Biomedical subjects

Wen-Jun Gao

Publications and source records attributed to Wen-Jun Gao.

8 recordsLinked to original sources

PubMed2025

The locus coeruleus influences behavior by coordinating effective integration of fear memories and sensory input.

An essential function of memory is to guide behavior for better survival and adaptation. While memory formation has been extensively studied, far less is understood about how memory retrieval influences behaviors. In the auditory Pavlovian threat conditioning paradigm using C57BL/6J mice, retrieving a conditioned threat memory is associated with spiking in two dorsomedial prefrontal cortex (dmPFC) neurons with transient (T-neurons) and sustained (S-neurons) patterns. We show here that T-neurons and S-neurons are two distinct neuronal populations with different neuronal and synaptic properties and mRNA profiles. S-neuron spiking matches freezing behavior and is required for freezing. This sustained activity in S-neurons requires auditory inputs and the release of norepinephrine (NE) in the dmPFC. The activation of the locus coeruleus (LC) is initiated by dmPFC T-neuron inputs, sustained by auditory inputs, and is required for the transition to freezing by enhancing S-neuron activity. Interestingly, LC activation precipitates a brief period during which nonconditioned cues also induce freezing. Our findings highlight the critical contribution of the LC/NE system in the transition from memory to behavior, which coordinates the effective integration of memory, sensory inputs and emotional state for optimal adaptation.

Animals↗

PubMed2006

Acute clozapine suppresses synchronized pyramidal synaptic network activity by increasing inhibition in the ferret prefrontal cortex.

Recent studies have indicated that impaired neural circuitry in the prefrontal cortex is a prominent feature of the neuropathology of schizophrenia. Clozapine is one of the most effective antipsychotic drugs used for this debilitating disease. Despite its effectiveness, the mechanism by which clozapine acts on prefrontal cortical circuitry remains poorly understood. In this study, in vitro multiple whole cell recordings were performed in slices of the ferret prefrontal cortex. Clozapine, which effectively inhibited the spontaneous synchronized network activities in the prefrontal neurons, achieved the suppressive effect by decreasing the recurrent excitation among pyramidal neurons and by enhancing the inhibitory inputs onto pyramidal cells through a likely network mechanism. Indeed, under the condition of disinhibition, the depressing effects were reversed and clozapine enhanced the recurrent excitation. These results suggest that the therapeutic actions of clozapine in alleviating the positive symptoms of schizophrenia are achieved, at least partially, through the readjustment of synaptic balance between the excitation and inhibition in the prefrontal cortical circuitry.

Action Potentials↗

PubMed2006

[Diagnosis and treatment of priapism due to neoplasma of penis].

OBJECTIVE: To improve the clinician's ability for emergency treatment of priapism. METHODS: Both cases received 2 mg to 8 mg of metaraminol injection at the root of cavernous body, and perfusion of heparinized saline at glans and root of cavernous body of the penis by contrecoup, but they had not good response to the above therapy. At last surgery was performed. RESULTS: Total penectomy was performed for both cases. One case was diagnosed of penile sarcoma, and another was metastatic transitional cell carcinoma. CONCLUSION: Priapism due to neoplasma is infrequent, it should not be misdiagnosed in case of emergency.

Erectile Dysfunction↗

PubMed2005

NMDA receptor-mediated epileptiform persistent activity requires calcium release from intracellular stores in prefrontal neurons.

Various normal and pathological forms of synchronized population activity are generated by recurrent excitation among pyramidal neurons in the neocortex. However, the intracellular signaling mechanisms underlying this activity remain poorly understood. In this study, we have examined the cellular properties of synchronized epileptiform activity in the prefrontal cortex with particular emphasis on a potential role of intracellular calcium stores. We find that the zero-magnesium-induced synchronized activity is blocked by inhibition of sarco-endoplasmic reticulum Ca(2+)-ATPases, phospholipase C (PLC), the inositol 1,4,5-trisphosphate (IP3) receptor, and the ryanodine receptor. This same activity is, however, not affected by application of metabotropic glutamatergic receptor (mGluR) agonists, nor by introduction of an mGluR antagonist. These results suggest that persistent synchronized activity in vitro is dependent upon calcium release from internal calcium stores through the activation of PLC-IP3 receptor pathway. Our findings also raise the possibility that intracellular calcium release may be involved in the generation of pathologic synchronized activity in epilepsy in vivo and in physiological forms of synchronized cortical activity.

Action Potentials↗

PubMed2004

Construction of exogenous multiple epitopes of helper T lymphocytes and DNA immunization of its chimeric plasmid with HBV pre-S2/S gene.

AIM: To design and construct an exogenous multiple epitope of helper T lymphocytes (HTL), and to evaluate its effect on anti-HBs response through DNA immunization. METHODS: Artificial HTL epitope, PADRE and four other HTL epitopes from different proteins were linked together using splicing by overlap extension to generate exogenous multiple epitopes of HTL, MTE5. pcMTE5 and pcHB were generated by cloning MTE5 and fragments of HBV pre-S2/S gene into mammalian expression plasmid pcDNA3. Four chimeric plasmids were constructed by cloning MTE5 into the region of pre-S2 gene (Bam HI), 5' terminal of S gene (HincII, Xba I) and 3' terminal of S gene (Acc I) of pcHB respectively. BALB/c mice were used in DNA immunization of the recombinant plasmids. Anti-HBs was detected using Abbott IMx AUSAB test kits. RESULTS: The sequences of MTE5 and the 6 constructs of recombinant plasmids were confirmed to be correct by DNA sequencing. The anti-HBs response of the co-inoculation of pcHB and pcMTE5 was much higher than that of the inoculation of pcHB only (136.7+/-69.1 mIU/mL vs 27.6+/-17.3 mIU/mL, P<0.01, t = -6.56). Among the 4 chimeric plasmids, only the plasmid in which MTE5 was inserted into the pre-S2 region had good anti-HBs response (57.54+/-7.68 mIU/mL), and had no significant difference compared with those of pcHB and the co-inoculation of pcHB and pcMTE5. CONCLUSION: Exogenous multiple epitopes of HTL had immune enhancement when they were co-inoculated with pre-S2/S gene or inoculated in the chimeric form at a proper site of pre-S2/S gene of HBV. It might suggest that it was possible to improve hepatitis B vaccine using exogenous multiple epitopes of HTL. The antibody responses were very low using DNA immunization in the study. Thus, the immune enhancement effect of exogenous multiple epitopes of HTL has to be confirmed and the effect on overcoming the drawback of the polymorphism of HLA II antigens should also be evaluated after these chimeric plasmids are expressed in mammalian cell lines.

Amino Acid Sequence↗

PubMed2004

Target-specific differences in somatodendritic morphology of layer V pyramidal neurons in rat motor cortex.

Dendritic geometry has been shown to be a critical determinant of information processing and neuronal computation. However, it is not known whether cortical projection neurons that target different subcortical nuclei have distinct dendritic morphologies. In this study, fast blue retrograde tracing in combination with intracellular Lucifer yellow injection and diaminobenzidine (DAB) photoconversion in fixed slices was used to study the morphological features of corticospinal, corticostriatal, and corticothalamic neurons in layer V of rat motor cortex. Marked differences in the distribution of soma, somal size, and dendritic profiles were found among the three groups of pyramidal neurons. Corticospinal neurons were large, were located in deep layer V, and had the most expansive dendritic fields. The apical dendrites of corticospinal pyramidal neurons were thick, spiny, and branched. In contrast, nearly all corticostriatal neurons were small cells located in superficial layer V. Their apical dendritic shafts were significantly more slender, though spiny like those of corticospinal neurons. Corticothalamic neurons, which were located in superficial layer V and in layer VI, had small or medium-sized soma, slender apical dendritic shafts, and dendrites that were largely spine free. This study indicates that, in layer V of rat motor cortex, each population of projection neurons has a unique somatodendritic morphology and suggests that distinct modes of cortical information processing are operative in corticospinal, corticostriatal, and corticothalamic neurons.

Animals↗

PubMed2003

Dopamine modulation of perisomatic and peridendritic inhibition in prefrontal cortex.

The computations underlying cognitive functions are performed by a diversity of interactions between interneurons and pyramidal neurons that are subject to modulatory influences. Here we have used paired whole-cell recording to study the influence of dopamine on local inhibitory circuits involving fast-spiking (FS) and non-FS cells, respectively. We found that dopamine depressed inhibitory transmission between FS interneurons and pyramidal neurons but enhanced inhibition between non-FS interneurons and pyramidal cells. FS inhibitory transmission exhibited properties associated with presynaptic action at D(1) receptors that were not evident in non-FS inhibitory connections. In addition, FS and non-FS interneurons differed morphologically, forming contacts on the perisomatic and peridendritic domains, respectively, of their pyramidal cell targets. These findings provide evidence for both a dual mode of inhibition in prefrontal circuitry and circuit-dependent modulation by dopamine.

Action Potentials↗

PubMed2003

Selective modulation of excitatory and inhibitory microcircuits by dopamine.

Dopamine plays an important role in the working memory functions of the prefrontal cortex, functions that are impacted in age-related memory decline, drug abuse, and a wide variety of disorders, including schizophrenia and Parkinson's disease. We have previously reported that dopamine depresses excitatory transmission between pyramidal neurons in the prefrontal cortex. Here, using paired recordings, we have investigated dopaminergic modulation of excitatory transmission from pyramidal neurons to fast-spiking (FS) interneurons. In contrast to its effect on recurrent excitation, dopamine was without effect on excitatory transmission to FS interneurons. However, dopamine has directly enhanced the excitability of the FS interneurons to the extent that even a single excitatory postsynaptic potential could initiate spiking with great temporal precision in some of them. These results indicate that dopamine's effects on excitatory transmission are target-specific and that the axon terminals of pyramidal neurons can be selectively regulated at the level of individual synapses. Thus, dopamine's net inhibitory effect on cortical function is remarkably constrained by the nature of the microcircuit elements on which it acts.

Animals↗