scholarly journals Robustness of neuronal tuning to binaural sound localization cues against age-related loss of inhibitory synaptic inputs

2021 ◽  
Vol 17 (7) ◽  
pp. e1009130
Author(s):  
Go Ashida ◽  
Daniel J. Tollin ◽  
Jutta Kretzberg
Keyword(s):  
Sound Localization ◽  
Functional Performance ◽  
Low Voltage ◽  
Modulation Depth ◽  
Potassium Conductance ◽  
Recovery Process ◽  
Homeostatic Plasticity ◽  
Functional Changes ◽  
Synaptic Inputs ◽  
Age Related

Sound localization relies on minute differences in the timing and intensity of sound arriving at both ears. Neurons of the lateral superior olive (LSO) in the brainstem process these interaural disparities by precisely detecting excitatory and inhibitory synaptic inputs. Aging generally induces selective loss of inhibitory synaptic transmission along the entire auditory pathways, including the reduction of inhibitory afferents to LSO. Electrophysiological recordings in animals, however, reported only minor functional changes in aged LSO. The perplexing discrepancy between anatomical and physiological observations suggests a role for activity-dependent plasticity that would help neurons retain their binaural tuning function despite loss of inhibitory inputs. To explore this hypothesis, we use a computational model of LSO to investigate mechanisms underlying the observed functional robustness against age-related loss of inhibitory inputs. The LSO model is an integrate-and-fire type enhanced with a small amount of low-voltage activated potassium conductance and driven with (in)homogeneous Poissonian inputs. Without synaptic input loss, model spike rates varied smoothly with interaural time and level differences, replicating empirical tuning properties of LSO. By reducing the number of inhibitory afferents to mimic age-related loss of inhibition, overall spike rates increased, which negatively impacted binaural tuning performance, measured as modulation depth and neuronal discriminability. To simulate a recovery process compensating for the loss of inhibitory fibers, the strength of remaining inhibitory inputs was increased. By this modification, effects of inhibition loss on binaural tuning were considerably weakened, leading to an improvement of functional performance. These neuron-level observations were further confirmed by population modeling, in which binaural tuning properties of multiple LSO neurons were varied according to empirical measurements. These results demonstrate the plausibility that homeostatic plasticity could effectively counteract known age-dependent loss of inhibitory fibers in LSO and suggest that behavioral degradation of sound localization might originate from changes occurring more centrally.

scholarly journals Neuronal and Synaptic Plasticity in the Visual Thalamus in Mouse Models of Glaucoma

2021 ◽  
Vol 14 ◽  
Author(s):  
Matthew J. Van Hook ◽  
Corrine Monaco ◽  
Elizabeth R. Bierlein ◽  
Jennie C. Smith
Keyword(s):  
Mouse Models ◽  
Ganglion Cells ◽  
Brain Regions ◽  
Synaptic Function ◽  
Homeostatic Plasticity ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Intrinsic Excitability ◽  
Dependent Manner ◽  
Functional Changes ◽  
Synaptic Inputs

Homeostatic plasticity plays important role in regulating synaptic and intrinsic neuronal function to stabilize output following perturbations to circuit activity. In glaucoma, a neurodegenerative disease of the visual system commonly associated with elevated intraocular pressure (IOP), the early disease is associated with altered synaptic inputs to retinal ganglion cells (RGCs), changes in RGC intrinsic excitability, and deficits in optic nerve transport and energy metabolism. These early functional changes can precede RGC degeneration and are likely to alter RGC outputs to their target structures in the brain and thereby trigger homeostatic changes in synaptic and neuronal properties in those brain regions. In this study, we sought to determine whether and how neuronal and synaptic function is altered in the dorsal lateral geniculate nucleus (dLGN), an important RGC projection target in the thalamus, and how functional changes related to IOP. We accomplished this using patch-clamp recordings from thalamocortical (TC) relay neurons in the dLGN in two established mouse models of glaucoma—the DBA/2J (D2) genetic mouse model and an inducible glaucoma model with intracameral microbead injections to elevate IOP. We found that the intrinsic excitability of TC neurons was enhanced in D2 mice and these functional changes were mirrored in recordings of TC neurons from microbead-injected mice. Notably, many neuronal properties were correlated with IOP in older D2 mice, when IOP rises. The frequency of miniature excitatory synaptic currents (mEPSCs) was reduced in 9-month-old D2 mice, and vGlut2 staining of RGC synaptic terminals was reduced in an IOP-dependent manner. These data suggest that glaucoma-associated changes to neuronal excitability and synaptic inputs in the dLGN might represent a combination of both stabilizing/homeostatic plasticity and pathological dysfunction.

scholarly journals Morpho-functional changes of cardiac telocytes in isolated atrial amyloidosis in patients with atrial fibrillation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tatyana V. Sukhacheva ◽  
Natalia V. Nizyaeva ◽  
Maria V. Samsonova ◽  
Andrey L. Cherniaev ◽  
Artem A. Burov ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Mitral Valve Regurgitation ◽  
Ultrastructural Level ◽  
Cardiomyocyte Hypertrophy ◽  
Myocardial Remodeling ◽  
Valve Regurgitation ◽  
Atrial Myocardium ◽  
Functional Changes ◽  
Age Related ◽  
Transitional Forms

AbstractTelocytes are interstitial cells with long, thin processes by which they contact each other and form a network in the interstitium. Myocardial remodeling of adult patients with different forms of atrial fibrillation (AF) occurs with an increase in fibrosis, age-related isolated atrial amyloidosis (IAA), cardiomyocyte hypertrophy and myolysis. This study aimed to determine the ultrastructural and immunohistochemical features of cardiac telocytes in patients with AF and AF + IAA. IAA associated with accumulation of atrial natriuretic factor was detected in 4.3–25% biopsies of left (LAA) and 21.7–41.7% of right (RAA) atrial appendage myocardium. Telocytes were identified at ultrastructural level more often in AF + IAA, than in AF group and correlated with AF duration and mitral valve regurgitation. Telocytes had ultrastructural signs of synthetic, proliferative, and phagocytic activity. Telocytes corresponded to CD117+, vimentin+, CD34+, CD44+, CD68+, CD16+, S100-, CD105- immunophenotype. No significant differences in telocytes morphology and immunophenotype were found in patients with various forms of AF. CD68-positive cells were detected more often in AF + IAA than AF group. We assume that in aged AF + IAA patients remodeling of atrial myocardium provoked transformation of telocytes into “transitional forms” combining the morphological and immunohistochemical features with signs of fibroblast-, histiocyte- and endotheliocyte-like cells.

scholarly journals Molecular and Supramolecular Structure of the Mitochondrial Oxidative Phosphorylation System: Implications for Pathology

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 242
Author(s):  
Salvatore Nesci ◽  
Fabiana Trombetti ◽  
Alessandra Pagliarani ◽  
Vittoria Ventrella ◽  
Cristina Algieri ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Mitochondrial Permeability Transition ◽  
Ros Generation ◽  
Protonmotive Force ◽  
Mitochondrial Oxidative Phosphorylation ◽  
F1fo Atp Synthase ◽  
Functional Changes ◽  
Age Related ◽  
Mitochondrial Functions

Under aerobic conditions, mitochondrial oxidative phosphorylation (OXPHOS) converts the energy released by nutrient oxidation into ATP, the currency of living organisms. The whole biochemical machinery is hosted by the inner mitochondrial membrane (mtIM) where the protonmotive force built by respiratory complexes, dynamically assembled as super-complexes, allows the F1FO-ATP synthase to make ATP from ADP + Pi. Recently mitochondria emerged not only as cell powerhouses, but also as signaling hubs by way of reactive oxygen species (ROS) production. However, when ROS removal systems and/or OXPHOS constituents are defective, the physiological ROS generation can cause ROS imbalance and oxidative stress, which in turn damages cell components. Moreover, the morphology of mitochondria rules cell fate and the formation of the mitochondrial permeability transition pore in the mtIM, which, most likely with the F1FO-ATP synthase contribution, permeabilizes mitochondria and leads to cell death. As the multiple mitochondrial functions are mutually interconnected, changes in protein composition by mutations or in supercomplex assembly and/or in membrane structures often generate a dysfunctional cascade and lead to life-incompatible diseases or severe syndromes. The known structural/functional changes in mitochondrial proteins and structures, which impact mitochondrial bioenergetics because of an impaired or defective energy transduction system, here reviewed, constitute the main biochemical damage in a variety of genetic and age-related diseases.

scholarly journals The Impact of Oxidative Stress on Blood-Retinal Barrier Physiology in Age-Related Macular Degeneration

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 64
Author(s):  
Annamaria Tisi ◽  
Marco Feligioni ◽  
Maurizio Passacantando ◽  
Marco Ciancaglini ◽  
Rita Maccarone
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Blood Retinal Barrier ◽  
Functional Changes ◽  
Beneficial Effects ◽  
Age Related ◽  
The Impact

The blood retinal barrier (BRB) is a fundamental eye component, whose function is to select the flow of molecules from the blood to the retina and vice-versa, and its integrity allows the maintenance of a finely regulated microenvironment. The outer BRB, composed by the choriocapillaris, the Bruch’s membrane, and the retinal pigment epithelium, undergoes structural and functional changes in age-related macular degeneration (AMD), the leading cause of blindness worldwide. BRB alterations lead to retinal dysfunction and neurodegeneration. Several risk factors have been associated with AMD onset in the past decades and oxidative stress is widely recognized as a key factor, even if the exact AMD pathophysiology has not been exactly elucidated yet. The present review describes the BRB physiology, the BRB changes occurring in AMD, the role of oxidative stress in AMD with a focus on the outer BRB structures. Moreover, we propose the use of cerium oxide nanoparticles as a new powerful anti-oxidant agent to combat AMD, based on the relevant existing data which demonstrated their beneficial effects in protecting the outer BRB in animal models of AMD.

scholarly journals Simulation of Dendritic CaV1.3 Channels in Cat Lumbar Motoneurons: Spatial Distribution

2005 ◽  
Vol 94 (6) ◽  
pp. 3961-3974 ◽  
Author(s):  
Sherif M. ElBasiouny ◽  
David J. Bennett ◽  
Vivian K. Mushahwar
Keyword(s):  
Spatial Distribution ◽  
Low Voltage ◽  
Dendritic Tree ◽  
Triceps Surae ◽  
Spinal Motoneurons ◽  
Functional Interaction ◽  
Intermediate Band ◽  
Synaptic Inputs ◽  
Persistent Inward Current ◽  
Adult Cat

We used computer simulations to study the dendritic spatial distribution of low voltage-activated L-type calcium (CaV1.3 type) channels, which mediate hysteretic persistent inward current (PIC) in spinal motoneurons. This study was prompted by the growing experimental evidence of the functional interactions between synaptic inputs and active conductances over the motoneuron dendritic tree. A compartmental cable model of an adult cat α-motoneuron was developed in NEURON simulation environment constituting the detailed morphology of type-identified triceps surae α-motoneuron and realistic distribution of group Ia afferent-to-motoneuron contacts. Simulations of different distributions of CaV1.3 channels were conducted and the resultant behavior was compared to experimental data. Our results suggest that CaV1.3 channels do not uniformly cover the whole motoneuron dendritic tree. Instead, their distribution is similar to that of synaptic contacts. We found that CaV1.3 channels are primarily localized to a wide intermediate band overlapping with the dendritic Ia-synaptic territory at dendritic distances of 300 to 850 μm (0.62 ± 0.21λ) from the soma in triceps surae α-motoneurons. These findings explain the functional interaction between synaptic inputs and the CaV1.3 channels over the motoneuron dendritic tree.

16 and 24 Gy Low-voltage X-ray Irradiation With Ranibizumab Therapy for Neovascular Age-Related Macular Degeneration: 12-Month Outcomes

2013 ◽  
Vol 155 (6) ◽  
pp. 1000-1008.e2 ◽  
Author(s):  
Virgilio Morales-Canton ◽  
Hugo Quiroz-Mercado ◽  
Raul Velez-Montoya ◽  
Alicia Zavala-Ayala ◽  
Andrew A. Moshfeghi ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Low Voltage ◽  
Age Related Macular Degeneration ◽  
X Ray ◽  
Age Related

Constipation in patients with comorbidity

2021 ◽  
Author(s):  
Е.А. Лялюкова ◽  
Е.Н. Логинова
Keyword(s):  
Gastrointestinal Tract ◽  
Neurological Diseases ◽  
The Elderly ◽  
Lifestyle Changes ◽  
Secretory Cells ◽  
Endocrine Disorders ◽  
Silver Age ◽  
Functional Changes ◽  
Slowing Down ◽  
Age Related

Пациенты пожилого и старческого возраста в силу физиологических причин и коморбидной патологии имеют высокий риск развития запора. Причиной запора чаще всего являются алиментарные факторы и возраст-ассоциированные заболевания и повреждения толстой кишки (дивертикулярная болезнь, ишемия толстой кишки, ректоцеле, геморрой и другие); метаболические, эндокринные расстройства и неврологические заболевания. Возрастные анатомические, структурные и функциональные изменения пищеварительной системы вносят свой вклад в развитие запоров у пожилых. У пациентов «серебряного возраста» отмечено увеличение длины желудочно-кишечного тракта, прогрессирование атрофических, склеротических изменений слизистой и подслизистой оболочки, снижение количества секреторных клеток, замещение мышечных волокон соединительной тканью и др. Все это способствует замедлению транзита по желудочно-кишечному тракту и нарушению акта дефекации. Образ жизни пожилых людей также может способствовать развитию запора. Низкое содержание в рационе клетчатки, употребление преимущественно термически обработанной пищи, нарушение ритма питания (прием пищи 1-2 раза в день) являются одной из причин возникновения запоров у пожилых, чему способствуют трудности при жевании вследствие стоматологических проблем. Колоноскопия показана всем пациентам пожилого и старческого возраста с запором, а выявление «симптомов тревоги» необходимо проводить при каждом визите пациента. Вне зависимости от причины вторичного запора, все пациенты должны осуществлять ряд мер немедикаментозного характера, включающих изменение образа жизни, диету с включением достаточного количества клетчатки и потребление жидкости. Физические методы лечения могут включать лечебную гимнастику, массаж толстой кишки для стимуляции моторной активности кишечника в определенное время. При неэффективности немедикаментозных мероприятий рекомендуется использование осмотических слабительных, а также средств, увеличивающих объем каловых масс. Высокая эффективность и безопасность псиллиума позволяет рекомендовать его в лечении хронического запора у пожилых пациентов. Elderly and senile patients, due to physiological reasons and comorbid pathology, have a high risk of constipation. The causes of constipation are more often nutritional factors and age-associated diseases and damage to the colon (diverticular disease, colon ischemia, rectocele, hemorrhoids, and others); metabolic, endocrine disorders and neurological diseases. Age-related anatomical, structural and functional changes in the digestive system contribute to the development of constipation in the elderly. In patients of «silver age», there was an increase in the length of the gastrointestinal tract, the progression of atrophic, sclerotic changes in the mucous and submucosa, a decrease in the number of secretory cells, replacement of muscle fibers with connective tissue, etc. All this contributes to the slowing down of transit through the gastrointestinal tract and the violation of the act of defecation. Elderly lifestyles can also contribute to constipation. The low fiber content in the diet, the use of mainly thermally processed food, the violation of the rhythm of the diet (eating 1-2 times a day) are one of the causes of constipation in the elderly, which is facilitated by difficulty in chewing due to dental problems. Colonoscopy is ordered for all elderly and senile patients with constipation, and the identification of «anxiety symptoms» should be carried out at each patient visit. Regardless of the cause of secondary constipation, all patients should take a number of non-pharmacological measures, including lifestyle changes, a diet with adequate fiber, and fluid intake. Physical therapies may include medical gymnastics, colon massage to stimulate bowel movement at specific times. If non-drug measures are ineffective, it is recommended to use osmotic laxatives, as well as agents that increase the volume of feces. Psyllium supplementation is recommended for treatment of chronic constipation in elderly patients due to its high efficacy and safety.

scholarly journals Neuronal and synaptic plasticity in the visual thalamus in mouse models of glaucoma

2020 ◽  
Author(s):  
Matthew J. Van Hook ◽  
Corrine Monaco ◽  
Jennie C. Smith
Keyword(s):  
Mouse Models ◽  
Ganglion Cells ◽  
Brain Regions ◽  
Synaptic Function ◽  
Homeostatic Plasticity ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Intrinsic Excitability ◽  
Dependent Manner ◽  
Functional Changes ◽  
Genetic Mouse Model

AbstractHomeostatic plasticity plays important roles in regulating synaptic and intrinsic neuronal function to stabilize output following perturbations to circuit activity. In glaucoma, a neurodegenerative disease of the visual system commonly associated with elevated intraocular pressure (IOP), early disease is associated with altered synaptic inputs to retinal ganglion cells (RGCs), changes in RGC intrinsic excitability, and deficits in optic nerve transport and energy metabolism. These early functional changes can precede RGC degeneration and are likely to alter RGC outputs to their target structures in the brain and thereby trigger homeostatic changes in synaptic and neuronal properties in those brain regions. In this study, we sought to determine whether and how neuronal and synaptic function is altered in the dorsal lateral geniculate nucleus (dLGN), an important RGC projection target in the thalamus, and how functional changes relate to IOP. We accomplished this using patch-clamp recordings from thalamocortical (TC) relay neurons in the dLGN in two established mouse models of glaucoma – the DBA/2J (D2) genetic mouse model and an inducible glaucoma model with intracameral microbead injections to elevate IOP. We found that the intrinsic excitability of TC neurons was enhanced in D2 mice and these functional changes were mirrored in recordings of TC neurons from microbead-injected mice. Notably, many neuronal properties were correlated with IOP in older D2 mice, but not younger D2 mice or microbead-injected mice. The frequency of miniature excitatory synaptic currents (mEPSCs) was reduced in both ages of D2 mice, and vGlut2 staining of RGC synaptic terminals was reduced in an IOP-dependent manner in older D2 mice. Among D2 mice, functional changes observed in younger mice without elevated IOP were distinct from those observed in older mice with elevated IOP and RGC degeneration, suggesting that glaucoma-associated changes to neurons in the dLGN might represent a combination of stabilizing/homeostatic plasticity at earlier stages and pathological dysfunction at later stages.

scholarly journals Potential Benefits of a Minimal Dose Eccentric Resistance Training Paradigm to Combat Sarcopenia and Age-Related Muscle and Physical Function Deficits in Older Adults

2021 ◽  
Vol 12 ◽  
Author(s):  
Sara A. Harper ◽  
Brennan J. Thompson
Keyword(s):  
Older Adults ◽  
Resistance Training ◽  
Functional Performance ◽  
Functional Decline ◽  
Therapeutic Interventions ◽  
Training Paradigm ◽  
Exercise Participation ◽  
Minimal Dose ◽  
Age Related ◽  
And Function

The ability of older adults to perform activities of daily living is often limited by the ability to generate high mechanical outputs. Therefore, assessing and developing maximal neuromuscular capacity is essential for determining age-related risk for functional decline as well as the effectiveness of therapeutic interventions. Interventions designed to enhance neuromuscular capacities underpinning maximal mechanical outputs could positively impact functional performance in daily life. Unfortunately, < 10% of older adults meet the current resistance training guidelines. It has recently been proposed that a more “minimal dose” RT model may help engage a greater proportion of older adults, so that they may realize the benefits of RT. Eccentric exercise offers some promising qualities for such an approach due to its efficiency in overloading contractions that can induce substantial neuromuscular adaptations. When used in a minimal dose RT paradigm, eccentric-based RT may be a particularly promising approach for older adults that can efficiently improve muscle mass, strength, and functional performance. One approach that may lead to improved neuromuscular function capacities and overall health is through heightened exercise tolerance which would favor greater exercise participation in older adult populations. Therefore, our perspective article will discuss the implications of using a minimal dose, submaximal (i.e., low intensity) multi-joint eccentric resistance training paradigm as a potentially effective, and yet currently underutilized, means to efficiently improve neuromuscular capacities and function for older adults.

scholarly journals Pairing Cholinergic Enhancement with Perceptual Training Promotes Recovery of Age-Related Changes in Rat Primary Auditory Cortex

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Patrice Voss ◽  
Maryse Thomas ◽  
You Chien Chou ◽  
José Miguel Cisneros-Franco ◽  
Lydia Ouellet ◽  
...  
Keyword(s):  
Auditory Cortex ◽  
Structural Changes ◽  
Primary Auditory Cortex ◽  
Auditory Training ◽  
Tone Frequency ◽  
Perceptual Training ◽  
Adult Rats ◽  
Functional Changes ◽  
Age Related ◽  
Old Rats

We used the rat primary auditory cortex (A1) as a model to probe the effects of cholinergic enhancement on perceptual learning and auditory processing mechanisms in both young and old animals. Rats learned to perform a two-tone frequency discrimination task over the course of two weeks, combined with either the administration of a cholinesterase inhibitor or saline. We found that while both age groups learned the task more quickly through cholinergic enhancement, the young did so by improving target detection, whereas the old did so by inhibiting erroneous responses to nontarget stimuli. We also found that cholinergic enhancement led to marked functional and structural changes within A1 in both young and old rats. Importantly, we found that several functional changes observed in the old rats, particularly those relating to the processing and inhibition of nontargets, produced cortical processing features that resembled those of young untrained rats more so than those of older adult rats. Overall, these findings demonstrate that combining auditory training with neuromodulation of the cholinergic system can restore many of the auditory cortical functional deficits observed as a result of normal aging and add to the growing body of evidence demonstrating that many age-related perceptual and neuroplastic changes are reversible.

Sign in / Sign up

Export Citation Format

Share Document