scholarly journals Inhibition Within the Lateral Habenula—Implications for Affective Disorders

2021 ◽  
Vol 15 ◽  
Author(s):  
Jack F. Webster ◽  
Salvatore Lecca ◽  
Christian Wozny

The lateral habenula (LHb) is a key brain region implicated in the pathology of major depressive disorder (MDD). Specifically, excitatory LHb neurons are known to be hyperactive in MDD, thus resulting in a greater excitatory output mainly to downstream inhibitory neurons in the rostromedial tegmental nucleus. This likely results in suppression of downstream dopaminergic ventral tegmental area neurons, therefore, resulting in an overall reduction in reward signalling. In line with this, increasing evidence implicates aberrant inhibitory signalling onto LHb neurons as a co-causative factor in MDD, likely as a result of disinhibition of excitatory neurons. Consistently, growing evidence now suggests that normalising inhibitory signalling within the LHb may be a potential therapeutic strategy for MDD. Despite these recent advances, however, the exact pharmacological and neural circuit mechanisms which control inhibitory signalling within the LHb are still incompletely understood. Thus, in this review article, we aim to provide an up-to-date summary of the current state of knowledge of the mechanisms by which inhibitory signalling is processed within the LHb, with a view of exploring how this may be targeted as a future therapy for MDD.

2021 ◽  
Vol 22 (10) ◽  
pp. 5113
Author(s):  
Jae-Yeon Kim ◽  
Mercedes F. Paredes

A prolonged developmental timeline for GABA (γ-aminobutyric acid)-expressing inhibitory neurons (GABAergic interneurons) is an amplified trait in larger, gyrencephalic animals. In several species, the generation, migration, and maturation of interneurons take place over several months, in some cases persisting after birth. The late integration of GABAergic interneurons occurs in a region-specific pattern, especially during the early postnatal period. These changes can contribute to the formation of functional connectivity and plasticity, especially in the cortical regions responsible for higher cognitive tasks. In this review, we discuss GABAergic interneuron development in the late gestational and postnatal forebrain. We propose the protracted development of interneurons at each stage (neurogenesis, neuronal migration, and network integration), as a mechanism for increased complexity and cognitive flexibility in larger, gyrencephalic brains. This developmental feature of interneurons also provides an avenue for environmental influences to shape neural circuit formation.


Author(s):  
Brendan M. Hickey ◽  
Samuel T. Woo ◽  
Sally F. Shady

Lower limb deficiencies and below knee amputations are the most common form of deficiency that may arise from disease or trauma, and returning a patient close to a normal quality-of-life requires prosthetics, which can be quite challenging. Children present even further difficulty to prosthetists and physicians than adults. Although the underlying prosthetic principles for adults are the same for children, additional considerations must be made for practicality, such as downsizing while maintaining its degree of complexity, and frequent appointments to account for the rapid growth of an adolescent. This review article will evaluate the current state-of-the-art in the field of transtibial-amputee prosthetics, review the insurance coverage a typical family would face, and suggest potential improvements to children’s biomimetic prostheses that aid in reducing the frequency of health care provider intervention.


2019 ◽  
Vol 16 (156) ◽  
pp. 20190259 ◽  
Author(s):  
Xing Gao ◽  
Manon Fraulob ◽  
Guillaume Haïat

In recent decades, cementless implants have been widely used in clinical practice to replace missing organs, to replace damaged or missing bone tissue or to restore joint functionality. However, there remain risks of failure which may have dramatic consequences. The success of an implant depends on its stability, which is determined by the biomechanical properties of the bone–implant interface (BII). The aim of this review article is to provide more insight on the current state of the art concerning the evolution of the biomechanical properties of the BII as a function of the implant's environment. The main characteristics of the BII and the determinants of implant stability are first introduced. Then, the different mechanical methods that have been employed to derive the macroscopic properties of the BII will be described. The experimental multi-modality approaches used to determine the microscopic biomechanical properties of periprosthetic newly formed bone tissue are also reviewed. Eventually, the influence of the implant's properties, in terms of both surface properties and biomaterials, is investigated. A better understanding of the phenomena occurring at the BII will lead to (i) medical devices that help surgeons to determine an implant's stability and (ii) an improvement in the quality of implants.


2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Ploysyne Rattanakaemakorn ◽  
Poonkiat Suchonwanit

Scalp pruritus is a frequent problem encountered in dermatological practice. This disorder is caused by various underlying diseases and is a diagnostic and therapeutic challenge. Scalp pruritus may be localized to the scalp or extended to other body areas. It is sometimes not only associated with skin diseases or specific skin changes, but also associated with lesions secondary to rubbing or scratching. Moreover, scalp pruritus may be difficult to diagnose and manage and may have a great impact on the quality of life of patients. It can be classified as dermatologic, neuropathic, systemic, and psychogenic scalp pruritus based on the potential underlying disease. A thorough evaluation of patients presenting with scalp pruritus is important. Taking history and performing physical examination and further investigations are essential for diagnosis. Therapeutic strategy comprises removal of the aggravating factors and appropriate treatment of the underlying condition. All treatments should be performed considering an individual approach. This review article focuses on the understanding of the pathophysiology and the diagnostic and therapeutic management of scalp pruritus.


2019 ◽  
Vol 80 (02) ◽  
pp. 111-119 ◽  
Author(s):  
Kelsey Dumanch ◽  
Gayla Poling

Objectives To provide an introduction to the role of audiological evaluations with special reference to patients with skull base disease. Design Review article with case-based overview of the current state of the practice of diagnostic audiology through highlighting the multifaceted clinical toolbox and the value of mechanism-based audiological evaluations that contribute to otologic differential diagnosis. Setting Current state of the practice of diagnostic audiology. Main Outcome Measures Understanding of audiological evaluation results in clinical practice and value of contributions to interdisciplinary teams to identify and quantify dysfunction along the auditory pathway and its subsequent effects. Results Accurate auditory information is best captured with a test battery that consists of various assessment crosschecks and mechanism-driven assessments. Conclusion Audiologists utilize a comprehensive clinical toolbox to gather information for assessment, diagnosis, and management of numerous pathologies. This information, in conjunction with thorough medical review, provides mechanism-specific contributions to the otologic and lateral skull base differential diagnosis.


2016 ◽  
Vol 116 (3) ◽  
pp. 1161-1174 ◽  
Author(s):  
P. Leon Brown ◽  
Paul D. Shepard

The lateral habenula, a phylogenetically conserved epithalamic structure, is activated by aversive stimuli and reward omission. Excitatory efferents from the lateral habenula predominately inhibit midbrain dopamine neuronal firing through a disynaptic, feedforward inhibitory mechanism involving the rostromedial tegmental nucleus. However, the lateral habenula also directly targets dopamine neurons within the ventral tegmental area, suggesting that opposing actions may result from increased lateral habenula activity. In the present study, we tested the effect of habenular efferent stimulation on dopamine and nondopamine neurons in the ventral tegmental area of Sprague-Dawley rats using a parasagittal brain slice preparation. Single pulse stimulation of the fasciculus retroflexus excited 48% of dopamine neurons and 51% of nondopamine neurons in the ventral tegmental area of rat pups. These proportions were not altered by excision of the rostromedial tegmental nucleus and were evident in both cortical- and striatal-projecting dopamine neurons. Glutamate receptor antagonists blocked this excitation, and fasciculus retroflexus stimulation elicited evoked excitatory postsynaptic potentials with a nearly constant onset latency, indicative of a monosynaptic, glutamatergic connection. Comparison of responses in rat pups and young adults showed no significant difference in the proportion of neurons excited by fasciculus retroflexus stimulation. Our data indicate that the well-known, indirect inhibitory effect of lateral habenula activation on midbrain dopamine neurons is complemented by a significant, direct excitatory effect. This pathway may contribute to the role of midbrain dopamine neurons in processing aversive stimuli and salience.


2004 ◽  
Vol 19 (4) ◽  
pp. 209-213 ◽  
Author(s):  
Jean-Philippe Boulenger

AbstractResidual symptoms of variable intensity often persist following pharmaco/or psychotherapeutic interventions for treatment of major depression (MD). In several studies, such persistent symptoms have been clearly shown to be associated with a higher risk of relapse, chronicity and functional impairment, but their true nature is still controversial. Several authors consider that these symptoms belong to the range of depression proper and thus indicate that the current episode has been inadequately treated, a hypothesis reinforced by their frequent similarity with the symptoms preceding the full-blown picture of MD. However, in the current state of research, their connection with certain personality traits or comorbid disorders—notably anxiety disorders—cannot be completely ruled out. This article reviews the main data from the literature concerning residual symptoms and their treatment, as well as the issues related to their psychopathological meaning. In practice, once the state of a patient has been stabilized in partial remission of the depressive syndrome, the clinician should revise the current therapeutic strategy and seek to find how to return as fully as possible to the previous euthymic state.


1978 ◽  
Vol 4 (1) ◽  
pp. 62-77 ◽  
Author(s):  
A. J. R. Groom

Any review article has an element of pot luck. An editor receives volumes for review, sorts them into piles according to subject and then thinks of a possible reviewer. The reviewer suggests a few additions and the parameters of the article are set. They are set by what publishers think will sell at a particular time and, more rarely, by what publishers and their academic advisers think ought to be published. A review article is thus frequently about a fashionable topic with a strong emphasis on the current state of conventional wisdom as reflected in the contemporary literature. Terrorism is a topic which fits this bill. It is constantly in the headlines and not surprisingly it has generated some scholarly interest.


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