China
Africa
Explore chapters and articles related to this topic
Ion Channels in Human Pluripotent Stem Cells and Their Neural Derivatives
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
Ritika Raghavan, Robert Juniewicz, Maharaib Syed, Michael Lin, Peng Jiang
Motor neurons have been mainly derived using cell differentiation method that goes through NPC stages. The differentiated cells exhibited motor neuron gene expression, specifically the expression of HB9 and ChAT genes (55–58). The electrophysiological activity of these neurons was tested at both immature and mature stages. At day 5, the cells had weak APs, low spike magnitude and rate, and did not exhibit bursting activity. At day 21, the cells had faster rising spikes, higher spiking frequency, some bursting behavior, and KV- and NaV-mediated currents (55). Calcium imaging studies confirmed the presence of calcium channels along with spontaneous oscillations of intracellular calcium concentrations. Excitatory postsynaptic potentials (EPSPs) were reduced and inhibited in human motor neurons by the application (2R)-amino-5-phosphonovaleric acid; (2R)-amino-5-phosphonopentanoate (D-AP5) and 6-Cyano-2, 3-dihydroxy-7-nitro-quinoxaline (CNQX), indicating the formation of functional excitatory synapses (56). Inhibitory postsynaptic potentials (IPSPs) could be blocked through the application of strychnine and bicuculline, indicating the expression of functional glycine and GABAA receptors in human motor neurons (56). The expression of Acetylcholine (ACh) channels were tested in hPSC-derived motor neurons co-cultured along with C2C12 myocytes. This showed that hPSC motor neurons can form neuromuscular junctions capable of releasing Ach to initiate muscle contraction (58).
Neuronal Function
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Some inhibitory transmitters (e.g. glycine and γ- aminobutyric acid) increase K+ and C1− conductance by causing a local increase in K+ and C1− permeability. The postsynaptic membrane potential becomes hyperpolarized by an increased efflux of K+ ions and influx of C1− ions. As hyperpolarization of the postsynaptic membrane prevents the cell from becoming activated, this is called an inhibitory postsynaptic potential (IPSP).
Interaction of the benzodiazepines with the GABAA receptor
Published in Adam Doble, Ian L Martin, David Nutt, Calming the Brain: Benzodiazepines and related drugs from laboratory to clinic, 2020
Adam Doble, Ian L Martin, David Nutt
GABA-mediated synaptic inhibition, which gives rise to the inhibitory postsynaptic potentials (IPSPs) or currents (IPSCs), has been difficult to study in isolation until recently. At many central synapses these IPSCs result from the exposure of small numbers of GABAA receptors to high or saturating concentrations of GABA for very brief periods as a consequence of vesicular release. Experimentally, this can be adequately mimicked by the brief exposure of small areas of membrane (patches), which contain relatively few GABAA receptors, to high concentrations of GABA. Above, it was suggested that the benzodiazepines effectively shift the GABA con-centration-effect curve to the left but are unable to increase the maximum current. If the amount of GABA released under normal physiological conditions results in saturation of the receptors then the benzodiazepines would be expected to produce no effective facilitation of the GABA-mediated response. However, experimental evidence suggests that zolpidem increases both the amplitude and duration of the synaptic currents (Mody et al, 1994; Hajos et al, 2000). It is argued that the increase in affinity for the agonist GABA, which is caused by the benzodiazepines, results in an increased desensitisation of the receptor (Lavoie and Twyman, 1996), thus shaping the IPSC (Jones and Westbrook, 1995). The benzodiazepines have no direct effect on receptor desensitisation per se (Ghansah and Weiss, 1999).
Assessing the cervico-ocular reflex system via modifying the ocular vestibular-evoked myogenic potential test
Published in International Journal of Neuroscience, 2022
The h-COR responses in Group B were identified in seven patients unilaterally and four patients bilaterally, indicating that unilateral COR is sufficient to alleviate the oscillopsia (Figure 2). How can this finding be interpreted? Uchino et al. [26] reported that the inferior oblique motoneurons developed disynaptic excitatory and inhibitory postsynaptic potentials following stimulation of contralateral anterior semicircular canal and ipsilateral posterior semicircular canal. Although the inferior oblique muscle is optimal site for recording the h-COR, horizontal eye movement, implemented by the medial and lateral rectus muscles, is considered to be more relevant to the oscillopsia. In cases of bilateral VOR loss, head rotation stretches the SCM muscle causing the proprioceptive signals of the SCM muscle activate the Ia spindle afferents to the cervical mid-dorsal root ganglia [27–30]. Subsequently, cervical afferents produce postsynaptic potentials to the vestibular nucleus, and interact with ocular motoneurons from cranial nerves III, IV and VI for conjugating horizontal eye movement and eliciting the h-COR [9, 31]. As ocular motoneurons receive inputs from bilateral cervical afferents [27], it may explain why unilateral COR is sufficient to alleviate oscillopsia.
Stiff-person syndrome: an atypical presentation and a review of the literature
Published in Hospital Practice, 2021
Benjamin C. Lin, Jaspreet Johal, Keithan Sivakumar, Alissa E. Romano, Hussam A. Yacoub
Paraneoplastic SPS is characterized by autoantibodies to amphiphysin, a 128 kDa intracellular protein which enables endocytosis in the synaptic cleft by binding to dynamin to support vesicle budding [49]. In vivo studies have shown that anti-amphiphysin antibodies enter into neurons via an epitope-dependent mechanism [50]. The antibodies preferentially target GABAergic over glutamatergic synapses and binding to these synapses decreases the amplitude of inhibitory postsynaptic potentials [50]. These findings support the pathogenic role of anti-amphiphysin antibodies in paraneoplastic SPS. Further support of the causative link is demonstrated by animal studies showing that truncal and limb stiffness and spasms can be induced in rats following intrathecal or intraperitoneal injection of the antibodies purified from SPS patients with breast cancer, whereas amphiphysin knockout mice did not have any of these symptoms [50,51]. However, as previously stated, only a small proportion of anti-amphiphysin positive patients have SPS and not all SPS cases associated with neoplasm are positive for anti-amphiphysin IgG. One review of 13 patients with paraneoplastic SPS reported only 4 cases positive for anti-amphiphysin IgG [8].
Burst and high frequency stimulation: underlying mechanism of action
Published in Expert Review of Medical Devices, 2018
Shaheen Ahmed, Thomas Yearwood, Dirk De Ridder, Sven Vanneste
On a systemic level, changes in source-localized electroencephalography were analyzed to elucidate the relationships between different frequency bands in tonic and burst stimulation [25]. Significantly more alpha activity was seen in burst stimulation as opposed to tonic stimulation in the dorsal anterior cingulate cortex, the dorsolateral prefrontal cortex, the primary somatosensory cortex, and the posterior cingulate cortex. These findings suggest that burst stimulation has a profound effect on medial, lateral, and descending pathways, whereas tonic stimulation influences the lateral pain pathways [34]. The question remains, however, how burst SCS reaches the brain without – according to animal research – altering the firing rate of the gracile nucleus. The gracile nucleus processes proprioceptive information from the dorsal column such as touch, pressure, and vibration [35]. One hypothesis is that burst SCS modulates the medial pain pathway directly via C-fiber activation, ending in lamina1 connections to the medial thalamic nuclei and anterior cingulate cortex. Another existing question is regarding the mechanism by which burst stimulation suppresses pain. One possible answer to this question is that burst stimulation disrupts synchronous firing of the high-threshold C-fibers related to pain perception [36–38]. This could be caused by reducing synchrony or generating inhibitory postsynaptic potentials which are maximal at 500-Hz bursts [39]. Another possibility is that burst SCS exerts its pain-improving effects by activating the antinociceptive low-threshold tactile C-fibers.