The Genetically Epilepsy-Prone Rat: Neuronal Networks And Actions Of Amino Acid Neurotransmitters
Carl L. Faingold, Gerhard H. Fromm in Drugs for Control of Epilepsy:, 2019
Onset-Offset Responses in Inferior Colliculus Neurons of the GEPR. ICc neurons in the GEPR-9 also show a significantly greater incidence of onset-offset response patterns. This pattern consists of prominent peaks of firing at short latencies from both the beginning and the end of the acoustic stimulus (Figure 2).41 The offset portion of the ICc neuronal response appears predominantly at high stimulus intensities in the GEPR-9 (Figures 2A,B). Since high intensity stimuli are required to trigger AGS, the offset response may represent an afterdischarge similar to that observed in several other seizure models. A form of endogenous inhibition, binaural inhibition, is observed in many ICc neurons when an acoustic stimulus delivered to the ipsilateral ear inhibits the response to a like stimulus delivered simultaneously to the contralateral ear (Figure 3).42 Early studies indicated that this inhibitory pattern is associated with an inhibitory postsynaptic potential.43 The degree of binaurally induced firing inhibition in ICc neurons is significantly less in the GEPR-9 than in normal rats.44 These data indicate that mechanisms underlying inhibition may be defective in the IC of the GEPR-9. The previous data were examined in the paralyzed GEPR-9 that was incapable of exhibiting AGS.
Ion Channels in Human Pluripotent Stem Cells and Their Neural Derivatives
Tian-Le Xu, Long-Jun Wu in Nonclassical Ion Channels in the Nervous System, 2021
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).
Pharmacological MRI as a Molecular Imaging Technique
Michel M. J. Modo, Jeff W. M. Bulte in Molecular and Cellular MR Imaging, 2007
Performing a simple sensory, motor, or cognitive task requires complicated neuronal interactions involving evoking and modulating activity from the molecular to the structural level. For example, finger tapping is the result of coordinating neuronal activity in the ascending sensory and descending motor pathways involving the thalamus, the basal ganglia feedback loop, and sensory, premotor, and motor cortices. The cascading neuronal activity traveling through those functional units reflects a series of neurotransmitter-mediating synaptic transmission and modulation. When a neuronal signal is transmitted at the synapse, it can either evoke or suppress the postsynaptic neuron. For example, glutamate, which induces excitatory postsynaptic potentials (EPSPs), is a major excitatory neurotransmitter in the brain. GABA, which induces inhibitory postsynaptic potentials (IPSPs), is a major inhibitory neurotransmitter. Both glutamate and GABA can be released into the same synapse and alter the function of the postsynaptic neuron competitively. They can also innervate each other to boost (glutamate on GABAergic neuron) or attenuate (GABA on glutamatergic neuron) their ability of releasing the GABA and glutamate neurotransmitters, respectively.
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].
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.
Spider toxins targeting ligand-gated ion channels
Published in Toxin Reviews, 2021
Spider toxins acting on glutamate receptors include acylpolyamines: low molecular weight compounds, present in the venom of many different spiders (Rash and Hodgson 2002, Rogoza et al. 2006). The orb-weaving Joro spider (Nephila clavata) contains a mixture of acylpolyamines. Known as Joro spider toxins (JSTXs), they inhibit glutamate receptors. JSTX-3 is one of the well characterized components among JSTXs; it was shown to be potent at irreversibly inhibiting glutamate-dependent excitatory postsynaptic potential in crustacean neurosmuscular junction without an effect on inhibitory postsynaptic potential (Kawai et al. 1982, Abe et al. 1983). The toxin JSTX-3 was shown to be active at inhibiting mammalian excitatory synapse as well (Kawai et al. 1982, 1984, Saito et al. 1989, Sahara et al. 1991). Subsequent isolation and chemical characterization of toxins from several Nephila spiders revealed a polyamine structure for the toxins (Aramaki et al. 1986). Thus, JSTXs from the Japanese spider Nephila clavata as well as NSTX, a toxin from the New Guinean spider Nephila maculata, have a similar structure containing 2, 4-dihydroxyphenylacetyl-asparaginyl moiety at the head attached via amino-acid linker to the polyamine tail (Aramaki et al. 1986, Shudo et al. 1987). Spiders use a combinatorial approach to increase the diversity of their toxins from a limited set of building blocks (Palma and Nakajima 2005) (Figure 3). The contribution of the linker region and the polyamine tail to the receptor binding was found to be important (Xiong et al. 2014). For example, changing the linker region from asparagine to tert-Leu or tryptophan, decreased selectivity of the JSTX-3 toxin (Abe et al. 1983, Xiong et al. 2014) on AMPA vs. NMDA receptors.
Related Knowledge Centers
- Action Potential
- Chemical Synapse
- Chloride
- Depolarization
- Excitatory Postsynaptic Potential
- Hyperpolarization
- Neurotransmitter Receptor
- Postsynaptic Potential
- Synaptic Potential
- Ligand-Gated Ion Channel