scholarly journals Polarity of varicosity initiation in central neuron mechanosensation

2017 ◽  
Vol 216 (7) ◽  
pp. 2179-2199 ◽  
Author(s):  
Yuanzheng Gu ◽  
Peter Jukkola ◽  
Qian Wang ◽  
Thomas Esparza ◽  
Yi Zhao ◽  
...  

Little is known about mechanical regulation of morphological and functional polarity of central neurons. In this study, we report that mechanical stress specifically induces varicosities in the axons but not the dendrites of central neurons by activating TRPV4, a Ca2+/Na+-permeable mechanosensitive channel. This process is unexpectedly rapid and reversible, consistent with the formation of axonal varicosities in vivo induced by mechanical impact in a mouse model of mild traumatic brain injury. In contrast, prolonged stimulation of glutamate receptors induces varicosities in dendrites but not in axons. We further show that axonal varicosities are induced by persistent Ca2+ increase, disassembled microtubules (MTs), and subsequently reversible disruption of axonal transport, and are regulated by stable tubulin-only polypeptide, an MT-associated protein. Finally, axonal varicosity initiation can trigger action potentials to antidromically propagate to the soma in retrograde signaling. Therefore, our study demonstrates a new feature of neuronal polarity: axons and dendrites preferentially respond to physical and chemical stresses, respectively.

1990 ◽  
Vol 63 (4) ◽  
pp. 651-662 ◽  
Author(s):  
P. Calabresi ◽  
N. B. Mercuri ◽  
A. Stefani ◽  
G. Bernardi

1. The relationship between membrane properties of neostriatal neurons and spontaneous and evoked synaptic potentials was studied with the use of intracellular recordings from anesthetized rats. Most of these neurons showed regular or irregular spontaneous depolarizing potentials that only in a few cases triggered action potentials at resting level. 2. The stimulation of the ipsilateral substantia nigra or of the sensorimotor cortex produced a relatively fast depolarizing post-synaptic potential (EPSP). In some cells this potential was followed by an inhibitory period that appeared as an hyperpolarization when the cell was depolarized from the resting level (inhibitory postsynaptic potential, IPSP). A late and long-lasting depolarization (LD) followed the EPSP or the EPSP-IPSP sequence. 3. Repetitive discharge with little adaptation was observed during direct depolarization. Most of the neurons tested for current-voltage (I-V) relationship showed nonlinearity of the input resistance in the hyperpolarizing direction. Spontaneous and evoked EPSPs were decreased in their amplitude and duration when the membrane potential was held at levels more hyperpolarized than -85 mV because of the strong rectification at these levels of hyperpolarization. 4. Local microiontophoretic application of bicuculline (BIC) or systemic administration of BIC and pentylenetetrazole (PTZ) produced a reduction of the IPSPs. The reduction of the inhibitory transmission caused a strong increase of the LD. The current-evoked firing pattern was not greatly altered. 5. The intracellular application of cesium increased the amplitude and the duration of the spontaneous depolarizations that triggered bursts of action potentials under this condition. Spikes were broadened and the rectification in the hyperpolarization direction was reduced. 6. Iontophoretically applied cadmium strongly depressed the amplitude of the spontaneous and evoked postsynaptic potentials. During cadmium application, nigral stimulation produced constant latency, all-or-none spikes in the absence of any synaptic potential. 7. Repetitive stimulation of the ipsilateral substantia nigra by electrical shocks (5 Hz, 25 s) produced a progressive and reversible decrease of the spontaneous depolarizing potentials (SDPs) and a decrease of the firing rate. In the same cells, when the train of stimulation was delivered in the ipsilateral cortex, a membrane depolarization coupled with an increase of the firing rate was observed. 8. We conclude that although synaptic circuits mediate a phasic inhibition in neostriatum, the low level of spontaneous firing of most neostriatal neurons is mainly because of the effects that membrane properties exert on the spontaneous and the evoked synaptic depolarizations in the striatum.(ABSTRACT TRUNCATED AT 400 WORDS)


1993 ◽  
Vol 69 (6) ◽  
pp. 1850-1864 ◽  
Author(s):  
A. Baranyi ◽  
M. B. Szente ◽  
C. D. Woody

1. Patterns of firing activity and characteristics of antidromic and synaptic responses to stimulation of the pyramidal tract at peduncular level [peduncular pyramidal tract (PP)] and the ventrolateral thalamic nucleus (VL) were studied in neurons of area 4 gamma of the motor cortex of awake, chronic cats using intracellular microelectrode techniques. The results offer a new functional classification of neocortical neurons based on electrophysiological properties of the 640 recorded cells. 2. Four classes of neurons were distinguished: (class i) inactivating bursting (ib) neurons (n = 60) including fast antidromic response PP (fPP) (n = 0), slow antidromic response PP (sPP) (n = 11), and no antidromic response PP cells (nPP) (n = 49); (class ii) noninactivating bursting (nib) neurons (n = 79), including fPP (n = 23), sPP (n = 0), and nPP cells (n = 56); (class iii) fast-spiking (fsp) neurons (n = 56), including fPP (n = 0), sPP (n = 0), and nPP cells (n = 56); and (class iv) regular-spiking (rsp) neurons (n = 445), including fPP (n = 96), sPP (n = 38), and nPP cells (n = 311). (Neurons in each classification were further separated by their antidromic responses to PP stimulation: fast PP (fPP) slow PP (sPP), or nPP cells, the latter not responding antidromically to electrical stimulation of the peduncle.) 3. Recurrent monosynaptic excitatory postsynaptic potentials (EPSPs) followed antidromic spikes elicited by PP stimulation in most (96%) fPP but much fewer (24%) sPP cells. In fPP cells, it was possible to separate the PP EPSPs into two monosynaptic EPSP components that were generated by other fPP and sPP cells, respectively. VL stimulation evoked monosynaptic EPSPs in 100% of fPP cells (vs. 63% of sPP cells) and antidromic action potentials in 16% of fPP cells (vs. 12% of sPP cells). 4. Firing activity consisted of single spike discharges in most PP cells; however, noninactivating bursting was observed in 19% of fPP cells, and inactivating bursting was observed in 23% of sPP cells (see below). In 18% of ib and 11% of nib/nPP neurons, VL stimulation elicited antidromic action potentials. Other bursting neurons proved to be PP cells with characteristic differences in axonal conduction velocity (see above). All PP cells among the nib cells were fPP, and all PP cells among the ib cells were sPP cells. All fsp neurons were found to be nPP cells, and none could be activated antidromically by VL stimulation. Thus the fsp pattern of discharge distinguished a unique class of nPP cells.(ABSTRACT TRUNCATED AT 400 WORDS)


1982 ◽  
Vol 242 (3) ◽  
pp. R237-R243
Author(s):  
Z. J. Bosnjak ◽  
J. L. Seagard ◽  
J. P. Kampine

In vitro and in vivo studies were conducted on the stellate ganglion (SG) of the dog by recording action potentials from its nerves and its neurons. For in vitro preparations, the SG and its nerve trunks were dissected from the animal and secured in an organ bath. Peripheral input to the SG was produced by electrical stimulation of the ventral ansa subclavia (VA), dorsal ansa subclavia (DA), and stellate cardiac nerve (SC) in 15 ganglion preparations studied in vitro. Electrical stimulation of the VA elicited action potentials recorded at the DA. This conducting pathway did not involve direct anatomic continuity, since the evoked potentials were blocked by injection of hexamethonium chloride into the SG. Most neurons in the SG received synaptic input from fibers of both central and peripheral origin. In 12 in vivo preparations, all nerves to the SG except the VA were cut. When peripheral sympathetic afferent input to the SG was increased, some of the postganglionic fibers of the dissected DA exhibited an increase in efferent nerve discharge. This response was also blocked by hexamethonium chloride. These results indicate that some of the functions of the SG might be independent of the central nervous system.


2001 ◽  
Vol 86 (2) ◽  
pp. 616-628 ◽  
Author(s):  
Valerie K. Haftel ◽  
Jonathan F. Prather ◽  
C. J. Heckman ◽  
Timothy C. Cope

This study provides the first test in vivo of the hypothesis that group Ia muscle-stretch afferents aid in preventing reversals in the orderly recruitment of motoneurons. This hypothesis was tested by studying recruitment of motoneurons deprived of homonymous afferent input. Recruitment order was measured in decerebrate, paralyzed cats from dual intra-axonal records obtained simultaneously from pairs of medial gastrocnemius (MG) motoneurons. Pairs of MG motor axons were recruited in eight separate trials of the reflex discharge evoked by stimulation of the caudal cutaneous sural (CCS) nerve. Some reports suggest that reflex recruitment by this cutaneous input should bias recruitment against order by the size principle in which the axon with the slower conduction velocity (CV) in a pair is recruited to fire before the faster CV axon. Recruitment was studied in three groups of cats: ones with the MG nerve intact and untreated (UNTREATED); ones with the MG nerve cut (CUT); and ones with the MG nerve cut and bathed at its proximal end in lidocaine solution (CUT+). The failure of electrical stimulation to initiate a dorsal root volley and the absence of action potentials in MG afferents demonstrated the effective elimination of afferent feedback in the CUT+ group. Recruitment order by the size principle predominated and was not statistically distinguishable among the three groups. The percentage of pairs recruited in reverse order of the size principle was actually smaller in the CUT+ group (6%) than in CUT (15%) or UNTREATED (19%) groups. Thus homonymous afferent feedback is not necessary to prevent recruitment reversal. However, removing homonymous afferent input did result in the expression of inconsistency in order, i.e., switches in recruitment sequence from one trial to the next, for more axon pairs in the CUT+ group (33%) than for the other groups combined (13%). Increased inconsistency in the absence of increased reversal of recruitment order was approximated in computer simulations by increasing time-varying fluctuations in synaptic drive to motoneurons and could not be reproduced simply by deleting synaptic current from group Ia homonymous afferents, regardless of how that current was distributed to the motoneurons. These findings reject the hypothesis that synaptic input from homonymous group Ia afferents is necessary to prevent recruitment reversals, and they are consistent with the assertion that recruitment order is established predominantly by properties intrinsic to motoneurons.


1988 ◽  
Vol 117 (4_Suppl) ◽  
pp. S199-S200
Author(s):  
E. DIETRICH ◽  
K. RENTELMANN ◽  
W. WUTTKE

2008 ◽  
Author(s):  
Nichole M. Jindra ◽  
Robert J. Thomas ◽  
Douglas N. Goddard ◽  
Michelle L. Imholte

Diabetes ◽  
2007 ◽  
Vol 56 (4) ◽  
pp. 1087-1094 ◽  
Author(s):  
M. G. Latour ◽  
T. Alquier ◽  
E. Oseid ◽  
C. Tremblay ◽  
T. L. Jetton ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Celinda M. Kofron ◽  
Tae Yun Kim ◽  
Fabiola Munarin ◽  
Arvin H. Soepriatna ◽  
Rajeev J. Kant ◽  
...  

AbstractCardiotoxicity of pharmaceutical drugs, industrial chemicals, and environmental toxicants can be severe, even life threatening, which necessitates a thorough evaluation of the human response to chemical compounds. Predicting risks for arrhythmia and sudden cardiac death accurately is critical for defining safety profiles. Currently available approaches have limitations including a focus on single select ion channels, the use of non-human species in vitro and in vivo, and limited direct physiological translation. We have advanced the robustness and reproducibility of in vitro platforms for assessing pro-arrhythmic cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts in 3-dimensional microtissues. Using automated algorithms and statistical analyses of eight comprehensive evaluation metrics of cardiac action potentials, we demonstrate that tissue-engineered human cardiac microtissues respond appropriately to physiological stimuli and effectively differentiate between high-risk and low-risk compounds exhibiting blockade of the hERG channel (E4031 and ranolazine, respectively). Further, we show that the environmental endocrine disrupting chemical bisphenol-A (BPA) causes acute and sensitive disruption of human action potentials in the nanomolar range. Thus, this novel human 3D in vitro pro-arrhythmic risk assessment platform addresses critical needs in cardiotoxicity testing for both environmental and pharmaceutical compounds and can be leveraged to establish safe human exposure levels.


1984 ◽  
Vol 62 (1) ◽  
pp. 153-156 ◽  
Author(s):  
Archana Chaudhry ◽  
John W. Downie ◽  
Thomas D. White

The present study was carried out to assess the possible role of ATP in the noncholinergic, nonadrenergic transmission in the rabbit urinary bladder. When rabbit detrusor muscle strips were superfused with medium containing firefly luciferin–luciferase and stimulated transmurally at low stimulation parameters, tetrodotoxin-sensitive contractions were obtained but no release of ATP could be detected. However, at somewhat higher stimulation parameters, release of ATP was observed. This release of ATP was not diminished by tetrodotoxin indicating that ATP was not likely released as a result of propagated action potentials in nerves. Because contractions persisted in the presence of tetrodotoxin, it is possible that the ATP might have been released as a result of direct electrical stimulation of the muscle. These results do not support the idea that ATP is released as a neurotransmitter in the rabbit bladder.


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