Electroneurographic Evaluation of Neural Impulse Transmission in Patients after Ischemic Stroke Following Functional Electrical Stimulation of Antagonistic Muscles at Wrist and Ankle in Two-Month Follow-Up

The available data from electroneurography (ENG) studies on the transmission of neural impulses in the motor fibers of upper and lower extremity nerves following neuromuscular functional electrical stimulation (NMFES) combined with kinesiotherapy in post-stroke patients during sixty-day observation do not provide convincing results. This study aims to compare the effectiveness of an NMFES of antagonistic muscle groups at the wrist and ankle and kinesiotherapy based mainly on proprioceptive neuromuscular facilitation (PNF). An ENG was performed once in a group of 60 healthy volunteers and three times in 120 patients after stroke (T0, up to 7 days after the incident; T1, after 21 days of treatment; and T2, after 60 days of treatment); 60 subjects received personalized NMFES and PNF treatment (NMFES+K), while the other 60 received only PNF (K). An ENG studied peripheral (M-wave recordings), C8 and L5 ventral root (F-wave recordings) neural impulse transmission in the peroneal and the ulnar nerves on the hemiparetic side. Both groups statistically differed in their amplitudes of M-wave recording parameters after peroneal nerve stimulation performed at T0 and T2 compared with the control group. After 60 days of treatment, only the patients from the NMFES+K group showed significant improvement in M-wave recordings. The application of the proposed NMFES electrostimulation algorithm combined with PNF improved the peripheral neural transmission in peroneal but not ulnar motor nerve fibers in patients after ischemic stroke. Combined kinesiotherapy and safe, personalized, controlled electrotherapy after stroke give better results than kinesiotherapy alone.

Time for Space and the Stability of Prospective Control: Reaching-to-Grasp Gibson

Gibson formulated an approach to goal-directed behavior using prospective information in the context of visually guided locomotion and manual behavior. The former was Gibson's paradigm case, but it is the rapidity of targeted reaching that has provided the special challenge for stable control. Recent treatments of visually guided reaching assume that internal forward models are required to generate stable behavior given delays caused by neural transmission times. Internal models are representations of the sort eschewed by Gibson in favor of prospective information. Reaching is usually described as guided using relative distances of hand and target, but prospective information is usually temporal rather than spatial. We describe proportional rate control models that incorporate time dimensioned prospective information and show they remain stable in the face of delays. The use of time-dimensioned prospective information removes the need for internal models for stable behavior despite neural transmission delays and allows Gibson's approach to prevail.

Surface charge manipulation and electrostatic immobilization of synaptosomes for super-resolution imaging: a study on tau compartmentalization

Synaptosomes are subcellular fractions prepared from brain tissues that are enriched in synaptic terminals, widely used for the study of neural transmission and synaptic dysfunction. Immunofluorescence imaging is increasingly applied to synaptosomes to investigate protein localization. However, conventional methods for imaging synaptosomes over glass coverslips suffer from formaldehyde-induced aggregation. Here, we developed a facile strategy to capture and image synaptosomes without aggregation artefacts. First, ethylene glycol bis(succinimidyl succinate) (EGS) is chosen as the chemical fixative to replace formaldehyde. EGS/glycine treatment makes the zeta potential of synaptosomes more negative. Second, we modified glass coverslips with 3-aminopropyltriethoxysilane (APTES) to impart positive charges. EGS-fixed synaptosomes spontaneously attach to modified glasses via electrostatic attraction while maintaining good dispersion. Individual synaptic terminals are imaged by conventional fluorescence microscopy or by super-resolution techniques such as direct stochastic optical reconstruction microscopy (dSTORM). We examined tau protein by two-color and three-color dSTORM to understand its spatial distribution within mouse cortical synapses, observing tau colocalization with synaptic vesicles as well postsynaptic densities.

Kleptomania Induced by Venlafaxine

Introduction. Kleptomania is an impulse-control disorder that results in an irresistible urge to steal. It is often observed as a comorbidity in patients undergoing pharmacological treatment for Parkinson’s disease. Recurrent shopliftings are also observed in the clinical course of frontotemporal dementia. Case Presentation. After successful treatment of severe depression with venlafaxine at a dose of 225 mg/day, a 54-year-old euthymic female patient exhibited recurrent stealing behavior. After the diagnostic exclusion of frontotemporal dementia, kleptomania induced by venlafaxine administration was suspected. The symptoms of kleptomania disappeared with the gradual decrease in the venlafaxine dosage to 37.5 mg/day. Discussion. Venlafaxine is a dual serotonin-norepinephrine reuptake inhibitor. We considered two possible mechanisms to explain the pathophysiology of kleptomania in the present case: (1) increased dopaminergic neural transmission due to the inhibited dopamine reuptake by the norepinephrine transporter with a high dose of venlafaxine or (2) enhanced serotonergic neural transmission by the inhibition of serotonin reuptake by venlafaxine. In past studies, five cases of impulse-control disorder induced by selective serotonin reuptake inhibitors have been reported. This is the fourth report of venlafaxine-induced kleptomania and highlights the importance of considering the possibility of a rare side effect of kleptomania induced by antidepressant.

Spontaneous neural synchrony links intrinsic spinal sensory and motor networks during unconsciousness

Non-random functional connectivity during unconsciousness is a defining feature of supraspinal networks. However, its generalizability to intrinsic spinal networks remains incompletely understood. Previously, Barry et al. (2014) used fMRI to reveal bilateral resting state functional connectivity within sensory-dominant and, separately, motor-dominant regions of the spinal cord. Here, we record spike trains from large populations of spinal interneurons in vivo in rats and demonstrate that spontaneous functional connectivity also links sensory- and motor-dominant regions during unconsciousness. The spatiotemporal patterns of connectivity could not be explained by latent afferent activity or by populations of interconnected neurons spiking randomly. We also document connection latencies compatible with mono- and di-synaptic interactions and putative excitatory and inhibitory connections. The observed activity is consistent with the hypothesis that salient, experience-dependent patterns of neural transmission introduced during behavior or by injury/disease are reactivated during unconsciousness. Such a spinal replay mechanism could shape circuit-level connectivity and ultimately behavior.

Uncovering the Roles of Clocks and Neural Transmission in the Resilience of Drosophila Circadian Network

Studies of circadian locomotor rhythms in Drosophila melanogaster gave evidence to the preceding theoretical predictions on circadian rhythms. The molecular oscillator in flies, as in virtually all organisms, operates using transcriptional-translational feedback loops together with intricate post-transcriptional processes. Approximately150 pacemaker neurons, each equipped with a molecular oscillator, form a circuit that functions as the central pacemaker for locomotor rhythms. Input and output pathways to and from the pacemaker circuit are dissected to the level of individual neurons. Pacemaker neurons consist of functionally diverse subclasses, including those designated as the Morning/Master (M)-oscillator essential for driving free-running locomotor rhythms in constant darkness and the Evening (E)-oscillator that drives evening activity. However, accumulating evidence challenges this dual-oscillator model for the circadian circuit organization and propose the view that multiple oscillators are coordinated through network interactions. Here we attempt to provide further evidence to the revised model of the circadian network. We demonstrate that the disruption of molecular clocks or neural output of the M-oscillator during adulthood dampens free-running behavior surprisingly slowly, whereas the disruption of both functions results in an immediate arrhythmia. Therefore, clocks and neural communication of the M-oscillator act additively to sustain rhythmic locomotor output. This phenomenon also suggests that M-oscillator can be a pacemaker or a downstream path that passively receives rhythmic inputs from another pacemaker and convey output signals. Our results support the distributed network model and highlight the remarkable resilience of the Drosophila circadian pacemaker circuit, which can alter its topology to maintain locomotor rhythms.

Molecular Characteristics of Amyloid Precursor Protein (APP) and Its Effects in Cancer

Amyloid precursor protein (APP) is a type 1 transmembrane glycoprotein, and its homologs amyloid precursor-like protein 1 (APLP1) and amyloid precursor-like protein 2 (APLP2) are highly conserved in mammals. APP and APLP are known to be intimately involved in the pathogenesis and progression of Alzheimer’s disease and to play important roles in neuronal homeostasis and development and neural transmission. APP and APLP are also expressed in non-neuronal tissues and are overexpressed in cancer cells. Furthermore, research indicates they are involved in several cancers. In this review, we examine the biological characteristics of APP-related family members and their roles in cancer.

Developing Nanodisc-ID for label-free characterizations of membrane proteins

Membrane proteins (MPs) influence all aspects of life, such as tumorigenesis, immune response, and neural transmission. However, characterization of MPs is challenging, as it often needs highly specialized techniques inaccessible to many labs. We herein introduce nanodisc-ID that enables quantitative analysis of membrane proteins using a gel electrophoresis readout. By leveraging the power of nanodiscs and proximity labeling, nanodisc-ID serves both as scaffolds for encasing biochemical reactions and as sensitive reagents for detecting membrane protein-lipid and protein-protein interactions. We demonstrate this label-free and low-cost tool by characterizing a wide range of integral and peripheral membrane proteins from prokaryotes and eukaryotes.