brain areas of human during simple and complex digital calculation, and to investigate the role of cortical and subcortical structures involved in the mental calculation. Sixteen right-handed healthy volunteers performed mental calculation of simple and complex addition/subtraction respectively, while the fMRI data were recorded by a Seimens 1.5 T MR machine. Block-design was used in the tasks. Two calculation tasks and one base-line tasks were performed for the block-design. Simple calculation task was single-digit addition and subtraction, while the complex was multi-digit addition and subtraction. The base-line task was to tell whether the two numbers were the same in every trial. Statistical parametric mapping (SPM99) was employed to process data and localize functional areas. We compared the average activation intensity of each activated brain regions in the same calculation task and the activation intensity of the same regions in both tasks respectively. Both the cortex and the subcortical structures including basal ganglia and thalamus were activated during simple and complex mental calculations. Similar brain regions in subjects including frontal lobe, parietal lobe, occipital lobe, cingulate gyrus, thalamus and cerebellum were engaged in simple and complex addition/subtraction. In the same task, activation intensity of all activated brain areas differed insignificantly. Compared with the complex task, the right parietal lobe was not activated in the simple one. The subcortical structures such as the caudate nucleus and the left marginal division of the striatum (MrD) were activated in both two calculation tasks. The cortical regions involved in both simple and complex addition/subtraction were similar. In conclusion, both the cortex and the subcortical structures were activated during the mental calculation. The cortex including the frontal cortex, parietal cortex, and cingulate gyrus were activated during mental calculation, while the subcortical structures such as the caudate nucleus, the globus pallidum and the left marginal division of the striatum also played a critical role in the neural networks of the calculation at the same time. Right parietal lobe (supramarginal gyrus) was engaged only in the complex task, which suggested that this region might be involved in the visuospatial memory and processing.

Endothelial nitric oxide synthase is expressed in amacrine cells of developing human retinas.

PURPOSE: To examine the expression and cellular distribution pattern of endothelial nitric oxide synthase (eNOS) in the developing human retina and to compare its expression with that in rats. METHODS: Expression of eNOS was examined by immunohistochemistry in retinas of humans ranging from 8.5 to 28 weeks of gestation (WG) and of rats. RESULTS: In the developing human retina, eNOS expression was first detected in the proximal margin of the neuroblastic layer in the incipient fovea-surrounding area at 12 WG. At 17 to 28 WG, eNOS-immunoreactive cells were located in the innermost part of the inner nuclear layer and in the ganglion cell layer, expanding to both temporal and nasal retinas and the processes projecting into the inner plexiform layer. These eNOS-positive cells coexpressed syntaxin and glutamate decarboxylase, and are probably GABAergic amacrine cells. The onset of eNOS expression in developing amacrine cells, however, preceded the invasion of retinal vasculature, long before vascular function involving these cells can be expected, suggesting that eNOS has a role not only in vasoregulation but also in retinal development. From 20 WG on, eNOS was also detected in the photoreceptors adjacent to the fovea. eNOS expression in amacrine cells and photoreceptors was observed in the central-to-peripheral and temporal-to-nasal gradients. However, in the developing rat retina, eNOS was expressed exclusively in the vascular endothelial cells. CONCLUSIONS: The results support that eNOS plays a role, not only in the regulation of vascular function but also in the process of retinal development in humans.

Encoding and Recognition Processing of Chinese Characters: A Functional Magnetic Resonance Imaging Study.

This study aimed to investigate the conceptual memory processes that underlie encoding and recognition processing of Chinese characters. Healthy participants (n = 14) performed a semantic-relatedness paradigm using categorically related logogram pairs from four different categories (fruit, animal, tool, and clothing). During intentional encoding, subjects were instructed to make semantic judgments and select category-correlated features to bind and memorize logogram pairs. During recognition, subjects were asked to recognize the memorized items. The MATLAB software and spatial clustering analysis were used for image data processing. Compared with baseline, encoding mainly activated BA13, with significant effects in BA6/8/9/46/45/47, BA24, BA7/39/40, BA37/20, and BA18/19; meanwhile, recognition mainly activated BA6/8/9/10/13/45/46/47, BA31, BA7/40, and BA18/19. Compared with recognition, encoding activated BA18/19/37/20/36 with a peak activation area in BA18. Compared with encoding, recognition significantly activated BA7, BA31/32, and BA10. In conclusion, distributed networks of discrete cortical regions with distinct roles are active during semantic processing of logograms. The ventral occipitotemporal and inferior frontal regions display increased levels of encoding-related activity. The dorsal medial brain regions, including the superior frontal gyrus and occipitoparietal regions, are associated with recognition-related activity.

New learning and memory related pathways among the hippocampus, the amygdala and the ventromedial region of the striatum in rats.

BACKGROUND: The hippocampus, central amygdaloid nucleus and the ventromedial region (marginal division) of the striatum have been reported to be involved in the mechanism of learning and memory. This study aimed elucidating anatomical and functional connections among these brain areas during learning and memory. RESULTS: In the first part of this study, the c-Fos protein was used to explore functional connections among these structures. Chemical stimulation of either hippocampus or central amygdaloid nucleus results in dense expression of c-Fos protein in nuclei of neurons in the marginal division of the striatum, indicating that the hippocampus and the central amygdaloid nucleus might be functionally connected with the marginal division. In the second part of the study, the cholera toxin subunit B-horseradish peroxidase was injected into the central amygdaloid nucleus to observe anatomical connections among them. The retrogradely transported conjugated horseradish peroxidase was observed in neurons of both the marginal division and dorsal part of the hippocampus following the injection. Hence, neural fibers from both the marginal division and the hippocampus directly projected to the central amygdaloid nucleus. CONCLUSION: The results implicated potential new functional and structural pathways through these brain areas during the process of learning and memory. The pathways ran from ventromedial portion (the marginal division) of the striatum to the central amygdaloid nucleus and then to the hippocampus before going back to the marginal division of the striatum. Two smaller circuits were between the marginal division and the central amygdaloid nucleus, and between the central amygdaloid nucleus and the hippocampus. These connections have added new dimensions of neural networks of learning and memory, and might be involved in the pathogenesis of dementia and Alzheimer disease.

Expression of c-fos and c-jun proteins in the marginal division of the rat striatum during learning and memory training.

BACKGROUND: A new brain region, the marginal division (MrD), was discovered at the caudal margin of the neostriatum. The MrD was shown to be involved in learning and memory in the rat. The aim of this study was to investigate the expression of the immediate-early genes c-fos and c-jun in the MrD of the striatum during learning and memory processes in the rat, immunocytochemical and Western blot methods were used to examine Y-maze trained rats. METHODS: The rats were divided into three groups, namely the training, pseudotraining, and control groups. After Y-maze training, the expression of the immediate-early genes c-fos and c-jun in the MrD of the rats was investigated using immunocytochemical and Western blot methods. RESULTS: After one hour of Y-maze training, the expression of c-jun and c-fos proteins was significantly enhanced in the MrD; the c-jun protein, in particular, was more intensely expressed in this region than in other parts of the striatum. The expression of these two proteins in the training group was significantly higher than in the pseudotraining and control groups. In addition, positive expression was also found in the hippocampus, cingulum cortex, thalamus, and in other areas. Western blot disclosed two immunoreactive bands for the anti-c-fos antibody (47 kD and 54 kD) and two immunoreactive bands for the anti-c-jun antibody (39 kD and 54 kD). CONCLUSIONS: These results indicate that the immediate-early genes c-fos and c-jun participate in signal transduction during the learning and memory processes associated with Y-maze training in rats.

The marginal division of the striatum and hippocampus has different role and mechanism in learning and memory.

The memory function of the hippocampal formation (Hip) and the marginal division (MrD) of neostriatum was compared. Rats with bilateral lesions of the MrD either immediate or 24 h after training in Y-maze were found to have decrease in correct runs in both groups. However, animals with transected afferent and efferent nerve bundles to isolate the Hip immediately or 24 h after training in Y-maze were found to show a decrease in correct runs only in the group injured immediately after Y-maze training but not in the 24 h group suggesting that MrD is likely involved in the entire process of long-term memory consolidation whereas the Hip only contributes to memory in the early stage. In addition, animals treated with a NMDA receptor (NMDAR) blocker, e.g. MK-801, showed decreased correct runs in Y-maze test and in expression level of phosphorylated CREB (pCREB) in neurons of the MrD but not in the Hip. Furthermore, animals treated with okadaic acid (OA), a potent protein phosphatase 1 inhibitor, showed increased correct runs in the Y-maze test. The expression level of pCREB and c-Fos and c-Jun was found increased in neurons of the MrD and the Hip in response to OA treatment. In conclusion, NMDAR and pCREB are involved in memory functions of both the Hip and the MrD. NMDAR might regulate pCREB level in neurons of the MrD but not in the Hip. Hence, the processes and mechanism of learning and memory involved in the MrD and the Hip may be different.

[Research progress in the structure and functions of the marginal division in the striatum].

In the year 1987, we discovered a new area in the striatum that was subsequently designated as the marginal division according to the location where it situates. More than 10 years of systemic study has yielded substantial knowledge of the unique structure of this new region, and it has come to light that the marginal division is predominantly associated with learning and memory functions, as have been recognized by researchers either nation-wide or world-wide. Further study of the marginal division may have potential significance in efforts to promote human intelligence and in contriving means for prevention of Alzheimer's disease.

Differential display analysis of gene expression in the hippocampus, marginal division and other related brain areas: a preliminary study.

OBJECTIVE: To investigate the difference in the expression profiles in the hippocampus, marginal division and other related brain areas for identification of genes specific to the hippocampus and marginal division. METHODS: Fetal hippocampus, marginal division, caudate putamen and amygdala were obtained and mRNA differential display technique was employed to study the gene expression in the 4 brain areas. RESULTS: Two differentially expressed fragments were isolated from each of the hippocampus and marginal division, and cloning and sequence analysis of one of the fragment 277 bp in length from the hippocampus showed total homology with the sequence of human clone AC0049. CONCLUSION: The 4 brain areas have different gene expression profiles.

[Expression of gamma-amino butyric acid and its receptor in the marginal division of rat striatum].

OBJECTIVE: To investigate the expression of the inhibitory amino acid gamma-aminobutyric acid (GABA) and its receptor GABAR (B1) mRNA in the marginal division of rat striatum. METHODS: The expression of GABA and its receptor GABAR (B1) mRNA was studied by way of immunocytochemistry and molecular in situ hybridization method. RESULTS: Dense GABA-positive immunoreactive fibers and a few positive cells were found in the marginal division of the rat striatum, along with glutamic acid decarboxylase (GAD)-positive fibers and cell bodies. GABA- and GAD-positive cells and fibers were also seen in the cerebral cortex and hippocampus. Numerous cells positive of the expression of GABAR (B1) receptors mRNA were observed in the marginal division whereas only a few positive cells were found in the caudate putamen. GABAR (B1) receptor mRNA expression was also observed in some cells in the cerebral cortex and hippocampus. CONCLUSION: The expression of GABA and its receptor in the marginal division of rat striatum indicates a regulatory mechanism of the marginal division of the striatum by GABA, suggesting that GABA can affect the learning and memory function of the marginal division through inhibiting the neurotransmitter release in the presynaptic terminal or modulating the other neurotransmitters.

[Functional connection between the marginal division and hippocampus in rats].

OBJECTIVE: To investigate the functional connection between the marginal division of the striatum and hippocampus, a brain region that play a vital role in learning and memory. METHODS: Morphological localization of functional activity of the nervous system was employed. Kainic acid (0.01%) was stereotaxically injected into the hippocampus as a chemical stimulus, and immunohistochemistry method was used to show the expression of c-Fos in rat brain. RESULTS: c-Fos was intensely expressed in the hippocampus, amygdaloid nucleus, the bed nucleus of the stria terminals and cerebral cortex; in the striatum, a stretch in the marginal division where c-Fos-positive nuclei congregated was observed, while c-Fos expression was scarcely detectable in the caudate putamen and globus pallidus. CONCLUSION: Functional connection exists between the marginal division and hippocampus in rats.

[Distribution of substance P and its receptor in the marginal division of rat striatum and its association with the function of learning and memory].

OBJECTIVE: To investigate the distribution of the substance P (SP) and its receptor in the marginal division (MrD) of rat striatum and to understand the relationship between SP and the learning and memory function of rats. METHODS: Using immunohistochemistry and in situ hybridization techniques, the distribution of SP and its receptor in the MrD was studied, and the relationship between the SP and learning and memory of the MrD was observed by means of SP receptor gene knockout in combination with Y-maze test. RESULTS: Numerous SP immunopositive fibers and large quantities of SP receptor protein and NK1 mRNA were identified in the MrD of rat striatum. After knockout of the SP receptor gene in the MrD, the ability of learning and memory of the rats was obviously decreased. CONCLUSION: SP and its receptor in the MrD may play important roles in the learning and memory function of rat, possibly through the regulation of the neurotransmitters as 5-HT by SP via NK1 receptor.

[Effects of kainic acid that damages the marginal division of rat striatum on hippocampal long-term potentiation].

OBJECTIVE: To investigate the relationship between the marginal division (MrD) of the striatum and other brain regions associated with learning and memory. METHODS: Long-term potentiation (LTP) was induced by high-frequency stimulation of the perforant path-dentate gyrus, and changes in hippocampal LTP after destruction of the marginal division with kainic acid were observed. RESULTS: High-frequency stimulation of the perforant path produced significant increases in the peak amplitudes of the population spike (PS) in normal rats and those receiving saline treatment. In rats with damaged MrD, the increase in PS and the excitatory postsynaptic potential were less obvious compared with normal or saline-treated rats, indicating that the LTP of the hippocampus was attenuated by damage of the MrD. CONCLUSION: Damage of the MrD impacts the LTP formation in the hippocampus.

[Expression of immediate-early genes c-fos and c-jun in the marginal division of striatum during learning and memory].

OBJECTIVE: To study the expression of immediate-early genes c-fos and c-jun in the marginal division (MrD) of rat striatum during learning and memory. METHODS: After Y-maze training in rats, the expression of immediate-early genes c-fos and c-jun in the MrD was investigated immunocytochemically. RESULTS: After 1 h of Y- maze training, the expression of c-Fos and c-Jun proteins was significantly enhanced in the MrD, where c-Jun protein in particular was more intensely expressed than in other parts of the striatum. The training group showed significantly higher expressions of the 2 proteins than pseudotraining group (P<0.01). In addition, positive expression was also observed in the hippocampus, cingulum cortex and other parts of the brain. CONCLUSION: Immediate-early genes c-fos and c-jun in the MrD participate in the signal transduction during learning and memory processes in the courses of Y-maze training of the rats.

[Effects of hypoxia on AChE and NADPH-d levels in the marginal division and learning and memory functions of rats].

OBJECTIVE: To observe the pathological changes and changes in acetylcholinesterase (AChE) and reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) levels in the marginal division (MrD) following hypoxia, and explore the relation of hypoxia to damages of learning and memory functions. METHODS: Hypoxia models were established in 40 SD rats by treatment with the mixture of 8% oxygen and 92% nitrogen 5 times daily for 5 consecutive days, and the sham-hypoxia group was constituted by 10 rats receiving normal oxygen supply in the same manner as above. Another 10 untreated rats were used as normal control. The rats completing the hypoxia induction procedures were subjected to Y-maze test before their brain sections, along with those of the rats in the other 2 groups, were prepared for HE staining and immunohistochemical staining. RESULTS: AChE immunohistochemical results of the normal control group revealed numerous AChE-positive fibers and some positive cells in the striatum where the MrD was more lightly stained than the other regions. In the rats with hypoxia, however, the MrD was more intensely stained in comparison with the control, but the stain in other regions of the striatum did not manifest any significant differences between the groups. The MrD of normal rats possessed more NADPH-d-positive cells, all spindle-shaped, than the other regions of the striatum, and hypoxia did not result in morphological changes of the cells but significant reduction of their quantity occurred. CONCLUSION: Hypoxia may cause reduction of the learning and memory functions of rats and gives rise to alterations of AChE and NADPH-d staining patterns in the MrD. The MrD is more vulnerable to hypoxia as evidenced by more obvious changes in AChE and NADPH-d staining in the MrD than in the other regions of the striatum, which may be associated with the impairment of the learning and memory functions by hypoxia.