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Biomedical subjects

B M Li

Publications and source records attributed to B M Li.

At least 19 recordsLinked to original sources
PubMed2006

Adult-onset hypothyroidism impairs paired-pulse facilitation and long-term potentiation of the rat dorsal hippocampo-medial prefrontal cortex pathway in vivo.

Thyroid hormones are critical for the maturation and function of the central nervous system. Insufficiency of thyroid hormones in the adulthood causes a wide range of cognitive dysfunctions, including deficits in learning and memory. The present study investigated whether adult-onset hypothyroidism would alter synaptic functions in the dorsal hippocampo-medial prefrontal cortex (mPFC) pathway, a neural pathway important for learning and memory. Adult hypothyroidism was induced by oral administration of 1% (g/l) antithyroid acting drug 6-n-propyl-2-thiouracil (PTU) to adult male Sprague-Dawley rats for 4 weeks. Postsynaptic potentials (PSP) were recorded in the mPFC by stimulating the dorsal hippocampal CA1 region in vivo. Basal synaptic transmission was evaluated by comparing input-output relationships. Paired-pulse facilitation and long-term potentiation were recorded to examine short- and long-term synaptic plasticity. Adult-onset hypothyroidism did not change the basal synaptic transmission, but significantly reduced paired-pulse facilitation and long-term potentiation of PSP. These inhibitions can be restored by thyroid hormone replacement. The results suggest that such alterations in synaptic plasticity of the dorsal hippocampo-mPFC pathway might contribute to understanding basic mechanisms underlying learning and memory deficits associated with adult-onset hypothyroidism.

Animals↗
PubMed2006

Dorsal hippocampal administration of triiodothyronine enhances long-term memory for trace cued and delay contextual fear conditioning in rats.

Thyroid hormones play critical roles in brain maturation and cognitive functions. The present study investigated the role of thyroid hormone in emotional learning and memory using trace and delay contextual and cued fear conditioning tasks, respectively. Rats were administered triiodothyronine (T3) into the dorsal hippocampal area 10 min before training or immediately after training, and were scored for freezing behaviour in the same context and in a novel context with and without an auditory cue that had been paired previously with an aversive stimulus, a foot shock. Rats administered T3 before and after training both exhibited significantly increased long-term fear memory in the trace cued and the delay contextual fear conditioning procedures compared to their control groups. The T3-administered rats were not significantly different from their respective controls on the acquisition and short-term fear memory in the trace and delay fear conditioning tasks. No significant difference on long-term trace contextual and delay cued fear memory, respectively, was found. These results indicate that the observed T3-induced enhancement of long-term contextual and cued fear memory was specific to the hippocampus-dependent conditioning tasks. These findings are the first to demonstrate that infusion of T3 into the dorsal hippocampus can improve performance on an emotional memory task.

Animals↗
PubMed2001

Pallidal activity is involved in visuomotor association learning in monkeys.

In order to examine whether the basal ganglia are involved in arbitrary visuomotor association, we recorded neuronal activity in the internal segment of the globus pallidus (GPi) of monkeys during a conditional visuomotor learning task. Two monkeys were presented a cueing visual stimulus, and following a delay period required to push, pull or turn a manipulator according to the cue. GPi neurons showed changes in activity during the delay period when the animals performed the task on the basis of a familiar stimulus-response association. Those changes in delay activity were enhanced as the monkeys were learning a new visuomotor association. The enhancement of the changes was selective to a following response. These results suggest that the basal ganglia are involved in arbitrary visuomotor association, especially during the learning of new associations.

Animals↗
PubMed2001

[An exploration of animal behavior screen platform for novel gene function in central nervous system].

For the purpose of large-scale screening of novel gene functions in mammalian nervous system, we have developed an animal behavior-monitoring platform employing antisense-oligo technology. Twenty genes of different categories were chosen from a low abundant gene (c)DNA sub-library of rat brain. Antisense oligo-nucleotides of these genes were designed and synthesized according to the homologues of the genes in mouse for mouse behavior tests. These antisense oligos were injected into the lateral ventricles of mouse brain using a Hamilton micro-syringe, with saline and oligos of scramble sequences as controls. These mice were tested with the following behavior model paradigms: metabolism, open field behavior, tail flick latency, and step-down test. Out of the 20 genes tested, 14 genes showed significant behavioral differences from the control groups at the level of P value less than 0.05 or 0.001 in different behavior animal models.

Animals↗
PubMed2000

Deficit in conditional visuomotor learning by local infusion of bicuculline into the ventral prefrontal cortex in monkeys.

To explore the role of the ventral prefrontal cortex (PFv) in conditional visuomotor learning, we infused locally bicuculline, a GABAergic antagonist, into the PFv of two monkeys, well trained on a two-problem visuomotor task. The task required the monkeys to execute one of two motor actions (moving a handle to the left or to the right) in response to one of two familiar visual patterns (circle or triangle). The two patterns mapped 1:1 onto the two motor actions: for each pattern one and only one motor action was scored, correct and reinforced. In contrast to these sessions with familiar patterns, in the learning sessions the monkeys were presented with one or two novel patterns and required to learn the arbitrarily determined associations between these patterns and the two motor actions. We found that bilateral infusion of bicuculline into PFv dramatically impaired the monkeys' ability to learn novel pattern-response associations: the trials and errors to criterion (90% correct) increased significantly. The errors were mainly an inability to apply 'Win-Stay', 'Lose-Shift' and 'Change-Shift' strategies. There was no effect on the monkeys' performance in responding to familiar patterns. Similar infusion of bicuculline into the dorsal prefrontal cortex was without effect on either novel-pattern learning or familiar-pattern performance. We conclude that the ventral prefrontal cortex is necessary for learning new visuomotor associations, but has less importance, if any, for performing pre-established ones.

Animals↗
PubMed1999

Local infusion of an alpha-1 adrenergic agonist into the prefrontal cortex impairs spatial working memory performance in monkeys.

BACKGROUND: Stimulation of alpha-2 adrenoceptors in the monkey or rat prefrontal cortex (PFC) has been known to improve spatial working memory (SWM) and stimulation of alpha-1 adrenoceptors in the rat PFC has been reported to impair SWM. The present study attempted to replicate in monkey the rat experiments on alpha-1 adrenoceptor stimulation. METHODS: The alpha-1 adrenergic agonist phenylephrine or the alpha-2 adrenergic agonist guanfacine was infused into the dorsolateral prefrontal cortex (dlPFC) of monkeys performing the delayed-response (DR) task, a task of SWM, to see how the drugs affect SWM performance. RESULTS: Phenylephrine infusion in dlPFC significantly impaired DR performance, whereas guanfacine improved performance. The effects of both drugs were delay-dependent. Infusions outside dlPFC were ineffective. CONCLUSIONS: Stimulation of prefrontal cortical alpha-1 adrenoceptors impairs SWM function in monkeys, consistent with the parallel study in rats, whereas stimulation of alpha-2 adrenoceptors improves SWM, indicating that alpha-1 and alpha-2 adrenoceptors may have opposing roles in the PFC.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1999

Alpha-1 noradrenergic receptor stimulation impairs prefrontal cortical cognitive function.

BACKGROUND: Many neuropsychiatric disorders are associated with high levels of noradrenergic turnover, and most antipsychotic medications have alpha-1 adrenoceptor blocking properties, yet little is known about alpha-1 influences on higher cortical function. METHODS: The alpha-1 adrenergic agonist, phenylephrine, was infused into the prefrontal cortex (PFC) of rats (0.1 microgram/0.5 microL) performing a spatial working memory task, delayed alternation. The phenylephrine response was challenged with coinfusion of the alpha-1 adrenergic antagonist, uripidil (0.01 microgram), or with a dose of lithium chloride (4 mEq/kg, i.p., 18 hours) known to suppress phosphotidylinositol (PI) turnover, the second messenger pathway coupled to alpha-1 adrenoceptors. RESULTS: Phenylephrine infusions in PFC markedly impaired delayed alternation performance. The phenylephrine response was reversed by coinfusion of uripidil, or by pretreatment with lithium, consistent with actions at alpha-1 adrenoceptors coupled to a PI pathway. CONCLUSIONS: These findings demonstrate that alpha-1 adrenoceptor stimulation in the PFC impairs cognitive function. Excessive stimulation of alpha-1 adrenoceptors may contribute to PFC deficits (e.g., distractibility, impulsivity) in disorders such as mania, dementia, and anxiety associated with high noradrenergic turnover.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1999

Alpha-2 adrenergic modulation of prefrontal cortical neuronal activity related to spatial working memory in monkeys.

The effects of systemically administered or iontophoretically applied clonidine (alpha-2 adrenergic agonist) and iontophoretically applied yohimbine (alpha-2 adrenergic antagonist) were examined on prefrontal cortical (PFC) neurons related to spatial working memory (SWM). Systemically administered clonidine (0.04 mg/kg) enhanced SWM-related PFC neuronal activity by 32.5 +/- 14.5%, (mean +/- SD; n = 25 neurons). The facilitatory effect of clonidine was antagonized by iontophoretically applied yohimbine. Iontophoretically applied clonidine enhanced SWM-related PFC neuronal activity by 38.2 +/- 18.6%, (n = 13 neurons), whereas similarly applied yohimbine suppressed it by 34.4 +/- 17.8% (n = 28 neurons). These results indicate that: a) systemically administered clonidine can facilitate SWM-related PFC neuronal activity through actions at alpha-2 adrenoceptors in the PFC; and b) conversely, blockade by yohimbine of alpha-2 adrenoceptors in the PFC suppresses SWM-related neuronal activity. The present study provides neurophysiological evidence that alpha-2 adrenoceptors in the PFC are involved in the cellular mechanisms underlying working memory.

Action Potentials↗
PubMed1999

[Roles of alpha-2 adrenoceptor in prefrontal cortical cognitive functions].

Studies in non-human primates have demonstrated that norepinephrine can improve, through actions at postsynaptical alpha-2A adrenoceptors, cognitive functions of the prefrontal cortex, such as attentional regulation, working memory and response inhibition. Several psychiatric disorders, including attention-deficit hyperactivity disorder (ADHD), show prominent syndromes seen in cognitive deficits of the prefrontal cortex. These basic studies help develop novel pharmacotherapies for psychiatric disorders such as ADHD.

Adrenergic alpha-Agonists↗
PubMed1998

Alpha-2 adrenergic modulation of prefrontal cortical neuronal activity related to a visual discrimination task with GO and NO-GO performances in monkeys.

The effects of clonidine (a selective agonist for alpha-2 receptor) and B-HT920 (an agonist for both alpha-2 and D2 receptors) were examined iontophoretically on neurons in the prefrontal cortex of three monkeys performing a visual discrimination task with GO and NO-GO responses. A total of 212 task-related neurons were sampled, of which 120 neurons were related to the visual signals (visually-related neurons; 32 neurons were related to the warning signal, 45 to the GO signal and 43 to the NO-GO signal), 34 neurons were related to both the GO signal and GO response ('intermediate'-related neurons), and 58 neurons were related to GO response (movement-related neurons). Clonidine and B-HT920 were tested in 137 and 115 neurons, respectively, and showed mainly a facilitatory effect on the neurons. Clonidine enhanced the visually-related activity in 83.0% of modulated neurons, the intermediate-related activity in 81.0% neurons and the movement-related activity in 85.0% neurons. Similarly, B-HT920 enhanced the visually-related activity in 80.0% of modulated neurons, the intermediate-related activity in 77.8% neurons and the movement-related activity in 81.0% neurons. The facilitatory effect of clonidine or B-HT920 on the visually-related activity was stronger than that on the movement-related activity. In 22 visually-related neurons enhanced by clonidine and-or B-HT920 (6 WS-, 7 GS- and 9 NS-related neurons), the alpha-2 antagonist yohimbine suppressed the visually-related activities. In 13 neurons enhanced by B-HT920, the facilitatory effect of B-HT920 was blocked by yohimbine, but not by the D2 antagonist sulpiride. The present results suggest that alpha-2 adrenoceptors in the monkey prefrontal cortex are involved in neural processing related to visual discrimination and selection of GO and NO-GO responses, and that the facilitatory effect of B-HT920 may be mediated vis alpha-2 adrenoceptors instead of D2-receptors.

Adrenergic alpha-Agonists↗
PubMed1997

Epstein-Barr virus in synergy with tumor-promoter-induced malignant transformation of immortalized human epithelial cells.

It is difficult to study how Epstein-Barr virus (EBV) causes transformation of human epithelial cells. The major difficulty is that cultured human epithelial cells do not express EBV receptor (complement receptor 2, CR2), hence EBV cannot infect such epithelial cells directly. In order to investigate the role of EBV in the transformation of human epithelial cells, pSG-CR2-Hyg carrier was transfected into immortalized human epithelial cells (293 cells) to express EBV receptor. EBV could infect these CR2-positive cells directly, and expressed EBV antigens. EBV-infected epithelial cells grew in piles with multiple cellular layers and lost contact inhibition in vitro. In soft-agar culture containing 12-0-tetradecanoylphorbol 13-acetate (TPA), EBV-infected 293 cells formed more and larger colonies. When EBV-infected 293 cells were transplanted subcutaneously into nude mice, and treated with TPA, poorly differentiated carcinoma was induced. These results suggest that EBV could induce the malignant transformation of immortalized human epithelial cells in synergy with TPA.

Animals↗
PubMed1997

Dopaminergic modulation of neuronal activity in the monkey putamen through D1 and D2 receptors during a delayed Go/Nogo task.

Using multibarreled glass micropipettes, we recorded single-unit activity in the putamen, and iontopho retically applied D1 and D2 dopamine receptor agonists (SKF38393, quinpirole) and antagonists (SCH23390, sulpiride) while two monkeys were performing a delayed Go/Nogo task. The putaminal neurons exhibited changes in activity during various task periods (hold, cue, delay, response, and reward periods) in both Go and Nogo trials. Of 296 task-related putaminal neurons, 87 showed activity changes in Go trials only (Go type), 74 in Nogo trials only (Nogo type), 99 in both trials during the same task periods (Both type), and 36 in both trials but during different task periods (Different type). These 296 neurons were examined as regards the effects of both D1 and D2 agonists and/or antagonists, and 234 neurons responded to either D1 - or D2-related substances or both. Among them 41% of neurons responded to the D1 substances only (D1 group), 36% responded to the D2 substances only (D2 group), and 23% responded to both D1 and D2 substances (D1D2 group). During the iontophoretic application of the D1 and D2 substances, most of the responding neurons changed their task-related activity but not their baseline firing rates. The D1 agonist increased the activity in 19 neurons and decreased it in 105 neurons. On the other hand, the D2 agonist increased the activity in 54 neurons and decreased it in 50 neurons. The D1 and D2 substances modulated the activity in both Go and Nogo trials. Each of the three D1/D2 groups (D1, D2, and D1D2 groups) contained all four Go/Nogo types (Go, Nogo, Both, and Different types) of neurons. Percentages of each Go/Nogo type of neuron were comparable among the three D1/D2 groups. The D1 and D2 substances modulated the activity related to various task periods. Each of the three D1/D2 groups included neurons activated during the cue, delay, response, or reward period in Go and Nogo trials. Distributions of the neurons related to each task period were similar among the D1/D2 groups. These results suggest that dopamine can modulate the activity of single putaminal neurons through both D1 and D2 receptors and that the dopaminergic modulation through the two receptors in the putamen affects similar types of signals in behavioral control.

Animals↗
PubMed1997

[A microdialysis study of excitatory amino acid levels of the monkeys' caudate nucleus during the delayed go/no-go task].

Using in vivo microdialysis coupled with HPLC-fluorescent detection chemical analysis method, levels of excitatory amino acid were monitored in the caudate nucleus of rhesus monkeys (Macaca mulatta) during performance of a delayed go/no-go task in which movement or no-movement responses were executed depending on the position of a cue light. It was found that the levels of glutamate and aspartate in caudate microdialysates decreased by (31.68 +/- 3.85)% (n = 10, t9 = 6.51, P < 0.001) and (26.25 +/- 5.95)% (n = 10, t9 = 3.39, P < 0.01) respectively during the delayed go/no-go task performance as compared to their basal levels before the task performance. Glutamine and asparagine levels were also found decreased significantly (P < 0.05). In contrast, no such decreases were seen when the monkey performing a non-delayed go/no-go task or performing the task composed of delayed go-trials only. The results suggest that the excitatory amino acid transmission in the caudate nucleus may be involved in the delayed go/no-go task performance, and thereby provide a direct evidence for the modulation of motor working memory by glutamatergic transmission in caudate nucleus.

Animals↗
PubMed1994

Delayed-response deficit induced by local injection of the alpha 2-adrenergic antagonist yohimbine into the dorsolateral prefrontal cortex in young adult monkeys.

Two young adult monkeys (Macaca mullata) were trained to perform a delayed-response task that required the monkeys to remember a cued spatial position (left or right) over a delay interval and then to make a response to the cued position. Local injection of the alpha 2-adrenergic antagonist yohimbine (10 micrograms in 2 microliters saline) into the dorsolateral prefrontal cortex (Walker's area 46 and area 9) impaired the performance of the delayed-response task, and it was without effect on the performance of the task if there was no delay between the cue and choice signals. The main performing error after injection of yohimbine was that the monkeys responded to uncued position with higher rate. Local injection of the alpha 1-adrenergic antagonist prazosin (10 microgram in 2 microliters saline) or the beta-adrenergic antagonist propranolol (10 micrograms in 2 microliters saline) into the same cortical areas induced no significant effect on the performance of the task. The present study suggests that prefrontal alpha 2-adrenoceptors play an important role in the spatial working memory in young adult monkeys.

Animals↗
PubMed1994

[Prefrontal injection of the alpha 2-adrenergic antagonist yohimbine impairs performance of a delayed GO/NO-GO task in monkeys].

Two rhesus monkeys were trained to perform a delayed GO/NO-GO task, which was initiated by the monkey's pressing a lever. At 0.5 s after the lever-pressing, a white square (1.5 cm x 1.5 cm) was displayed on the right or the left of a computer screen and lasted 0.5 s as a cue. After a delay of 0.0-4.0 s, a red square (1.5 cm x 1.5 cm) appeared between the left-cue and right-cue positions as a signal for response choice. The monkey released the lever within 0.8 s if the cue had been on the right (GO trial), or kept on the lever-pressing for 1.2 s if the cue had been on the left (NO-GO trial). Short-term working memory during the delay was a non-spatially representational one. Local injection of the alpha 2-adrenergic antagonist yohimbine (10 micrograms) into the prefrontal cortex (Walker's areas 46, 9) contralateral to the performing hand decreased the correct rate of performance. The longer the delay period was, the more serious the impairment was. The performing error after injection of yohimbine was expressed mainly as "commissural" response (the monkey made GO response in NO-GO trial or NO-GO response in GO trial). Injection of the alpha 1-adrenergic antagonist prazosin (10 micrograms) or the beta-adrenergic antagonist propranolol (10 micrograms) did not impair the task-performance. Our results suggest that, prefrontal alpha 2-adrenoceptors may play an important role in the short-term working memory with non-spatial representation.

Animals↗
PubMed1993

GABAB modulation of neuronal activity related to visually guided movement in the monkey premotor cortex.

The effects of the gamma-aminobutyric acid-B (GABAB) receptor agonist baclofen and the GABAA receptor antagonist bicuculline methiodide on the activities of the same neurons in the premotor cortex of two monkeys while they performed a visually guided task with a GO or NO-GO response were investigated. While bicuculline methiodide induced excitatory responses in all of the task-related neurons examined, baclofen induced inhibitory responses in 75% of the examined neurons and excitatory responses in 25% of the neurons. The results indicate that, in the monkey premotor cortex, not only GABAA but also GABAB receptors are involved in GABAergic modulation of neuronal activities related to the visually guided behavioral performance.

Animals↗
PubMed1990

Multibarreled glass-coated tungsten microelectrode for both neuronal activity recording and iontophoresis in monkeys.

A multibarreled glass-coated tungsten microelectrode suitable for single-unit recording and iontophoresis in chronically behaving animals is described. The microelectrode was stiff enough to pass through the dura matter of behaving monkeys, and can be applied as a microiontophoretic electrode. The electrode is easy to build and usable in stabilized conditions after repeated penetrations.

Animals↗