Climbing Fiber Signaling and Cerebellar Gain Control

The physiology of climbing fiber signals in cerebellar Purkinje cells has been studied since the early days of electrophysiology. Both the climbing fiber-evoked complex spike and the role of climbing fiber activity in the induction of long-term depression (LTD) at parallel fiber-Purkinje cell synapses have become hallmark features of cerebellar physiology. However, the key role of climbing fiber signaling in cerebellar motor learning has been challenged by recent reports of forms of synaptic and non-synaptic plasticity in the cerebellar cortex that do not involve climbing fiber activity, but might well play a role in cerebellar learning. Moreover, cerebellar LTD does not seem to strictly require climbing fiber activity. These observations make it necessary to re-evaluate the role of climbing fiber signaling in cerebellar function. Here, we argue that climbing fiber signaling is about adjusting relative probabilities for the induction of LTD and long-term potentiation (LTP) at parallel fiber synapses. Complex spike-associated, dendritic calcium transients control postsynaptic LTD and LTP induction. High calcium transients, provided by complex spike activity, do not only favor postsynaptic LTD induction, but simultaneously trigger retrograde cannabinoid signaling, which blocks the induction of presynaptic LTP. Plasticity of the climbing fiber input itself provides additional means to fine-tune complex spike associated calcium signaling and thus to adjust the gain of heterosynaptic climbing fiber control. In addition to dendritic calcium transients, climbing fiber activity leads to the release of the neuropeptide corticotropin-releasing factor (CRF), which facilitates LTD induction at both parallel fiber and climbing fiber synapses

Neural ensembles: Role of intrinsic excitability and its plasticity

Synaptic connectivity defines groups of neurons that engage in correlated activity during specific functional tasks. These co-active groups of neurons form ensembles, the operational units involved in, for example, sensory perception, motor coordination and memory (then called an engram). Traditionally, ensemble formation has been thought to occur via strengthening of synaptic connections via long-term potentiation (LTP) as a plasticity mechanism. This synaptic theory of memory arises from the learning rules formulated by Hebb and is consistent with many experimental observations. Here, we propose, as an alternative, that the intrinsic excitability of neurons and its plasticity constitute a second, non-synaptic mechanism that could be important for the initial formation of ensembles. Indeed, enhanced neural excitability is widely observed in multiple brain areas subsequent to behavioral learning. In cortical structures and the amygdala, excitability changes are often reported as transient, even though they can last tens of minutes to a few days. Perhaps it is for this reason that they have been traditionally considered as modulatory, merely supporting ensemble formation by facilitating LTP induction, without further involvement in memory function (memory allocation hypothesis). We here suggest−based on two lines of evidence—that beyond modulating LTP allocation, enhanced excitability plays a more fundamental role in learning. First, enhanced excitability constitutes a signature of active ensembles and, due to it, subthreshold synaptic connections become suprathreshold in the absence of synaptic plasticity (iceberg model). Second, enhanced excitability promotes the propagation of dendritic potentials toward the soma and allows for enhanced coupling of EPSP amplitude (LTP) to the spike output (and thus ensemble participation). This permissive gate model describes a need for permanently increased excitability, which seems at odds with its traditional consideration as a short-lived mechanism. We propose that longer modifications in excitability are made possible by a low threshold for intrinsic plasticity induction, suggesting that excitability might be on/off-modulated at short intervals. Consistent with this, in cerebellar Purkinje cells, excitability lasts days to weeks, which shows that in some circuits the duration of the phenomenon is not a limiting factor in the first place. In our model, synaptic plasticity defines the information content received by neurons through the connectivity network that they are embedded in. However, the plasticity of cell-autonomous excitability could dynamically regulate the ensemble participation of individual neurons as well as the overall activity state of an ensemble

Pengaruh Sales Growth, Profitabilitas, Capital Intensity dan Ukuran Perusahaan Terhadap Penghindaran Pajak Pada Perusahaan Subsektor Makanan dan Minuman yang Terdaftar di Bursa Efek Indonesia (BEI) Tahun 2019-2022

Penelitian ini bertujuan untuk membuktikan secara empiris pengaruh pertumbuhan penjuaIan, profitabiIitas, intensitas modal dan ukuran perusahaan terhadap penghindaran pajak. PopuIasi daIam peneIitian ini berjumIah 27 perusahaan dengan sampeI yang dipiIih sebanyak 13 perusahaan. SampeI ini diambiI menggunakan Metode Purposive SampIing berdasarkan sampeI yang memenuhi kriteria sebanyak 52 seIama 4 tahun pengamatan yang termasuk ke daIam Perusahaan Perbankan yang terdaftar di Bursa Efek Indonesia seIama tahun 2019-2022. Metode anaIisis data yang digunakan adaIah uji deskriptif, uji asumsi kIasik, uji regresi Iinier berganda, dan uji hipotesis dengan menggunakan SPSS Versi 29. Hasil peneIitian menunjukan bahwa sales growth secara parsiaI memiIiki pengaruh terhadap penghindaran pajak, profitabiIitas secara parsiaI tidak memiIiki pengaruh terhadap penghindaran pajak, capitaI intensity secara parsiaI tidak memiIiki pengaruh terhadap penghindaran pajak, ukuran perusahaan secara parsiaI memiIiki pengaruh terhadap penghindaran pajak,. Secara simuItan menunjukan terdapat pengaruh antara saIes growth, profitabiIitas, capitaI intensity, dan ukuran perusahaan terhadap penghindaran pajak.as

Pengaruh Sales Growth, Profitabilitas, Capital Intensity dan Ukuran Perusahaan Terhadap Penghindaran Pajak Pada Perusahaan Subsektor Makanan dan Minuman yang Terdaftar di Bursa Efek Indonesia (BEI) Tahun 2019-2022

Penelitian ini bertujuan untuk membuktikan secara empiris pengaruh pertumbuhan penjuaIan, profitabiIitas, intensitas modal dan ukuran perusahaan terhadap penghindaran pajak. PopuIasi daIam peneIitian ini berjumIah 27 perusahaan dengan sampeI yang dipiIih sebanyak 13 perusahaan. SampeI ini diambiI menggunakan Metode Purposive SampIing berdasarkan sampeI yang memenuhi kriteria sebanyak 52 seIama 4 tahun pengamatan yang termasuk ke daIam Perusahaan Perbankan yang terdaftar di Bursa Efek Indonesia seIama tahun 2019-2022. Metode anaIisis data yang digunakan adaIah uji deskriptif, uji asumsi kIasik, uji regresi Iinier berganda, dan uji hipotesis dengan menggunakan SPSS Versi 29. Hasil peneIitian menunjukan bahwa sales growth secara parsiaI memiIiki pengaruh terhadap penghindaran pajak, profitabiIitas secara parsiaI tidak memiIiki pengaruh terhadap penghindaran pajak, capitaI intensity secara parsiaI tidak memiIiki pengaruh terhadap penghindaran pajak, ukuran perusahaan secara parsiaI memiIiki pengaruh terhadap penghindaran pajak,. Secara simuItan menunjukan terdapat pengaruh antara saIes growth, profitabiIitas, capitaI intensity, dan ukuran perusahaan terhadap penghindaran pajak.asd

PANDANGAN MASYARAKAT TERHADAP HIDROPONIK DI DAERAH PERKOTAAN

Semakin hari jumlah penduduk di dunia semakin bertambah. Diperkirakan pada tahun 2050 jumlah penduduk di seluruh dunia mencapai 9,8 miliar jiwa. Hal ini disertai dengan meningkatnya kebutuhan akan lahan, jumlah lahan yang tersedia di dunia tidak akan bertambah sehingga lahan pertanian semakin sempit. Oleh karena itu, untuk mengatasi lahan pertanian yang mulai berkurang di daerah perkotaan ini diciptakanlah sistem pertanian baru yang tidak hanya dapat dikembangkan di lahan sempit, tetapi juga ramah lingkungan disebut hidroponik. Penelitian ini bertujuan untuk mengetahui dan menganalisis bagaimana pendapat masyarakat terhadap sistem pertanian hidroponik di daerah perkotaan Surabaya. Metode yang digunakan di laporan ini dalam menentukan pandangan masyarakat yaitu dimulai dengan survei kawasan sekitar di Surabaya, lalu mewawancarai masyarakat dan beberapa mahasiswa. Setelah itu, ditarik kesimpulan berdasarkan hasil wawancara. Berdasarkan opini-opini warga didapat hasil dari kuesioner sebesar rata-rata 67,5% setuju bahwa sistem hidroponik ini dapat membawa dampak positif bagi lingkungan maupun masyarakat. Kegiatan hidroponik ini dinilai sangat membantu masyarakat dalam belajar bagaimana melakukan sistem budidaya pertanian di lahan yang relatif sempit

Expression of a Protein Kinase C Inhibitor in Purkinje Cells Blocks Cerebellar LTD and Adaptation of the Vestibulo-Ocular Reflex

AbstractCerebellar long-term depression (LTD) is a model system for neuronal information storage that has an absolute requirement for activation of protein kinase C (PKC). It has been claimed to underlie several forms of cerebellar motor learning. Previous studies using various knockout mice (mGluR1, GluRδ2, glial fibrillary acidic protein) have supported this claim; however, this work has suffered from the limitations that the knockout technique lacks anatomical specificity and that functional compensation can occur via similar gene family members. To overcome these limitations, a transgenic mouse (called L7-PKCI) has been produced in which the pseudosubstrate PKC inhibitor, PKC[19–31], was selectively expressed in Purkinje cells under the control of the pcp-2(L7) gene promoter. Cultured Purkinje cells prepared from heterozygous or homozygous L7-PKCI embryos showed a complete blockade of LTD induction. In addition, the compensatory eye movements of L7-PKCI mice were recorded during vestibular and visual stimulation. Whereas the absolute gain, phase, and latency values of the vestibulo-ocular reflex and optokinetic reflex of the L7-PKCI mice were normal, their ability to adapt their vestibulo-ocular reflex gain during visuo-vestibular training was absent. These data strongly support the hypothesis that activation of PKC in the Purkinje cell is necessary for cerebellar LTD induction, and that cerebellar LTD is required for a particular form of motor learning, adaptation of the vestibulo-ocular reflex

Activity-Dependent Plasticity of Spike Pauses in Cerebellar Purkinje Cells

The plasticity of intrinsic excitability has been described in several types of neurons, but the significance of non-synaptic mechanisms in brain plasticity and learning remains elusive. Cerebellar Purkinje cells are inhibitory neurons that spontaneously fire action potentials at high frequencies and regulate activity in their target cells in the cerebellar nuclei by generating a characteristic spike burst-pause sequence upon synaptic activation. Using patch-clamp recordings from mouse Purkinje cells, we find that depolarization-triggered intrinsic plasticity enhances spike firing and shortens the duration of spike pauses. Pause plasticity is absent from mice lacking SK2-type potassium channels (SK2-/- mice) and in occlusion experiments using the SK channel blocker apamin, while apamin wash-in mimics pause reduction. Our findings demonstrate that spike pauses can be regulated through an activity-dependent, exclusively non-synaptic, SK2 channel-dependent mechanism and suggest that pause plasticity-by altering the Purkinje cell output-may be crucial to cerebellar information storage and learning

The Role of Complex Treatment in Mixed Leg Ulcers – A Case Report of Vascular, Surgical and Physical Therapy

BACKGROUND: Leg ulcers are a burden to patients, their families and society. The second most common cause of chronic leg ulcers is the mixed arterio-venous type. An 80-year-old female patient presented to our department due to painful enlarging chronic leg ulcer of mixed arteriovenous origin on her left lower leg. She suffered from peripheral arterial occlusive disease stage I and chronic venous insufficiency Widmer grade IIIa, and a number of comorbidities.AIM: The aim of our ulcer treatment was a complete and stable wound closure that was hampered by arterial occlusion, exposed tendon, and renal insiffuciency.CASE REPORT: To improve the prognosis for ulcer surgery, we performed percutaneous transluminal angioplasty, transcutaneous CO2 and deep ulcer shaving. The wound was closed by sandwich transplantation using elastin-collagen dermal template and meshed split skin graft. She had a 100% graft take with rapid reduction of severe wound pain.CONCLUSION: Complex approaches are necessary, to gain optimum results in leg ulcer therapy in mixed leg ulcers. Therapeutic nihilism should be abandonend

Restless Legs Syndrome Prevalence and Clinical Correlates Among Psychiatric Inpatients: A Multicenter Study.

Background There are only limited reports on the prevalence of restless legs syndrome (RLS) in patients with psychiatric disorders. The present study aimed to evaluate the prevalence and clinical correlates in psychiatric inpatients in Germany and Switzerland. Methods This is a multicenter cross-sectional study of psychiatric inpatients with an age above 18 years that were diagnosed and evaluated face-to-face using the International RLS Study Group criteria (IRLSSG) and the International RLS severity scale (IRLS). In addition to sociodemographic and biometric data, sleep quality and mood were assessed using the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), the Epworth Sleepiness Scale (ESS), and the Patient Health Questionnaire (PHQ-9). In addition to univariate statistics used to describe and statistically analyze differences in variables of interest between patients with and without RLS, a logistic model was employed to identify predictors for the occurrence of RLS. Results The prevalence of RLS in a sample of 317 psychiatric inpatients was 16.4%, and 76.9% of these were diagnosed with RLS for the first time. RLS severity was moderate to severe (IRLS ± SD: 20.3 ± 8.4). The prevalences in women (p = 0.0036) and in first-degree relatives with RLS (p = 0.0108) as well as the body mass index (BMI, p = 0.0161) were significantly higher among patients with RLS, while alcohol consumption was significantly lower in the RLS group. With the exception of atypical antipsychotics, treatment with psychotropic drugs was not associated with RLS symptoms. Regarding subjective sleep quality and mood, scores of the PSQI (p = 0.0007), ISI (p = 0.0003), and ESS (p = 0.0005) were higher in patients with RLS, while PHQ-9 scores were not different. A logistic regression analysis identified gender (OR 2.67; 95% CI [1.25; 5.72]), first-degree relatives with RLS (OR 3.29; 95% CI [1.11; 9.73], ESS score (OR 1.09; 95% CI [1.01; 1.17]), and rare alcohol consumption (OR 0.45; 95% CI [0.22; 0.94] as predictors for RLS. Conclusions Clinically significant RLS had a high prevalence in psychiatric patients. RLS was associated with higher BMI, impaired sleep quality, and lower alcohol consumption. A systematic assessment of restless legs symptoms might contribute to improve the treatment of psychiatric patients