Notes

PD-L1 PET/CT photo along with radiolabeled durvalumab inside patients with innovative period non-small mobile cancer of the lung.
Experiments have shown that the same stimulation pattern that causes Long-Term Potentiation in proximal synapses, will induce Long-Term Depression in distal ones. In order to understand these, and other, surprising observations we use a phenomenological model of Hebbian plasticity at the location of the synapse. Our model describes the Hebbian condition of joint activity of pre- and postsynaptic neurons in a compact form as the interaction of the glutamate trace left by a presynaptic spike with the time course of the postsynaptic voltage. Instead of simulating the voltage, we test the model using experimentally recorded dendritic voltage traces in hippocampus and neocortex. We find that the time course of the voltage in the neighborhood of a stimulated synapse is a reliable predictor of whether a stimulated synapse undergoes potentiation, depression, or no change. Our computational model can explain the existence of different -at first glance seemingly paradoxical- outcomes of synaptic potentiation and depression experiments depending on the dendritic location of the synapse and the frequency or timing of the stimulation.[This corrects the article DOI 10.3389/fninf.2020.00041.].Many current computational models that aim to simulate cortical and hippocampal modules of the brain depend on artificial neural networks. However, such classical or even deep neural networks are very slow, sometimes taking thousands of trials to obtain the final response with a considerable amount of error. The need for a large number of trials at learning and the inaccurate output responses are due to the complexity of the input cue and the biological processes being simulated. This article proposes a computational model for an intact and a lesioned cortico-hippocampal system using quantum-inspired neural networks. This cortico-hippocampal computational quantum-inspired (CHCQI) model simulates cortical and hippocampal modules by using adaptively updated neural networks entangled with quantum circuits. The proposed model is used to simulate various classical conditioning tasks related to biological processes. The output of the simulated tasks yielded the desired responses quickly and efficiently compared with other computational models, including the recently published Green model.Aging is associated with subjective memory complaints. Approximately half of those with subjective memory complaints have objective cognitive impairment. Previous studies have provided evidence of an association between genetic risk for Alzheimer's disease (AD) and dementia progression. Also, aging is a significant risk factor for vascular pathology that may underlie at least some of the cognitive changes. This study investigates the relative contribution of subjective cognitive complaints (SCC), vascular function, and genetic risk for dementia in predicting objective cognitive performance. Multiple regression and relative importance analysis were used to investigate the relative contribution of vascular function, self-reported SCC, and dementia genetic risk, in predicting objective cognition in a sample of 238 healthy community-dwelling older adults. Age, sex, premorbid cognitive abilities, subjective verbal memory complaints, higher cerebrovascular blood flow during submaximal exercise, and certain dementia risk alleles were significant predictors of worse objective verbal memory performance (p less then 0.001, R2 = 35.2-36.4%). Using relative importance analysis, subjective verbal memory complaints, and certain dementia risk alleles contributed more variance than cerebrovascular measures. These results suggest that age-related changes in memory in healthy older adults can be predicted by subjective memory complaints, genetic risk, and to a lesser extent, cerebrovascular function.The ventral tegmental area (VTA) underlies motivation and reinforcement of natural rewards. The lateral preoptic area (LPO) is an anterior hypothalamic brain region that sends direct projections to the VTA and to other brain structures known to regulate VTA activity. Here, we investigated the functional connection between the LPO and subpopulations of VTA neurons and explored the reinforcing and valence qualities of the LPO in rats. We found that the LPO and the LPO→VTA pathway inhibit the activity of VTA GABA neurons and have mixed effects on VTA dopamine neurons. Furthermore, we found that the LPO supports operant responding but drives avoidance, and we explored the apparent discrepancy between these two results. Finally, using fiber photometry, we show that the LPO signals aversive events but not rewarding events. Together, our findings demonstrate that the LPO modulates the activity of the VTA and drives motivated behavior and represents an overlooked modulator of reinforcement.The ability of humans and animals to localize the source of a sound in a complex acoustic environment facilitates communication and survival. Two cues are used for sound localization at horizontal planes, interaural time and level differences (ITD and ILD), which are analyzed by distinct neural circuits in the brainstem. Here, we review the studies on metabotropic glutamate receptor (mGluR)-mediated neuromodulation of both intrinsic and synaptic properties of brainstem neurons in these circuits. Both mammalian and avian animal models have been used, with each having their advantages that are not present in the other. For the mammalian model, we discuss mGluR neuromodulation in the ILD circuit, with an emphasis on the recent discovery of differential modulation of synaptic transmission of different transmitter release modes. For the avian model, we focus on reviewing mGluR neuromodulation in the ITD pathway, with an emphasis on tonotopic distribution and synaptic plasticity of mGluR modulation in coincidence detector neurons. Future works are proposed to further investigate the functions and mechanisms of mGluRs in the sound localization circuits.During the last 50 years, the serotonergic (5-HT) system was reported to exert a complex modulation of locomotor activity. Here, we focus on two key factors that likely contribute to such complexity. First, locomotion is modulated directly and indirectly by 5-HT neurons. The locomotor circuitry is directly innervated by 5-HT neurons in the caudal brainstem and spinal cord. Also, indirect control of locomotor activity results from ascending projections of 5-HT cells in the rostral brainstem that innervate multiple brain centers involved in motor action planning. Second, each approach used to manipulate the 5-HT system likely engages different 5-HT-dependent mechanisms. This includes the recruitment of different 5-HT receptors, which can have excitatory or inhibitory effects on cell activity. These receptors can be located far or close to the 5-HT release sites, making their activation dependent on the level of 5-HT released. Here we review the activity of different 5-HT nuclei during locomotor activity, and the locomotor effects of 5-HT precursors, exogenous 5-HT, selective 5-HT reuptake inhibitors (SSRI), electrical or chemical stimulation of 5-HT neurons, genetic deletions, optogenetic and chemogenetic manipulations. We highlight both the coherent and controversial aspects of 5-HT modulation of locomotor activity from basal vertebrates to mammals. This mini review may hopefully inspire future studies aiming at dissecting the complex effects of 5-HT on locomotor function.The retrosplenial cortex forms part of the cingulate cortex and is involved in memory and navigation. It is ventral region, the granular retrosplenial cortex, or GRSC is characterized by the presence, of small pyramidal neurons with a distinctive late-spiking (LS) firing pattern in layer 2/3. Using in vitro brain slices of the mouse GRSC we have studied the electrophysiological properties and synaptic responses of these LS neurons, comparing them with neighboring non-LS pyramidal neurons. LS and non-LS neurons showed different responses during cortical propagation of epileptiform discharges. All non-LS neurons generated large supra-threshold excitatory responses that generated bursts of action potentials. Contrastingly, the LS neurons showed small, and invariably subthreshold excitatory synaptic potentials. Coelenterazine nmr Although both types of pyramidal neurons were readily intermingled in the GRSC, we observed differences in their innervation by cortico-cortical axons. The application of glutamate to activate cortical neuons, and that the two types of neurons are incorporated in different cortico-cortical neuronal circuits. This strongly suggests that the functional organization of the dorsal part of the GRSC is based on independent cortico-cortical circuits (among other elements).Alzheimer's disease (AD), the most common chronic neurodegenerative disorder, has complex neuropathology. The principal neuropathological hallmarks of the disease are the deposition of extracellular β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) comprised of hyperphosphorylated tau (p-tau) protein. These changes occur with neuroinflammation, a compromised blood-brain barrier (BBB) integrity, and neuronal synaptic dysfunction, all of which ultimately lead to neuronal cell loss and cognitive deficits in AD. Aβ1-42 was stereotaxically administered bilaterally into the CA1 region of the hippocampi of 18-month-old male C57BL/6 mice. link2 This study aimed to characterize, utilizing immunohistochemistry and behavioral testing, the spatial and temporal effects of Aβ1-42 on a broad set of parameters characteristic of AD p-tau, neuroinflammation, vascular pathology, pyramidal cell survival, and behavior. Three days after Aβ1-42 injection and before significant neuronal cell loss was detected, acute neuroinflammatmmatory, vascular, and p-tau induced pathology occurring in the AD human brain that lead to cognitive deficits.
Freezing of gait (FOG) is a common disabling motor symptom in Parkinson's disease (PD), but the potential pathogenic mechanisms are still unclear.

A total of 22 patients with PD with FOG (PD-FOG), 28 patients with PD without FOG (PD-nFOG), and 33 healthy controls (HCs) were recruited in this study. Degree centrality (DC)-a graph theory-based measurement of global connectivity at the voxel level by measuring the number of instantaneous functional connections between one region and the rest of the brain-can map brain hubs with high sensitivity, specificity, and reproducibility. DC was used to explore alterations in the centrality of PD-FOG correlated with brain node levels. PD-FOG cognitive network dysfunction was further revealed via a seed-based functional connectivity (FC) analysis. link3 In addition, correlation analyses were carried out between clinical symptoms and acquired connectivity measurement.

Compared to the PD-nFOG group, the PD-FOG group showed remarkably increased DC values in the right middle frontal gyrus (RMFG). There were no significant differences in other gray matter regions. Importantly, the clinical severity of FOG was related to the mean DC values in the RMFG. This brain region served as a seed in secondary seed-based FC analysis, and we further found FC changes in the right precuneus, right inferior frontal gyrus, right superior frontal gyrus (SFG), and cerebellum.

Increased RMFG activity and FC network alterations in the middle frontal cortex with the precuneus, inferior, and SFG, and the cerebellum may have great potential in brain dysfunction in PD with FOG.
Increased RMFG activity and FC network alterations in the middle frontal cortex with the precuneus, inferior, and SFG, and the cerebellum may have great potential in brain dysfunction in PD with FOG.
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