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Endogenous regulators of G protein signaling proteins regulate presynaptic inhibition at rat hippocampal synapses

Chen, Huanmian; Lambert, Nevin A.
Fonte: The National Academy of Sciences Publicador: The National Academy of Sciences
Tipo: Artigo de Revista Científica
EN
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46.56%
Presynaptic inhibition mediated by G protein-coupled receptors (GPCRs) can develop and decay in a few seconds. This time course is too rapid to be accounted for by the intrinsic GTPase activity of Gα subunits alone. Here, we test the hypothesis that endogenous regulators of G protein signaling (RGS proteins) are required for rapid, brief presynaptic inhibition. Endogenous G protein α subunits were uncoupled from GPCRs by treating cultures with pertussis toxin (PTX). Adenoviral expression of mutant PTX-insensitive (PTX-i) Gαi1–3 or Gαo subunits rescued adenosine-induced presynaptic inhibition in cultured hippocampal neurons. Expression of double mutant Gαi1 or Gαo subunits that were both PTX-insensitive and unable to bind RGS proteins (PTX/RGS-i) also rescued presynaptic inhibition. Presynaptic inhibition mediated by PTX/RGS-i subunits decayed much more slowly after agonist removal than that mediated by PTX-i subunits or native G proteins. The onset of presynaptic inhibition mediated by PTX/RGS-i Gαo was also slower than that mediated by PTX-i Gαo. In contrast, the onset of presynaptic inhibition mediated by PTX/RGS-i Gαi1 was similar to that mediated by PTX-i Gαi1. These results suggest that endogenous RGS proteins regulate the time course of G protein signaling in mammalian central nervous system presynaptic terminals.

Tail shock produces inhibition as well as sensitization of the siphon-withdrawal reflex of Aplysia: possible behavioral role for presynaptic inhibition mediated by the peptide Phe-Met-Arg-Phe-NH2.

Mackey, S L; Glanzman, D L; Small, S A; Dyke, A M; Kandel, E R; Hawkins, R D
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/1987 EN
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46.53%
Recent studies have shown that, in addition to being modulated by presynaptic facilitation, the sensory neurons of the gill- and siphon-withdrawal reflex of Aplysia are also capable of being modulated by transient presynaptic inhibition produced by the peptide Phe-Met-Arg-Phe-NH2. These two modulatory effects involve different second-messenger systems: the facilitation is mediated through cAMP-dependent protein phosphorylation, and the inhibition is mediated through the lipoxygenase pathway of arachidonic acid. To explore the behavioral function of this inhibition, we have carried out a parametric analysis of the effect of tail shock on the siphon-withdrawal reflex. In addition to producing sensitization of the withdrawal reflex, tail shock also transiently inhibits the reflex. The inhibition is produced by relatively weak shock, whereas sensitization is more prominent and may mask the inhibition with stronger shock. Furthermore, inhibition is not observed after habituation training. Cellular studies suggest that the behavioral inhibition is mediated, at least in part, by presynaptic inhibition of transmitter release from the siphon sensory neurons. Moreover, we have identified an interneuron within the left pleural ganglion (LPL16) that shows Phe-Met-Arg-Phe-NH2 immunoreactivity...

Presynaptic inhibition in Aplysia involves a decrease in the Ca2+ current of the presynaptic neuron.

Shapiro, E; Castellucci, V F; Kandel, E R
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1980 EN
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46.54%
By voltage clamping presynaptic cell L10 and using pharmacologic separation techniques, we have analyzed the specific ionic currents in the presynaptic cell that correlate with presynaptic inhibition while assaying transmitter release with intracellular recordings from postsynaptic cells. We have found that presynaptic inhibition can be elicited in conditions in which the Na+ and the various K+ channels are pharmacologically blocked and depolarizing current pulses produce only an inward Ca2+ current. Both inward currents and tail currents at and above the K+ reversal potential were always less inward during presynaptic inhibition. The changes in conductance associated with presynaptic inhibition were voltage sensitive and paralleled the voltage sensitivity of the Ca2+ channel. We therefore conclude that presynaptic inhibition is caused by a direct transmitter-mediated decreased of presynaptic Ca2+-channel conductance.

Is presynaptic inhibition distributed to corticospinal fibres in man?

Nielsen, J; Petersen, N
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/05/1994 EN
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46.56%
1. A tendon tap of the biceps femoris tendon was found to evoke a depression of the soleus and tibialis anterior H reflexes with a duration of 300-400 ms and with an onset at a conditioning-test interval of 20-30 ms. It is suggested that the depression is caused by presynaptic inhibition of the terminals of the Ia afferents mediating the reflexes. 2. This possibility was tested by a method in which the H reflex is facilitated by a monosynaptic Ia volley from the quadriceps muscle. The attenuation of this facilitation when another pathway is stimulated is probably caused by presynaptic inhibition of Ia afferents. It was shown that the biceps femoris tendon tap depressed the size of the femoral nerve-induced facilitation of the soleus and tibialis anterior H reflexes. This suggests that the depression of the reflexes by the tendon tap was indeed caused by presynaptic inhibition. 3. To investigate whether the terminals of descending fibres were similarly susceptible to presynaptic inhibition, the stimulation of the femoral nerve was replaced by magnetic stimulation of the contralateral motor cortex. This stimulation has been shown to evoke a facilitation of the tibialis anterior and soleus H reflexes which (within its initial 0.5-1 ms) is probably caused exclusively by direct monosynaptic projections from the cortex to the motoneurones. In contrast to the facilitation evoked by Ia afferents...

GABAB receptor-mediated presynaptic inhibition in guinea-pig hippocampus is caused by reduction of presynaptic Ca2+ influx.

Wu, L G; Saggau, P
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/06/1995 EN
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46.52%
1. The hypothesis that activation of GABAB receptors inhibits evoked synaptic transmission by reducing the presynaptic Ca2+ influx was tested using a recently developed technique for simultaneously recording the presynaptic Ca2+ transient ([Ca2+]t) and the field excitatory postsynaptic potential (fEPSP) evoked by a single electrical stimulus at CA3 to CA1 synapses of guinea-pig hippocampus. 2. The GABAB receptor agonist baclofen reversibly blocked, in a dose-dependant manner, both the fEPSP and the presynaptic [Ca2+]t with similar time courses. During application of baclofen, the fEPSP was proportional to about the fourth power of the presynaptic [Ca2+]t, and the presynaptic fibre volley and the resting Ca2+ level did not change. These results are similar to those we previously observed following application of several voltage-dependent Ca2+ channel blockers, suggesting that baclofen inhibits the fEPSP by blocking the presynaptic Ca2+ influx. 3. The inhibition by baclofen of both the fEPSP and the presynaptic [Ca2+]t was blocked by the GABAB receptor antagonist CGP 35348, consistent with the causal relationship between the GABAB receptor-mediated presynaptic inhibition of the [Ca2+]t and the fEPSP. 4. The inhibition by baclofen of the [Ca2+]t was partially occluded by application of the voltage-dependent Ca2+ channel blocker omega-conotoxin-GVIA (omega-CgTX-GVIA)...

Evidence for cutaneous and corticospinal modulation of presynaptic inhibition of Ia afferents from the human lower limb.

Iles, J F
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/02/1996 EN
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46.56%
1. Presynaptic inhibition of soleus muscle Ia afferent fibres, produced by stimulation of group I afferents in the common peroneal nerve, was assessed from changes in the H reflex at long conditioning intervals, in six normal subjects. 2. Stimulation of the ipsilateral sural nerve at the malleolus, just before stimulation of the common peroneal nerve at the head of the fibula, decreased the presynaptic inhibition. This effect was strongest during voluntary plantar flexion and weaker during dorsiflexion or at rest. 3. Stimulation of other cutaneous nerve branches serving the dorsum of the ipsilateral foot, and also the contralateral sural nerve, decreased presynaptic inhibition. Adequate stimulation of low threshold cutaneous mechanoreceptors by light brushing of both distal dorsal and plantar surfaces of the ipsilateral foot decreased presynaptic inhibition. 4. Stimulation of the ipsilateral plantar nerves increased presynaptic inhibition, but this action is attributed to activation of group I afferents from the intrinsic muscles of the foot. 5. Transcranial magnetic stimulation of the lower limb area of the contralateral motor cortex decreased presynaptic inhibition. This effect was strongest during voluntary plantar flexion and weaker during dorsiflexion or at rest. 6. The actions of cutaneous and corticospinal pathways completely occluded each other. However...

The role of GABAA and GABAB receptors in presynaptic inhibition of Ia EPSPs in cat spinal motoneurones.

Stuart, G J; Redman, S J
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1992 EN
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46.54%
1. The role of GABAA and GABAB receptors in presynaptic inhibition was studied by examining the effect of local application of antagonists by ionophoresis during intracellular recording of presynaptic inhibition of compound and unitary group Ia afferent excitatory postsynaptic potentials (EPSPs) in gastrocnemius motoneurones. 2. Ionophoresis of the GABAA antagonist bicuculline methochloride (BMC) was found to block presynaptic inhibition of both compound and unitary EPSPs by up to 85%. BMC also substantially reduced, and occasionally abolished, the late part of the inhibitory postsynaptic potential (IPSP) evoked in motoneurones by the conditioning stimulation. The early part of this IPSP was found to be sensitive to ionophoresis of strychnine hydrochloride. 3. Ionophoresis of 2-OH-saclofen caused a reduction in presynaptic inhibition of compound EPSPs by 5-25% but had no effect on the IPSP evoked in motoneurones by the conditioning stimulation. 4. Ionophoresis of the GABAB antagonist (-)-baclofen reduced the amplitude of unconditioned EPSPs; however it had little effect on presynaptic inhibition. 5. It was concluded that at the Ia afferent-motoneurone synapse presynaptic inhibition is mediated primarily through the activation of GABAA receptors. The activation of GABAB receptors appears to play only a minor role in presynaptic inhibition at this synapse. This contrasts with the relative ease with which (-)-baclofen can reduce transmitter release from Ia afferent terminals and suggests that the receptors activated by (-)-baclofen are predominantly extrasynaptic.

Cutaneous effects on presynaptic inhibition of flexor Ia afferents in the human forearm.

Nakashima, K; Rothwell, J C; Day, B L; Thompson, P D; Marsden, C D
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/1990 EN
Relevância na Pesquisa
46.5%
1. In six subjects, H reflexes obtained in the flexor muscles in the forearm were inhibited by single motor threshold shocks to the radial nerve in the spiral groove. The first two phases of the inhibitory time course were studied: with intervals between the radial and median nerve shocks of -1 to +1 ms, and +5 to +30 ms. These two phases are thought to be due respectively to disynaptic inhibition between radial Ia afferents and flexor alpha-motoneurones, and to presynaptic inhibition of flexor Ia afferents. 2. Single or short trains (10 ms, 400 Hz) of cutaneous stimuli to the dorsal or palmar aspect of the proximal phalanx of the index finger or to the superficial radial nerve at the wrist, reduced the amount of presynaptic inhibition by 10-20%, but had no effect on the earlier disynaptic inhibition. Single stimuli to either side of the index finger or trains of stimuli to the ventral side, had no effect on the size of control H reflexes elicited alone. 3. Effects of cutaneous nerve shocks on presynaptic inhibition could be seen with stimuli as small as 1.5 x perceptual threshold. 4. Anaesthesia of the hand in one subject reversibly increased the amount of presynaptic inhibition and decreased the amount of disynaptic inhibition. 5. We conclude that...

Assessing changes in presynaptic inhibition of I a fibres: a study in man and the cat.

Hultborn, H; Meunier, S; Morin, C; Pierrot-Deseilligny, E
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1987 EN
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46.56%
1. A method to assess changes in presynaptic inhibition of I a afferent terminals in man is proposed. The soleus H reflex was facilitated by a heteronymous I a volley from quadriceps and the amount of reflex facilitation was used to estimate the size of the conditioning I a excitatory post-synaptic potential (e.p.s.p.). It is argued that the size of this e.p.s.p. as measured by the resulting amount of reflex facilitation reflects the amount of presynaptic inhibition on the corresponding I a fibres. A decrease in the reflex facilitation may then be ascribed to an increase in presynaptic inhibition of the I a fibres mediating the conditioning volley. 2. That the heteronymous I a facilitation from quadriceps to soleus is caused by a purely monosynaptic e.p.s.p. is a prerequisite for the validity of the method. Experimental evidence is therefore given in an Appendix that in man the earliest part (first 0.5 ms) of this heteronymous I a facilitation is mediated through a monosynaptic pathway. Evidence is also given that this earliest facilitation is not yet contaminated by any polysynaptic effects from I a or I b afferents. 3. The validity of the method was established in animal experiments in which presynaptic inhibition of I a fibres and post-synaptic events in motoneurones could be assessed by direct tests. It was found that the amount of test reflex facilitation produced by a conditioning I a volley was decreased when I a fibres were subjected to presynaptic inhibition but remained unchanged when the motoneurone pool in which the test reflex was elicited received pure post-synaptic inhibition. 4. In man...

Changes in presynaptic inhibition of Ia fibres at the onset of voluntary contraction in man.

Hultborn, H; Meunier, S; Pierrot-Deseilligny, E; Shindo, M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1987 EN
Relevância na Pesquisa
46.61%
1. Two independent methods were used, in man, to assess changes in presynaptic inhibition of I a terminals at the onset of selective voluntary contractions: (1) measurement of the amount of heteronymous monosynaptic I a facilitation (from the quadriceps muscle to soleus motoneurones) to provide an assessment of the amount of ongoing presynaptic inhibition exerted on the I a fibres responsible for the facilitation; (2) measurement of the inhibition of H reflexes 40-60 ms after a short vibration to the tibialis anterior tendon to estimate the excitability of the interneurones mediating presynaptic inhibition from tibialis anterior I a afferents to the I a afferents of the test H reflex (soleus or quadriceps). 2. At the onset of an isolated voluntary plantar flexion of the foot (gastrocnemius-soleus contraction) the heteronymous facilitation from quadriceps to soleus was increased, reflecting a decreased presynaptic inhibition of the quadriceps I a terminals on soleus motoneurones. Vibratory inhibition of the soleus H reflex was decreased, reflecting an inhibition of transmission of presynaptic inhibition to homonymous soleus I a afferent terminals. 3. At the onset of the same gastrocnemius-soleus contraction there was, on the contrary...

4-Aminopyridine and low Ca2+ differentiate presynaptic inhibition mediated by neuropeptide Y, baclofen and 2-chloroadenosine in rat hippocampal CA1 in vitro.

Klapstein, G. J.; Colmers, W. F.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1992 EN
Relevância na Pesquisa
46.5%
1. Presynaptic inhibition is mediated by several receptors at the stratum radiatum-CA1 synapse of rat hippocampus. We tested whether the same mechanism is activated by neuropeptide Y (NPY), baclofen and 2-chloroadenosine (2-CA), reasoning that if the receptors all activated the same process, then they should all respond to indirect manipulations of transmitter release in the same manner. 2. The effects on presynaptic inhibition by the potassium channel blocker, 4-aminopyridine (4-AP) and low extracellular concentrations of Ca2+ in the presence of 4-AP were compared using evoked population excitatory postsynaptic potentials (p.e.p.s.p.) responses in the rat hippocampal slice in vitro. 3. Log concentration-effect relationships for the inhibition of excitatory transmission were constructed for all 3 drugs in normal saline, and in the presence of 30 and 100 microM 4-AP. 4-AP reduced the inhibition mediated by all three substances, 100 microM 4-AP was only slightly more effective than 30 microM. 4. Lowering extracellular Ca2+ from 1.5 to 0.75 mM in the presence of 30 microM 4-AP restored the presynaptic inhibition caused by all effective concentrations of NPY and baclofen. By contrast, inhibition caused by 2-CA was not restored by lowering Ca2+...

Mechanical cutaneous stimulation alters Ia presynaptic inhibition in human wrist extensor muscles: a single motor unit study

Aimonetti, Jean-Marc; Vedel, Jean-Pierre; Schmied, Annie; Pagni, Simone
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em 01/01/2000 EN
Relevância na Pesquisa
46.54%
Reflex responses were evoked by radial nerve stimulation in 25 single motor units in the extensor carpi radialis muscles of seven subjects during voluntary isometric wrist extension. The responses consisted of narrow peaks in the post-stimulus time histograms with latencies compatible with monosynaptic activation.When the skin of the palm and finger tips was continuously swept using a soft rotating brush, the purely monosynaptic components of the motor unit responses, as assessed from the contents of the first two 0.25 ms bins of the peak, were found to increase. This increase did not affect the motoneurone net excitatory drive, as assessed by measuring the mean duration of the inter-spike intervals. The cutaneous inputs activated by the brush may have reduced the tonic presynaptic inhibition exerted on the Ia afferents homonymous to the extensor motor units tested.To further investigate whether Ia presynaptic inhibition was involved, the responses of the extensor motor units were conditioned by stimulating the median nerve 20 ms earlier, using a protocol which is known to induce Ia extensor presynaptic inhibition originating from flexor Ia afferents. The median nerve stimulation did not affect the motoneurone excitatory drive, but led to a decrease in the responses of the extensor motor units to the radial nerve stimulation...

In vivo modulation of sensory input to the olfactory bulb by tonic and activity-dependent presynaptic inhibition of receptor neurons

Pírez, Nicolás; Wachowiak, Matt
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 18/06/2008 EN
Relevância na Pesquisa
46.5%
The first reorganization of odor representations in the nervous system occurs at the synapse between olfactory receptor neurons and second-order neurons in olfactory bulb glomeruli. Signal transmission at this synapse is modulated presynaptically by several mechanisms, a major one being mediated by GABAB receptors, which suppress presynaptic calcium influx and subsequent transmitter release from the receptor neuron terminal. Here, we imaged stimulus-evoked calcium influx into the receptor neuron terminal in anesthetized mice, and used odorant and electrical stimulation combined with in vivo pharmacology to characterize the functional determinants of GABAB-mediated presynaptic inhibition and to test hypotheses on the role of this inhibition in olfactory processing. As expected from earlier studies, blocking presynaptic GABAB receptors in vivo increased odorant-evoked presynaptic calcium signals, confirming that GABAB-mediated inhibition modulates the strength of receptor inputs. Surprisingly, we found that the strength of this inhibition was affected little by the nature of the input, being independent of the spatial distribution of activated glomeruli, independent of the sniff frequency used to sample the odorant, and similar for weak and strong odorant-evoked inputs. Instead...

GABAB Receptor-Mediated Presynaptic Inhibition Has History-Dependent Effects on Synaptic Transmission during Physiologically Relevant Spike Trains

Ohliger-Frerking, Patricia; Wiebe, Sherman P.; Stäubli, Ursula; Frerking, Matthew
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/06/2003 EN
Relevância na Pesquisa
46.52%
Presynaptic inhibition is a form of neuromodulation that interacts with activity-dependent short-term plasticity so that the magnitude, and sometimes even the polarity, of that activity-dependent short-term plasticity is changed. However, the functional consequences of this interaction during physiologically relevant spike trains are poorly understood. We examined the effects of presynaptic inhibition on excitatory synaptic transmission during physiologically relevant spike trains, using the GABAB receptor (GABABR) agonist baclofen to engage presynaptic inhibition and field EPSPs (fEPSPs) in hippocampal slices to monitor synaptic output. We examined the effects of baclofen on the relationship between an fEPSP during the spike train and the timing of spikes preceding that fEPSP, a relationship that we refer to as the history dependence of synaptic transmission. Baclofen alters this history dependence by causing no inhibition during short interspike intervals (ISIs) in the spike train but a maximal inhibition during long ISIs. This effect strengthens the dependence of the fEPSP on the first ISI preceding it. One consequence of this effect is that the apparent affinity of baclofen is strongly reduced during physiologically relevant spike trains when compared with conventional stimulus paradigms...

Stance-phase force on the opposite limb dictates swing-phase afferent presynaptic inhibition during locomotion

Hayes, Heather Brant; Chang, Young-Hui; Hochman, Shawn
Fonte: American Physiological Society Publicador: American Physiological Society
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
46.51%
Presynaptic inhibition is a powerful mechanism for selectively and dynamically gating sensory inputs entering the spinal cord. We investigated how hindlimb mechanics influence presynaptic inhibition during locomotion using pioneering approaches in an in vitro spinal cord–hindlimb preparation. We recorded lumbar dorsal root potentials to measure primary afferent depolarization-mediated presynaptic inhibition and compared their dependence on hindlimb endpoint forces, motor output, and joint kinematics. We found that stance-phase force on the opposite limb, particularly at toe contact, strongly influenced the magnitude and timing of afferent presynaptic inhibition in the swinging limb. Presynaptic inhibition increased in proportion to opposite limb force, as well as locomotor frequency. This form of presynaptic inhibition binds the sensorimotor states of the two limbs, adjusting sensory inflow to the swing limb based on forces generated by the stance limb. Functionally, it may serve to adjust swing-phase sensory transmission based on locomotor task, speed, and step-to-step environmental perturbations.

AMPA receptor-mediated presynaptic inhibition at cerebellar GABAergic synapses: a characterization of molecular mechanisms

Satake, Shin’Ichiro; Saitow, Fumihito; Rusakov, Dmitri; Konishi, Shiro
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/2004 EN
Relevância na Pesquisa
46.52%
A major subtype of glutamate receptors, AMPA receptors (AMPARs), are generally thought to mediate excitation at mammalian central synapses via the ionotropic action of ligand-gated channel opening. It has recently emerged, however, that synaptic activation of AMPARs by glutamate released from the climbing fibre input elicits not only postsynaptic excitation but also presynaptic inhibition of GABAergic transmission onto Purkinje cells in the cerebellar cortex. Although presynaptic inhibition is critical for information processing at central synapses, the molecular mechanisms by which AMPARs take part in such actions are not known. This study therefore aimed at further examining the properties of AMPAR-mediated presynaptic inhibition at GABAergic synapses in the rat cerebellum. Our data provide evidence that the climbing fibre-induced inhibition of GABA release from interneurons depends on AMPAR-mediated activation of GTP-binding proteins coupled with down-regulation of presynaptic voltage-dependent Ca2+ channels. A Gi/o-protein inhibitor, N-ethylmaleimide, selectively abolished the AMPAR-mediated presynaptic inhibition at cerebellar GABAergic synapses but did not affect AMPAR-mediated excitatory actions on Purkinje cells. Furthermore...

Requirement of neuronal connexin36 in pathways mediating presynaptic inhibition of primary afferents in functionally mature mouse spinal cord

Bautista, Wendy; Nagy, James I; Dai, Yue; McCrea, David A
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
46.53%
Electrical synapses formed by gap junctions containing connexin36 (Cx36) promote synchronous activity of interneurones in many regions of mammalian brain; however, there is limited information on the role of electrical synapses in spinal neuronal networks. Here we show that Cx36 is widely distributed in the spinal cord and is involved in mechanisms that govern presynaptic inhibition of primary afferent terminals. Electrophysiological recordings were made in spinal cord preparations from 8- to 11-day-old wild-type and Cx36 knockout mice. Several features associated with presynaptic inhibition evoked by conditioning stimulation of low threshold hindlimb afferents were substantially compromised in Cx36 knockout mice. Dorsal root potentials (DRPs) evoked by low intensity stimulation of sensory afferents were reduced in amplitude by 79% and in duration by 67% in Cx36 knockouts. DRPs were similarly affected in wild-types by bath application of gap junction blockers. Consistent with presynaptic inhibition of group Ia muscle spindle afferent terminals on motoneurones described in adult cats, conditioning stimulation of an adjacent dorsal root evoked a long duration inhibition of monosynaptic reflexes recorded from the ventral root in wild-type mice...

Presynaptic Inhibition of Olfactory Sensory Neurons: New Mechanisms and Potential Functions

McGann, John P.
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
46.52%
Presynaptic inhibition is the suppression of neurotransmitter release from a neuron by inhibitory input onto its presynaptic terminal. In the olfactory system, the primary sensory afferents from the olfactory neuroepithelium to the brain’s olfactory bulb are strongly modulated by a presynaptic inhibition that has been studied extensively in brain slices and in vivo. In rodents, this inhibition is mediated by γ-amino butyric acid (GABA) and dopamine released from bulbar interneurons. The specialized GABAergic circuit is now well understood to include a specific subset of GAD65-expressing periglomerular interneurons that stimulate presynaptic GABAB receptors to reduce presynaptic calcium conductance. This inhibition is organized to permit the selective modulation of neurotransmitter release from specific populations of olfactory sensory neurons based on their odorant receptor expression, includes specialized microcircuits to create a tonically active inhibition and a separate feedback inhibition evoked by sensory input, and can be modulated by centrifugal projections from other brain regions. Olfactory nerve output can also be modulated by dopaminergic circuitry, but this literature is more difficult to interpret. Presynaptic inhibition of olfactory afferents may extend their dynamic range but could also create state-dependent or odorant-specific sensory filters on primary sensory representations. New directions exploring this circuit’s role in olfactory processing are discussed.

Changes in binomial parameters of quantal release at crustacean motor axon terminals during presynaptic inhibition.

Atwood, H L; Tse, F W
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1988 EN
Relevância na Pesquisa
46.5%
1. The effects of presynaptic inhibition on quantal release of transmitter were investigated at neuromuscular junctions of the motor axon supplying one of the limb muscles of a crab (Pachygrapsus crassipes). 2. Binomial analysis of transmitter release recorded at selected neuromuscular junctions with an extracellular 'macro-patch' electrode indicated high probability of release (p) from a limited number of available sites (n). During presynaptic inhibition, both n and p were reduced. 3. The binomial model provided a good description of results from non-inhibited junctions. During presynaptic inhibition, results from some junctions could be described by the binomial model, while those from other junctions could not. An interpretation of this finding is that presynaptic inhibition differentially affects the probability of release at various release sites of the neuromuscular junctional complex. 4. A morphological study of the region of transmitter release under the macropatch electrode was made. Release-dependent uptake of horseradish peroxidase (HRP) into presynaptic terminals was restricted to the region under the recording electrode, by perfusing the preparation with calcium-free solution containing HRP. Transmitter release, and HRP uptake...

Relationships between presynaptic inhibition and static postural sway in subjects with and without diabetic neuropathy

Chun, Jihyun; Hong, Junggi;
Fonte: The Society of Physical Therapy Science Publicador: The Society of Physical Therapy Science
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
46.58%
[Purpose] Diabetic peripheral neuropathy can often lead to balance impairment. The spinal reflex is a mechanism that is reportedly important for balance, but it has not been investigated in diabetic peripheral neuropathy patients. Moreover, inhibitory or facilitatory behavior of the spinal reflex—known as presynaptic inhibition—is essential for controlling postural sway. The purpose of this study was to compare the differences in as presynaptic inhibition and balance in subjects with and without diabetic peripheral neuropathy to determine the influence of presynaptic inhibition on balance in diabetic peripheral neuropathy patients. [Subjects and Methods] Presynaptic inhibition and postural sway were tested in eight patients (mean age, 58±6 years) and eight normal subjects (mean age, 59±7 years). The mean percent difference in conditioned reflex amplitude relative to the unconditioned reflex amplitude was assessed to calculate as presynaptic inhibition. The single-leg balance index was measured using a computerized balance-measuring device. [Results] The diabetic peripheral neuropathy group showed lower presynaptic inhibition (47±30% vs. 75±22%) and decreased balance (0.65±0.24 vs. 0.38±0.06) as compared with the normal group. No significant correlation was found between as presynaptic inhibition and balance score (R=0.37). [Conclusion] Although the decreased as presynaptic inhibition observed in diabetic peripheral neuropathy patients may suggest central nervous system involvement...