Analysis of temperature-dependent abnormal bursting patterns of neurons in Aplysia

Temperature affects the firing pattern and electrical activity of neurons in animals, eliciting diverse responses depending on neuronal cell type. However, the mechanisms underlying such diverse responses are not well understood. In the present study, we performed in vitro recording of abdominal ganglia cells of Aplysia juliana , and analyzed their burst firing patterns. We identified atypical bursting patterns dependent on temperature that were totally different from classical bursting patterns observed in R15 neurons of A. juliana . We classified these abnormal bursting patterns into type 1 and type 2; type 1 abnormal single bursts are composed of two kinds of spikes with a long interspike interval (ISI) followed by short ISI regular firing, while type 2 abnormal single bursts are composed of complex multiplets. To investigate the mechanism underlying the temperature dependence of abnormal bursting, we employed simulations using a modified Plant model and determined that the temperature dependence of type 2 abnormal bursting is related to temperaturedependent scaling factors and activation or inactivation of potassium or sodium channels.

Effect of Anti-glaucoma Agents on Myopic Retinoschisis

Purpose@#To evaluate the effect of intraocular pressure (IOP)-lowering medications on myopic retinoschisis. @*Methods@#The medical records of 33 patients (36 eyes) with myopic retinoschisis associated with pathologic myopia were reviewed retrospectively. The patients were divided into two groups: the study group comprising patients undergoing treatment with anti-glaucoma medications for suspected glaucoma; the control group comprising patients who did not use any IOP lowering medications. The changes in retinoschisis in the two groups were compared using the Spectralis domain optical coherence tomography thickness map protocol. @*Results@#The study group included 18 eyes (17 patients), and the control group included 18 eyes (16 patients). There were no significant differences between the 6-month and 12-month improvement or aggravation rates of the two groups (p = 0.513 and 0.137, respectively). However, after 18 months, the aggravation rate of retinoschisis was significantly lower in the study group (p = 0.003). The improvement / aggravation rate was 58.33% / 16.67% in the study group and 0% / 57.14% in the control group. @*Conclusions@#The use of IOP-lowering medications for more than a year may be useful for the management of retinoschisis associated with pathologic myopia.

Analysis of temperature-dependent abnormal bursting patterns of neurons in Aplysia

Temperature affects the firing pattern and electrical activity of neurons in animals, eliciting diverse responses depending on neuronal cell type. However, the mechanisms underlying such diverse responses are not well understood. In the present study, we performed in vitro recording of abdominal ganglia cells of Aplysia juliana , and analyzed their burst firing patterns. We identified atypical bursting patterns dependent on temperature that were totally different from classical bursting patterns observed in R15 neurons of A. juliana . We classified these abnormal bursting patterns into type 1 and type 2; type 1 abnormal single bursts are composed of two kinds of spikes with a long interspike interval (ISI) followed by short ISI regular firing, while type 2 abnormal single bursts are composed of complex multiplets. To investigate the mechanism underlying the temperature dependence of abnormal bursting, we employed simulations using a modified Plant model and determined that the temperature dependence of type 2 abnormal bursting is related to temperaturedependent scaling factors and activation or inactivation of potassium or sodium channels.

Effect of Anti-glaucoma Agents on Myopic Retinoschisis

Purpose@#To evaluate the effect of intraocular pressure (IOP)-lowering medications on myopic retinoschisis. @*Methods@#The medical records of 33 patients (36 eyes) with myopic retinoschisis associated with pathologic myopia were reviewed retrospectively. The patients were divided into two groups: the study group comprising patients undergoing treatment with anti-glaucoma medications for suspected glaucoma; the control group comprising patients who did not use any IOP lowering medications. The changes in retinoschisis in the two groups were compared using the Spectralis domain optical coherence tomography thickness map protocol. @*Results@#The study group included 18 eyes (17 patients), and the control group included 18 eyes (16 patients). There were no significant differences between the 6-month and 12-month improvement or aggravation rates of the two groups (p = 0.513 and 0.137, respectively). However, after 18 months, the aggravation rate of retinoschisis was significantly lower in the study group (p = 0.003). The improvement / aggravation rate was 58.33% / 16.67% in the study group and 0% / 57.14% in the control group. @*Conclusions@#The use of IOP-lowering medications for more than a year may be useful for the management of retinoschisis associated with pathologic myopia.

Spatial Learning and Motor Deficits in Vacuolar Protein Sorting-associated Protein 13b (Vps13b) Mutant Mouse

Vacuolar protein sorting-associated protein 13B (VPS13B), also known as COH1, is one of the VPS13 family members which is involved in transmembrane transport, Golgi integrity, and neuritogenesis. Mutations in the VPS13B gene are associated with Cohen syndrome and other cognitive disorders such as intellectual disabilities and autism spectrum disorder (ASD). However, the patho-physiology of VPS13B-associated cognitive deficits is unclear, in part, due to the lack of animal models. Here, we generated a Vps13b exon 2 deletion mutant mouse and analyzed the behavioral phenotypes. We found that Vps13b mutant mice showed reduced activity in open field test and significantly shorter latency to fall in the rotarod test, suggesting that the mutants have motor deficits. In addition, we found that Vps13b mutant mice showed deficits in spatial learning in the hidden platform version of the Morris water maze. The Vps13b mutant mice were normal in other behaviors such as anxiety-like behaviors, working memory and social behaviors. Our results suggest that Vps13b mutant mice may recapitulate key clinical symptoms in Cohen syndrome such as intellectual disability and hypotonia. Vps13b mutant mice may serve as a useful model to investigate the pathophysiology of VPS13B-associated disorders.

Inhibition of anterior cingulate cortex excitatory neuronal activity induces conditioned place preference in a mouse model of chronic inflammatory pain

The anterior cingulate cortex (ACC) is known for its role in perception of nociceptive signals and the associated emotional responses. Recent optogenetic studies, involving modulation of neuronal activity in the ACC, show that the ACC can modulate mechanical hyperalgesia. In the present study, we used optogenetic techniques to selectively modulate excitatory pyramidal neurons and inhibitory interneurons in the ACC in a model of chronic inflammatory pain to assess their motivational effect in the conditioned place preference (CPP) test. Selective inhibition of pyramidal neurons induced preference during the CPP test, while activation of parvalbumin (PV)-specific neurons did not. Moreover, chemogenetic inhibition of the excitatory pyramidal neurons alleviated mechanical hyperalgesia, consistent with our previous result. Our results provide evidence for the analgesic effect of inhibition of ACC excitatory pyramidal neurons and a prospective treatment for chronic pain.

Neuroglial Cells: An Overview of Their Physiological Roles and Abnormalities in Mental Disorders

The brain maintains homeostasis and normal microenvironment through dynamic interactions of neurons and neuroglial cells to perform the proper information processing and normal cognitive functions. Recent post-mortem investigations and animal model studies demonstrated that the various brain areas such as cerebral cortex, hippocampus and amygdala have abnormalities in neuroglial numbers and functions in subjects with mental illnesses including schizophrenia, dementia and mood disorders like major depression and bipolar disorder. These findings highlight the putative role and involvement of neuroglial cells in mental disorders. Herein I discuss the physiological roles of neuroglial cells such as astrocytes, oligodendrocytes, and microglia in maintaining normal brain functions and their abnormalities in relation to mental disorders. Finally, all these findings could serve as a useful starting point for potential therapeutic concept and drug development to cure unnatural behaviors and abnormal cognitive functions observed in mental disorders.

Simplified Correction of Ischemic Index in Diabetic Retinopathy Evaluated by Ultra-widefield Fluorescein Angiography

PURPOSE: To develop a novel, simplified method for correcting the ischemic index of nonperfused areas in diabetic retinopathy (DR). METHODS: We performed a retrospective review of 103 eyes with naive DR that underwent ultra-widefield angiography (UWFA) over a year. UWFAs were graded according to the quantity of retinal non-perfusion, and uncorrected ischemic index (UII) and corrected ischemic index (CII) were calculated using a simplified, novel method. RESULTS: The average differences between UII and CII in the non-proliferative DR group and the proliferative DR group were 0.7 +/- 0.9% in the 50% CII group, respectively. A CII >25% was critical for determining DR progression (p < 0.001). CONCLUSIONS: Distortion created by UWFA needs to be corrected because the difference between UII and CII in DR increases with the ischemic index.

Simplified Correction of Ischemic Index in Diabetic Retinopathy Evaluated by Ultra-widefield Fluorescein Angiography

PURPOSE: To develop a novel, simplified method for correcting the ischemic index of nonperfused areas in diabetic retinopathy (DR). METHODS: We performed a retrospective review of 103 eyes with naive DR that underwent ultra-widefield angiography (UWFA) over a year. UWFAs were graded according to the quantity of retinal non-perfusion, and uncorrected ischemic index (UII) and corrected ischemic index (CII) were calculated using a simplified, novel method. RESULTS: The average differences between UII and CII in the non-proliferative DR group and the proliferative DR group were 0.7 +/- 0.9% in the 50% CII group, respectively. A CII >25% was critical for determining DR progression (p < 0.001). CONCLUSIONS: Distortion created by UWFA needs to be corrected because the difference between UII and CII in DR increases with the ischemic index.

Comparison of Injection of Intravitreal Drugs with Standard Care in Macular Edema Secondary to Branch Retinal Vein Occlusion

PURPOSE: To compare the long-term efficacy and safety of intravitreal triamcinolon with or without rescue laser therapy (intravitreal triamcinolone injection [IVTA] group), bevacizumab with or without rescue laser treatment (intravitreal bevacizumab injection [IVB] group), or a combination of both with or without rescue laser therapy (IVTA + IVB group), with standard care for patients with macular edema secondary to branch retinal vein occlusion (BRVO). METHODS: We reviewed the medical records of 151 patients treated with intravitreal injection with or without rescue laser for treatment of macular edema caused by BRVO, and who were followed up at 1, 3, 6, 12, and 24 months. During the observation period, rescue grid laser or repeated intravitreal injection with initial drug was performed if recurrence of macular edema was confirmed. Visual acuity, change in visual acuity, and intraocular pressure were compared in each phase. RESULTS: Totals of 16%, 5.6%, and 0% of participants in the three groups showed significant visual loss of more than three lines of the Snellen chart at last follow-up. The IVTA group was the least effective treatment modality, with statistical significance. The development rates of elevated intraocular pressure were similar among the groups. CONCLUSIONS: Although IVTA yielded effects similar to those of standard grid photocoagulation based on the Standard Care vs Corticosteroid for Retinal Vein Occlusion study, IVB or IVTA + IVB with or without rescue laser treatment resulted in improvement in visual acuity at 24 months after the start of treatment and was associated with few serious adverse side effects. Thus, these approaches could be useful for treating macular edema arising secondary to BRVO.

Comparison of Injection of Intravitreal Drugs with Standard Care in Macular Edema Secondary to Branch Retinal Vein Occlusion

PURPOSE: To compare the long-term efficacy and safety of intravitreal triamcinolon with or without rescue laser therapy (intravitreal triamcinolone injection [IVTA] group), bevacizumab with or without rescue laser treatment (intravitreal bevacizumab injection [IVB] group), or a combination of both with or without rescue laser therapy (IVTA + IVB group), with standard care for patients with macular edema secondary to branch retinal vein occlusion (BRVO). METHODS: We reviewed the medical records of 151 patients treated with intravitreal injection with or without rescue laser for treatment of macular edema caused by BRVO, and who were followed up at 1, 3, 6, 12, and 24 months. During the observation period, rescue grid laser or repeated intravitreal injection with initial drug was performed if recurrence of macular edema was confirmed. Visual acuity, change in visual acuity, and intraocular pressure were compared in each phase. RESULTS: Totals of 16%, 5.6%, and 0% of participants in the three groups showed significant visual loss of more than three lines of the Snellen chart at last follow-up. The IVTA group was the least effective treatment modality, with statistical significance. The development rates of elevated intraocular pressure were similar among the groups. CONCLUSIONS: Although IVTA yielded effects similar to those of standard grid photocoagulation based on the Standard Care vs Corticosteroid for Retinal Vein Occlusion study, IVB or IVTA + IVB with or without rescue laser treatment resulted in improvement in visual acuity at 24 months after the start of treatment and was associated with few serious adverse side effects. Thus, these approaches could be useful for treating macular edema arising secondary to BRVO.

Efficacy of Intravitreal Anti-vascular Endothelial Growth Factor or Steroid Injection in Diabetic Macular Edema According to Fluid Turbidity in Optical Coherence Tomography

PURPOSE: To determine if short term effects of intravitreal anti-vascular endothelial growth factor or steroid injection are correlated with fluid turbidity, as detected by spectral domain optical coherence tomography (SD-OCT) in diabetic macular edema (DME) patients. METHODS: A total of 583 medical records were reviewed and 104 cases were enrolled. Sixty eyes received a single intravitreal bevacizumab injection (IVB) on the first attack of DME and 44 eyes received triamcinolone acetonide treatment (IVTA). Intraretinal fluid turbidity in DME patients was estimated with initialintravitreal SD-OCT and analyzed with color histograms from a Photoshop program. Central macular thickness and visual acuity using a logarithm from the minimum angle of resolution chart, were assessed at the initial period and 2 months after injections. RESULTS: Visual acuity and central macular thickness improved after injections in both groups. In the IVB group, visual acuity and central macular thickness changed less as the intraretinal fluid became more turbid. In the IVTA group, visual acuity underwent less change while central macular thickness had a greater reduction (r = -0.675, p = 0.001) as the intraretinal fluid was more turbid. CONCLUSIONS: IVB and IVTA injections were effective in reducing central macular thickness and improving visual acuity in DME patients. Further, fluid turbidity, which was detected by SD-OCT may be one of the indexes that highlight the influence of the steroid-dependent pathogenetic mechanism.

Bi-Coronal Separated Skull Fracture: A Unique and Fatal Type of Traumatic Head Injury in Infancy: A Case Report / 대한신경손상학회지

The infantile skull is malleable, and its sutures are tightly adhering to the underlying dura and venous sinus. These characteristics, in association with the small amount of total blood volume, can result in a specific fatal type of skull fracture, which is unique to infancy. The authors report a case of this injury, and stress the need to pay attention to the possibility of massive bleeding during operation in infants. A 23-month-old female baby presented with semicomatose mentality after sustaining injuries by falling from a second-floor. Plain skull films showed bi-frontal skull fracture crossing the midline. Computed tomography revealed an acute subdural hematoma along the right convexity with severe brain edema. In the emergency operation, the scalp incision exposed massive bleeding from the fracture site. The bleeding was identified as arising from the lacerated and widely separated sagittal sinus beneath the fracture. The patient entered hypovolemic shock immediately after the scalp incision, and died from severe brain edema two days after the trauma and surgery. This case implies that special care should be paid during the operation of patients that have skull fracture overlying the venous sinus, especially when the fracture line is separated.

Evidence-Based Korean Pharmacological Treatment Guideline for Depression, Revised Edition (III) : Dose Increment, Switching, Combination, and Augmentation Strategy in Antidepressant Therapy / 신경정신의학

OBJECTIVES: The aim of this study was to demonstrate the recommendations for antidepressant treatment strategy of dose increment, switching, combination, and augmentation therapy derived from Evidence-Based Korean Pharmacological Treatment Guideline for Depression, Revised Edition. METHODS: The guideline was developed through adaptation of 12 domestic and foreign clinical guidelines for depression, with key questions concerning pharmacotherapy of depression, and drawing of recommendations. RESULTS: The guideline strongly recommended dose increment, switching, and combination and augmentation therapy of antidepressant when patients with depression showed inadequate treatment outcomes from initial antidepressant treatment. The dose increment was strongly recommended when the patients had insufficient response from treatment with tricyclic antidepressants (TCAs), monoamine oxidase inhibitors, selective serotonin reuptake inhibitors (SSRIs), and serotonin and norepinephrine reuptake inhibitors (SNRIs). Switching from SSRI to non-SSRI was also strongly recommended. The combination of initial medication and other classes of antidepressants could benefit from treatment with TCAs, SSRIs, SNRIs, and noradrenergic and specific serotonergic antidepressants. Combination with norepinephrine and dopamine reuptake inhibitors or serotonin-2 antagonist/reuptake inhibitors was weakly recommended. The guideline strongly recommended use of the augmentation strategy of adding lithium or benzodiazepine to initial antidepressants. Augmentation of lamotrigine, T3, methylphenidate, and modafinil was weakly recommended. CONCLUSION: If the initial outcomes of antidepressant therapy are unsatisfactory to the patients the next-step strategies of dose increment, switching, combination and augmentation of antidepressants should be considered after rechecking the patients' drug compliance, dose, and diagnosis.

Effect of Intensity of Unconditional Stimulus on Reconsolidation of Contextual Fear Memory

Memory reconsolidation is ubiquitous across species and various memory tasks. It is a dynamic process in which memory is modified and/or updated. In experimental conditions, memory reconsolidation is usually characterized by the fact that the consolidated memory is disrupted by a combination of memory reactivation and inhibition of protein synthesis. However, under some experimental conditions, the reactivated memory is not disrupted by inhibition of protein synthesis. This so called "boundary condition" of reconsolidation may be related to memory strength. In Pavlovian fear conditioning, the intensity of unconditional stimulus (US) determines the strength of the fear memory. In this study, we examined the effect of the intensity of US on the reconsolidation of contextual fear memory. Strong contextual fear memory, which is conditioned with strong US, is not disrupted by inhibition of protein synthesis after its reactivation; however, a weak fear memory is often disrupted. This suggests that a US of strong intensity can inhibit reconsolidation of contextual fear memory.

A Computational Model of the Temperature-dependent Changes in Firing Patterns in Aplysia Neurons

We performed experiments using Aplysia neurons to identify the mechanism underlying the changes in the firing patterns in response to temperature changes. When the temperature was gradually increased from 11degrees C to 31degrees C the firing patterns changed sequentially from the silent state to beating, doublets, beating-chaos, bursting-chaos, square-wave bursting, and bursting-oscillation patterns. When the temperature was decreased over the same temperature range, these sequential changes in the firing patterns reappeared in reverse order. To simulate this entire range of spiking patterns we modified nonlinear differential equations that Chay and Lee made using temperature-dependent scaling factors. To refine the equations, we also analyzed the spike pattern changes in the presence of potassium channel blockers. Based on the solutions of these equations and potassium channel blocker experiments, we found that, as temperature increases, the maximum value of the potassium channel relaxation time constant, taun(t) increases, but the maximum value of the probabilities of openings for activation of the potassium channels, n(t) decreases. Accordingly, the voltage-dependent potassium current is likely to play a leading role in the temperature-dependent changes in the firing patterns in Aplysia neurons.