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Excitatory Postsynaptic Potentials (excitatory + postsynaptic_potential)
Kinds of Excitatory Postsynaptic Potentials Selected AbstractsDevelopmental alterations in the functional properties of excitatory neocortical synapsesTHE JOURNAL OF PHYSIOLOGY, Issue 9 2009Dirk Feldmeyer In the neocortex, most excitatory, glutamatergic synapses are established during the first 4,5 weeks after birth. During this period profound changes in the properties of synaptic transmission occur. Excitatory postsynaptic potentials (EPSPs) at immature synaptic connections are profoundly and progressively reduced in response to moderate to high frequency (5,100 Hz) stimulation. With maturation, this frequency-dependent depression becomes progressively weaker and may eventually transform into a weak to moderate EPSP facilitation. In parallel to changes in the short-term plasticity, a reduction in the synaptic reliability occurs at most glutamatergic neocortical synapses: immature synapses show a high probability of neurotransmitter release as indicated by their low failure rate and small EPSP amplitude variation. This high reliability is reduced in mature synapses, which show considerably higher failure rates and more variable EPSP amplitudes. During early neocortical development synaptic vesicle pools are not yet fully differentiated and their replenishment may be slow, thus resulting in EPSP amplitude depression. The decrease in the probability of neurotransmitter release may be the result of an altered Ca2+ control in the presynaptic terminal with a reduced Ca2+ influx and/or a higher Ca2+ buffering capacity. This may lead to a lower synaptic reliability and a weaker short-term synaptic depression with maturation. [source] Impaired M-Current and Neuronal ExcitabilityEPILEPSIA, Issue 2002Motohiro Okada Summary: ,Purpose: Benign familial neonatal convulsions (BFNC), a hereditary epilepsy, occurs specifically in newborns and remits spontaneously after this period. Several mutations of either KCNQ2 or KCNQ3, members of the KCNQ-related K+ -channel (KCNQ-channel) family, were identified as a cause of BFNC. Such mutations impair KCNQ-related M- current, an element of the inhibitory system in the central nervous system (CNS), and therefore are thought to result in neuronal hyperexcitability. Methods: To clarify the pathogenesis of BFNC, this study investigated the effects of the KCNQ channel on propagation of neuronal excitability using a 64-channel multielectrode dish (MED64) system for novel two-dimensional monitoring of evoked field potentials including fiber volley (FV) and field excitatory postsynaptic potential (fEPSP). Results: Dup996, a selective KCNQ-channel inhibitor, did not affect the amplitude of FV or fEPSP, but enhanced the FV and fEPSP propagation. The ,-aminobutyric acid (GABA)A -receptor antagonist, bicuculline, enhanced their propagation, whereas ,-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/glutamate-receptor antagonist, DNQX, reduced both amplitude and propagation of fEPSP without affecting those of FV. Under the condition of GABAA -receptor blockade by bicuculline, Dup996 enhanced the amplitude of fEPSP and propagation of FV and fEPSP without affecting the amplitude of FV. Dup996 enhanced the stimulating effects of bicuculline on the propagation and amplitude of FV and fEPSP, but it did not affect the inhibiting effects of DNQX. Conclusions: These results suggest that the occurrence of BFNC cannot be produced by KCNQ-channel dysfunction alone but by reciprocal action between impaired KCNQ channel and the other unknown. [source] Intramuscular AAV delivery of NT-3 alters synaptic transmission to motoneurons in adult ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2010Jeffrey C. Petruska Abstract We examined whether elevating levels of neurotrophin-3 (NT-3) in the spinal cord and dorsal root ganglion (DRG) would alter connections made by muscle spindle afferent fibers on motoneurons. Adeno-associated virus (AAV) serotypes AAV1, AAV2 and AAV5, selected for their tropism profile, were engineered with the NT-3 gene and administered to the medial gastrocnemius muscle in adult rats. ELISA studies in muscle, DRG and spinal cord revealed that NT-3 concentration in all tissues peaked about 3 months after a single viral injection; after 6 months NT-3 concentration returned to normal values. Intracellular recording in triceps surae motoneurons revealed complex electrophysiological changes. Moderate elevation in cord NT-3 resulted in diminished segmental excitatory postsynaptic potential (EPSP) amplitude, perhaps as a result of the observed decrease in motoneuron input resistance. With further elevation in NT-3 expression, the decline in EPSP amplitude was reversed, indicating that NT-3 at higher concentration could increase EPSP amplitude. No correlation was observed between EPSP amplitude and NT-3 concentration in the DRG. Treatment with control viruses could elevate NT-3 levels minimally resulting in measurable electrophysiological effects, perhaps as a result of inflammation associated with injection. EPSPs elicited by stimulation of the ventrolateral funiculus underwent a consistent decline in amplitude independent of NT-3 level. These novel correlations between modified NT-3 expression and single-cell electrophysiological parameters indicate that intramuscular administration of AAV(NT-3) can exert long-lasting effects on synaptic transmission to motoneurons. This approach to neurotrophin delivery could be useful in modifying spinal function after injury. [source] Prokineticin 2 depolarizes paraventricular nucleus magnocellular and parvocellular neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2007Erik A. Yuill Abstract Blind whole-cell patch-clamp techniques were used to examine the effects of prokineticin 2 (PK2) on the excitability of magnocellular (MNC), parvocellular preautonomic (PA), and parvocellular neuroendocrine (NE) neurons within the hypothalamic paraventricular nucleus (PVN) of the rat. The majority of MNC neurons (76%) depolarized in response to 10 nm PK2, effects that were eliminated in the presence of tetrodotoxin (TTX). PK2 also caused an increase in excitatory postsynaptic potential (EPSP) frequency, a finding that was confirmed by voltage clamp recordings demonstrating increases in excitatory postsynaptic current (EPSC) frequency. The depolarizing effects of PK2 on MNC neurons were also abolished by kynurenic acid (KA), supporting the conclusion that the effects of PK2 are mediated by the activation of glutamate interneurons within the hypothalamic slice. PA (68%) and NE (67%) parvocellular neurons also depolarized in response to 10 nm PK2. However, in contrast to MNC neurons, these effects were maintained in TTX, indicating that PK2 directly affects PA and NE neurons. PK2-induced depolarizations observed in PA and NE neurons were found to be concentration-related and receptor mediated, as experiments performed in the presence of A1MPK1 (a PK2 receptor antagonist) abolished the effects of PK2 on these subpopulations of neurons. The depolarizing effects of PK2 on PA and NE neurons were also shown to be abolished by PD 98059 (a mitogen activated protein kinase (MAPK) inhibitor) suggesting that PK2 depolarizes PVN parvocellular neurons through a MAPK signalling mechanism. In combination, these studies have identified separate cellular mechanisms through which PK2 influences the excitability of different subpopulations of PVN neurons. [source] Melatonin inhibits hippocampal long-term potentiationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2005Louisa M. Wang Abstract The goal of this study is to investigate the effect of the hormone melatonin on long-term potentiation and excitability measured by stimulating the Schaffer collaterals and recording the field excitatory postsynaptic potential from the CA1 dendritic layer in hippocampal brain slices from mice. Application of melatonin produced a concentration-dependent inhibition of the induction of long-term potentiation, with a concentration of 100 nm producing an ,,50% inhibition of long-term potentiation magnitude. Long-duration melatonin treatments of 6 h were also effective at reducing the magnitude of long-term potentiation. Melatonin (100 nm) did not alter baseline evoked responses or paired-pulse facilitation recorded at this synapse. The inhibitory actions of melatonin were prevented by application of the melatonin (MT) receptor antagonist luzindole as well as the MT2 receptor subtype antagonist 4-phenyl-2-propionamidotetraline. These inhibitory actions of melatonin were lost in mice deficient in MT2 receptors but not those deficient in MT1 receptors. In addition, application of the protein kinase A inhibitor H-89 both mimicked the effects of melatonin and precluded further inhibition by melatonin. Finally, the application an activator of adenylyl cyclase, forskolin, overcame the inhibitory effects of melatonin on LTP without affecting the induction of long-term potentiation on its own. These results suggest that hippocampal synaptic plasticity may be constrained by melatonin through a mechanism involving MT2-receptor-mediated regulation of the adenylyl cyclase,protein kinase A pathway. [source] Ionic currents underlying rhythmic bursting of ventral mossy cells in the developing mouse dentate gyrusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2003Shozo Jinno Abstract The electrophysiological properties of mossy cells were examined in developing mouse hippocampal slices using whole-cell patch-clamp techniques, with particular reference to the dorsoventral difference. Dorsal mossy cells exhibited a higher spontaneous excitatory postsynaptic potential (EPSP) frequency and larger maximal EPSP amplitude than ventral mossy cells. On the other hand, the blockade of synaptic inputs with glutamatergic and GABAergic antagonists disclosed a remarkable dorsoventral difference in the intrinsic activity: none (0/27) of the dorsal mossy cells showed intrinsic bursting, whereas the majority (35/47) of the ventral mossy cells exhibited intrinsic rhythmic bursting. To characterize the ionic currents underlying the rhythmic bursting of mossy cells, we used somatic voltage-clamp recordings in the subthreshold voltage range. Ventral bursting cells possessed both hyperpolarization-activated current (Ih) and persistent sodium current (INaP), whereas dorsal and ventral nonbursting cells possessed Ih but no INaP. Blockade of Ih with cesium did not affect the intrinsic bursting of ventral mossy cells. In contrast, the blockade of INaP with tetrodotoxin or phenytoin established a stable subthreshold membrane potential in ventral bursting cells. The current,voltage curve of ventral bursting cells showed a region of tetrodotoxin-sensitive negative slope conductance between ,55 mV and a spike threshold (, ,45 mV). On the other hand, no subthreshold calcium conductances played a significant role in the intrinsic bursting of ventral mossy cells. These observations demonstrate the heterogeneous electrophysiological properties of hilar mossy cells, and suggest that the subthreshold INaP plays a major role in the intrinsic rhythmic bursting of ventral mossy cells. [source] Contribution of T-type VDCC to TEA-induced long-term synaptic modification in hippocampal CA1 and dentate gyrusHIPPOCAMPUS, Issue 5 2002Dong Song Abstract We have previously reported that exposure to the K+ channel blocker tetraethylammonium (TEA), 25 mM, induces long-term potentiation (LTP) in CA1, but not in the dentate gyrus (DG), of the rat hippocampal slice. During TEA application, stimulation of excitatory afferents results in a strong depolarizing potential after the fast excitatory postsynaptic potential (EPSP) in CA1, but not in DG. We hypothesized that the differential effect of TEA on long-term synaptic modification in CA1 and DG results from different levels of TEA-elicited depolarization in the two cell types. Additional pharmacological studies showed that blockade of T-type voltage-dependent calcium channels (VDCCs) decreased both the magnitude of LTP and the late, depolarizing potential in CA1. Blockade of L-type VDCCs had no such effect. Using computer models of morphologically reconstructed CA1 pyramidal cells and DG granule cells, we tested our hypothesis by simulating the relative intracellular Ca2+ accumulation and membrane potential changes mediated by T-type and L-type VDCCs. Simulation results using pyramidal cell models showed that, with decreased maximum conductance of TEA-sensitive potassium channels, synaptic inputs elicited strong depolarizing potentials similar to those observed with intracellular recording. During this depolarization, VDCCs were opened and resulted in a large intracellular Ca2+ accumulation that presumably caused LTP. When T-type VDCCs were blocked, the magnitudes of both the Ca2+ accumulation and the late depolarizing potential were decreased substantially. Simulated blockade of L-type VDCCs had only a minor effect. Together, our modeling and experimental studies indicate that T-type VDCCs, rather than L-type VDCCs, are primarily responsible for facilitating the depolarizing potential caused by TEA and for the consequent Ca2+ influx. Thus, our findings strongly suggest that the induction of TEA-LTP in CA1 depends primarily on T-type, rather than L-type, VDCCs. Simulation results using modeled granule cells suggests that the failure of TEA to induce LTP in DG is partly due to a low density of T-type VDCCs in granule cell membranes. Hippocampus 2002;12:689,697. © 2002 Wiley-Liss, Inc. [source] A new role for P2 receptors: talking with calcium-activated potassium channelsNEUROGASTROENTEROLOGY & MOTILITY, Issue 11 2007P. P. Bertrand Abstract Purinergic fast synaptic transmission may play a very subtle role in regulating the excitability of enteric circuits. That is one of the important findings in a new paper by Ren and Galligan in the current issue of this Journal. They first provide compelling evidence that P2X3 receptors (ionotropic purine receptors) are expressed by guinea-pig motor and interneurons and that these subtypes mediate the purinergic fast excitatory postsynaptic potential (EPSP). They also found that the P2X3 -mediated depolarization was often followed by a hyperpolarization. This is an intriguing finding because if the purinergic fast EPSPs are also followed by a hyperpolarization, then it could play a role in truncating bursts of synaptic potentials or in shaping periodic synaptic input. The hyperpolarization is caused by calcium entry through the P2X3 receptor which then activates a calcium-activated potassium (KCa) channel. Surprisingly, the hyperpolarization was not affected by any of the standard blockers of calcium- or voltage-activated K+ channels suggesting that a novel KCa channel is present in the enteric neurons. Such a wide-spread channel could well have an important physiological role and could be an important new drug target for regulating reflex activity in the enteric nervous system. [source] Electrical behaviour of interleukin-1 beta (IL-1,) and prostaglandin-E2 (PGE2) on colonic myenteric neuronesNEUROGASTROENTEROLOGY & MOTILITY, Issue 4 2002A. Kelles Abstract,Intracellular recordings were used to examine the effects on electrical and synaptic behaviour of interleukin (IL)-1, and prostaglandin E2(PGE2) on myenteric neurones of the guinea-pig colon. Application of IL-1, and PGE2resulted in a concentration-dependent slow depolarization with enhanced spike discharge in, respectively, 45% (21/47) and 83% (33/41) of the impaled colonic neurones. Administration of IL-1, in three neurones (6%) elicited a hyperpolarization. Responses remained during tetrodotoxin application, indicative of a direct effect of both substances on the impaled neurones. The effects of IL-1, remained in the presence of indomethacine, a prostaglandin synthase inhibitor. Responses were seen in both nitric oxide synthase- and choline acetyl transferase-immunoreactive neurones. IL-1, evoked a 26% reduction of the fast excitatory postsynaptic potential. These results indicate that the application of IL-1, and PGE2evoke direct excitatory actions on a subset of myenteric neurones. For IL-1,, direct inhibition and presynaptic inhibition of the fast excitatory postsynaptic potential has also been found. In the distal colon, responses to IL-1, are not mediated through PGE2pathways. [source] The pharmacological and physiological profile of glutamate receptors at the Drosophila larval neuromuscular junctionPHYSIOLOGICAL ENTOMOLOGY, Issue 2 2005Deval Bhatt Abstract.,Drosophila larval muscles are commonly used for developmental assessment in regard to various mutations of synaptically relevant molecules. In addition, the molecular sequence of the glutamate receptors on the muscle fibre have been described; however, the pharmacological profiles to known agonists and antagonists have yet to be reported. Here, the responses of N -methyl- d -aspartic acid, ,-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA), l -glutamate, kainate, quisqualic acid, NBQX, AP5 and DNQX are characterized with regard to synaptic transmission and direct effects on the muscle fibres. The muscle fibres depolarize to application of glutamate or quisqualate and the excitatory postsynaptic potential (EPSP) amplitudes are diminished. Kainate does not alter the muscle membrane potential but does reduce the EPSP amplitude. The known antagonists NBQX, AP5 and DNQX have no substantial effect on synaptic transmission at 1 mm, nor do they block the response of quisqualate. Kainate may be acting as a postsynaptic antagonist or via autoreceptors presynaptically to reduce evoked transmission. [source] Visualization of transmitter release with zinc fluorescence detection at the mouse hippocampal mossy fibre synapseTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Jing Qian Exocytosis of synaptic vesicle contents defines the quantal nature of neurotransmitter release. Here we developed a technique to directly assess exocytosis by measuring vesicular zinc release with the zinc-sensitive dye FluoZin-3 at the hippocampal mossy fibre (MF) synapse. Using a photodiode, we were able to clearly resolve the zinc fluorescence transient ([Zn2+]t) with a train of five action potentials in mouse hippocampal brain slices. The vesicular origin of [Zn2+]t was verified by the lack of zinc signal in vesicular zinc transporter Znt3-deficient mice. Manipulating release probability with the application of neuromodulators such as DCG IV, 4-aminopyridine and forskolin as well as a paired train stimulation protocol altered both the [Zn2+]t and the field excitatory postsynaptic potential (fEPSP) coordinately, strongly indicating that zinc is co-released with glutamate during exocytosis. Since zinc ions colocalize with glutamate in small clear vesicles and modulate postsynaptic excitability at NMDA and GABA receptors, the findings establish zinc as a cotransmitter during physiological signalling at the mossy fibre synapse. The ability to directly visualize release dynamics with zinc imaging will facilitate the exploration of the molecular pharmacology and plasticity of exocytosis at MF synapses. [source] A novel role for MNTB neuron dendrites in regulating action potential amplitude and cell excitability during repetitive firingEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2008Richardson N. Leão Abstract Principal cells of the medial nucleus of the trapezoid body (MNTB) are simple round neurons that receive a large excitatory synapse (the calyx of Held) and many small inhibitory synapses on the soma. Strangely, these neurons also possess one or two short tufted dendrites, whose function is unknown. Here we assess the role of these MNTB cell dendrites using patch-clamp recordings, imaging and immunohistochemistry techniques. Using outside-out patches and immunohistochemistry, we demonstrate the presence of dendritic Na+ channels. Current-clamp recordings show that tetrodotoxin applied onto dendrites impairs action potential (AP) firing. Using Na+ imaging, we show that the dendrite may serve to maintain AP amplitudes during high-frequency firing, as Na+ clearance in dendritic compartments is faster than axonal compartments. Prolonged high-frequency firing can diminish Na+ gradients in the axon while the dendritic gradient remains closer to resting conditions; therefore, the dendrite can provide additional inward current during prolonged firing. Using electron microscopy, we demonstrate that there are small excitatory synaptic boutons on dendrites. Multi-compartment MNTB cell simulations show that, with an active dendrite, dendritic excitatory postsynaptic currents (EPSCs) elicit delayed APs compared with calyceal EPSCs. Together with high- and low-threshold voltage-gated K+ currents, we suggest that the function of the MNTB dendrite is to improve high-fidelity firing, and our modelling results indicate that an active dendrite could contribute to a ,dual' firing mode for MNTB cells (an instantaneous response to calyceal inputs and a delayed response to non-calyceal dendritic excitatory postsynaptic potentials). [source] Contribution of NMDA receptor NR2B subunit to synaptic plasticity during associative learning in behaving ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2007Mauricio Valenzuela-Harrington Abstract The difference in the amounts of NR2 subunits contained in NMDA receptors of the hippocampus has been related to their different involvement in activity-dependent synaptic plasticity. Here, we show that Ro 25-6981, a high-affinity and selective blocker of NMDA receptors containing NR2B subunits, is able to block the acquisition of a trace conditioning paradigm in adult rats, a task that requires the active participation of hippocampal circuits. Reconditioning with the same trace paradigm was also prevented by Ro 25-6981. In addition, we show that the slope of monosynaptic field excitatory postsynaptic potentials evoked at the dentate gyrus by single pulses presented to the medial perforant pathway increases significantly across conditioning sessions and during reconditioning, in a linear relationship with the increase in the number of classically conditioned eyelid responses. Administration of Ro 25-6981 prevented these learning-related changes in synaptic strength at the perforant pathway,dentate granule cell synapse. The present results suggest the involvement of NR2B-containing NMDA receptors in hippocampal functions related to both associative learning and activity-dependent synaptic plasticity. [source] Effect of cortical spreading depression on synaptic transmission of rat hippocampal tissuesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2006Brigitta Wernsmann Abstract Cortical spreading depression (CSD) is believed to be a putative neuronal mechanism underlying migraine aura and subsequent pain. In vitro and ex vivo/in vitro brain slice techniques were used to investigate CSD effects on the field excitatory postsynaptic potentials (fEPSP) and tetanus-induced long-term potentiation (LTP) in combined rat hippocampus,cortex slices. Induction of CSD in combined hippocampus,cortex slices in which DC negative deflections did not propagate from neocortex to hippocampus significantly augmented fEPSP amplitude and LTP in the hippocampus. Propagation of CSD to the hippocampus resulted in a transient suppression followed by reinstatement of fEPSP with amplitude of pre-CSD levels. LTP was inhibited when DC potential shifts were recorded in the hippocampus. Furthermore, CSD was induced in anaesthetized rats and, thereafter, hippocampal tissues were examined in vitro. LTP was significantly enhanced in hippocampal slices obtained from ipsilateral site to the hemisphere in which CSD was evoked. The results indicate the disturbances of hippocampal synaptic transmission triggered by propagation of CSD. This perturbation of hippocampal synaptic transmission induced by CSD may relate to some symptoms occurring during migraine attacks, such as amnesia and hyperactivity. [source] Glutamatergic input governs periodicity and synchronization of bursting activity in oxytocin neurons in hypothalamic organotypic culturesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2003Jean-Marc Israel Abstract During suckling, oxytocin (OT) neurons display a bursting electrical activity, consisting of a brief burst of action potentials which is synchronized throughout the OT neuron population and which periodically occurs just before each milk ejection in the lactating rat. To investigate the basis of such synchronization, we performed simultaneous intracellular recordings from pairs of OT neurons identified retrospectively by intracellular fluorescent labelling and immunocytochemistry in organotypic slice cultures derived from postnatal rat hypothalamus. A spontaneous bursting activity was recorded in 65% of OT neurons; the remaining showed only a slow, irregular activity. Application of OT triggered bursts in nonbursting neurons and accelerated bursting activity in spontaneously bursting cells. These cultures included rare vasopressinergic neurons showing no bursting activity and no reaction to OT. Bursts occurred simultaneously in all pairs of bursting OT neurons but, as in vivo, there were differences in burst onset, amplitude and duration. Coordination of firing was not due to electrotonic coupling because depolarizing one neuron in a pair had no effect on the membrane potential of its partner and halothane and proprionate did not desynchronize activity. On the other hand, bursting activity was superimposed on volleys of excitatory postsynaptic potentials (EPSPs) which occurred simultaneously in pairs of neurons. EPSPs, and consequently action potentials, were reversibly blocked by the non-NMDA glutamatergic receptor antagonist CNQX. Taken together, these data, obtained from organotypic cultures, strongly suggest that a local hypothalamic network governs synchronization of bursting firing in OT neurons through synchronous afferent volleys of EPSPs originating from intrahypothalamic glutamatergic inputs. [source] Endogenous and exogenous dopamine presynaptically inhibits glutamatergic reticulospinal transmission via an action of D2 -receptors on N-type Ca2+ channelsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003Erik Svensson Abstract In this study, the effects of exogenously applied and endogenously released dopamine (DA), a powerful modulator of the lamprey locomotor network, are examined on excitatory glutamatergic synaptic transmission between reticulospinal axons and spinal neurons. Bath application of DA (1,50 µm) reduced the amplitude of monosynaptic reticulospinal-evoked glutamatergic excitatory postsynaptic potentials (EPSPs). The effect of DA was blocked by the D2 -receptor antagonist eticlopride, and mimicked by the selective D2 -receptor agonist 2,10,11 trihydroxy- N -propyl-noraporphine hydrobromide (TNPA). Bath application of the DA reuptake blocker bupropion, which increases the extracellular level of dopamine, also reduced the monosynaptic EPSP amplitude. This effect was also blocked by the D2 -receptor antagonist eticlopride. To investigate if the action of DA was exerted at the presynaptic level, the reticulospinal axon action potentials were prolonged by administering K+ channel antagonists while blocking l -type Ca2+ channels. A remaining Ca2+ component, mainly dependent on N and P/Q channels, was depressed by DA. When DA (25,50 µm) was applied in the presence of ,-conotoxin GVIA, a toxin specific for N-type Ca2+ channels, it failed to affect the monosynaptic EPSP amplitude. DA did not affect the response to extracellularly ejected d -glutamate, the postsynaptic membrane potential, or the electrical component of the EPSPs. DA thus acts at the presynaptic level to modulate reticulospinal transmission. [source] Synaptic stimulation of nicotinic receptors in rat sympathetic ganglia is followed by slow activation of postsynaptic potassium or chloride conductancesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2000Oscar Sacchi Abstract Two slow currents have been described in rat sympathetic neurons during and after tetanization of the whole preganglionic input. Both effects are mediated by nicotinic receptors activated by native acetylcholine (ACh). A first current, indicated as IAHPsyn, is calcium dependent and voltage independent, and is consistent with an IAHP -type potassium current sustained by calcium ions accompanying the nicotinic synaptic current. The conductance activated by a standard synaptic train was ,,3.6 nS per neuron; it was detected in isolation in 14 out of a 52-neuron sample. A novel current, IADPsyn, was described in 42/52 of the sample as a post-tetanic inward current, which increased in amplitude with increasing membrane potential negativity and exhibited a null-point close to the holding potential and the cell momentary chloride equilibrium potential. IADPsyn developed during synaptic stimulation and decayed thereafter according to a single exponential (mean ,,= 148.5 ms) in 18 neurons or according to a two-exponential time course (, = 51.8 and 364.9 ms, respectively) in 19 different neurons. The mean peak conductance activated was ,,20 nS per neuron. IADPsyn was calcium independent, it was affected by internal and external chloride concentration, but was insensitive to specific blockers (anthracene-9-carboxylic acid, 9AC) of the chloride channels open in the resting neuron. It is suggested that gADPsyn represents a specific chloride conductance activatable by intense nicotinic stimulation; in some neurons it is even associated with single excitatory postsynaptic potentials (EPSCs). Both IAHP and IADPsyn are apparently devoted to reduce neuronal excitability during and after intense synaptic stimulation. [source] Hippocampal synaptic transmission and LTP in vivo are intact following bilateral vestibular deafferentation in the ratHIPPOCAMPUS, Issue 4 2010Yiwen Zheng Abstract Numerous studies in animals and humans have shown that damage to the vestibular system in the inner ear results in spatial memory deficits, presumably because areas of the brain such as the hippocampus require vestibular input to accurately represent the spatial environment. Consistent with this hypothesis, studies in animals have demonstrated that complete bilateral vestibular deafferentation (BVD) causes a disruption of place cell firing as well as theta activity. The aim of this study was to investigate whether BVD in rats affects baseline field potentials (field excitatory postsynaptic potentials and population spikes) and long-term potentiation (LTP) in CA1 and the dentate gyrus (DG) of awake freely moving rats up to 43 days post-BVD and of anesthetized rats at 7 months post-BVD. Compared to sham controls, BVD had no significant effect on either baseline field potentials or LTP in either condition. These results suggest that although BVD interferes with the encoding, consolidation, and/or retrieval of spatial memories and the function of place cells, these changes are not related to detectable in vivo decrements in basal synaptic transmission or LTP, at least in the investigated pathways. © 2009 Wiley-Liss, Inc. [source] Cholinergic suppression of excitatory synaptic responses in layer II of the medial entorhinal cortexHIPPOCAMPUS, Issue 2 2007Bassam N. Hamam Abstract Theta-frequency (4,12 Hz) electroencephalographic activity is thought to play a role in mechanisms mediating sensory and mnemonic processing in the entorhinal cortex and hippocampus, but the effects of acetylcholine on excitatory synaptic inputs to the entorhinal cortex are not well understood. Field excitatory postsynaptic potentials (fEPSPs) evoked by stimulation of the piriform (olfactory) cortex were recorded in the medial entorhinal cortex during behaviors associated with theta activity (active mobility) and were compared with those recorded during nontheta behaviors (awake immobility and slow wave sleep). Synaptic responses were smaller during behavioral activity than during awake immobility and sleep, and responses recorded during movement were largest during the negative phase of the theta rhythm. Systemic administration of cholinergic agonists reduced the amplitude of fEPSPs, and the muscarinic receptor blocker scopolamine strongly enhanced fEPSPs, suggesting that the theta-related suppression of fEPSPs is mediated in part by cholinergic inputs. The reduction in fEPSPs was investigated using in vitro intracellular recordings of EPSPs in Layer II neurons evoked by stimulation of Layer I afferents. Constant bath application of the muscarinic agonist carbachol depolarized membrane potential and suppressed EPSP amplitude in Layer II neurons. The suppression of EPSPs was not associated with a substantial change in input resistance, and could not be accounted for by a depolarization-induced reduction in driving force on the EPSP. The GABAA receptor-blocker bicuculline (50 ,M) did not prevent the cholinergic suppression of EPSPs, suggesting that the suppression is not dependent on inhibitory mechanisms. Paired-pulse facilitation of field and intracellular EPSPs were enhanced by carbachol, indicating that the suppression is likely due to inhibition of presynaptic glutamate release. These results indicate that, in addition to well known effects on postsynaptic conductances that increase cellular excitability, cholinergic activation in the entorhinal cortex results in a strong reduction in strength of excitatory synaptic inputs from the piriform cortex. © 2006 Wiley-Liss, Inc. [source] Analysis and comparison of morphological reconstructions of hippocampal field CA1 pyramidal cellsHIPPOCAMPUS, Issue 3 2005José Ambros-Ingerson Abstract Morphological reconstructions have become a routine and valuable tool for neuroscientists. The accuracy of reconstructions is a matter of considerable interest given that they are widely used in computational studies of neural function. Despite their wide usage, comparisons of reconstructions obtained using various methodologies are lacking. We reviewed reconstructions of hippocampal CA1 pyramidal cells from five published studies and found marked differences in some of the most basic measurements. For four of the five studies means of total cell length clustered in the 11,479,13,417-,m range. The remaining study had a significantly larger value for this index at 16,992 ± 5,788 ,m. Surface area means varied more than 4-fold from 16,074 to 67,102 ,m2. Volume means varied more than 8-fold from 3,828 to 30,384 ,m3. Simulated passive input resistance means varied from 38.0 to 172.1 M,, reflecting the variability in cell dimensions. Estimates of the electrotonic length varied from 1.26 to 1.56. In two reconstructions used in previously published studies, simulated somatic excitatory postsynaptic potentials (EPSPs) varied 2,4-fold in amplitude, time to peak and half-width, for synaptic inputs at similar locations. Substantial jitter on the z -axis was identified as one likely source of the discrepancy in total cell length, while substantial differences in diameter measurements across studies, and sometimes within the same study, accounted for the variability in surface area and volume. While some part of the observed variability is surely due to the diversity of CA1 pyramidal cells, our analysis suggests that a substantial portion stemmed from methodological inconsistencies and from technological limitations. Suggestions are made for improving the quality and usefulness of morphological reconstructions. We conclude that reconstructions across studies have substantial variability in measures that are very relevant to neuronal function. Consequently, modelers are advised to use more than just one reconstructed cell in their simulations of neural function. © 2004 Wiley-Liss, Inc. [source] Reduction in glutamate uptake is associated with extrasynaptic NMDA and metabotropic glutamate receptor activation at the hippocampal CA1 synapse of aged ratsAGING CELL, Issue 5 2010Brigitte Potier Summary This study aims to determine whether the regulation of extracellular glutamate is altered during aging and its possible consequences on synaptic transmission and plasticity. A decrease in the expression of the glial glutamate transporters GLAST and GLT-1 and reduced glutamate uptake occur in the aged (24,27 months) Sprague,Dawley rat hippocampus. Glutamatergic excitatory postsynaptic potentials recorded extracellularly in ex vivo hippocampal slices from adult (3,5 months) and aged rats are depressed by DL-TBOA, an inhibitor of glutamate transporter activity, in an N -Methyl- d- Aspartate (NMDA)-receptor-dependent manner. In aged but not in young rats, part of the depressing effect of DL-TBOA also involves metabotropic glutamate receptor (mGluRs) activation as it is significantly reduced by the specific mGluR antagonist d-methyl-4-carboxy-phenylglycine (MCPG). The paired-pulse facilitation ratio, a functional index of glutamate release, is reduced by MCPG in aged slices to a level comparable to that in young rats both under control conditions and after being enhanced by DL-TBOA. These results suggest that the age-associated glutamate uptake deficiency favors presynaptic mGluR activation that lowers glutamate release. In parallel, 2 Hz-induced long-term depression is significantly decreased in aged animals and is fully restored by MCPG. All these data indicate a facilitated activation of extrasynaptic NMDAR and mGluRs in aged rats, possibly because of an altered distribution of glutamate in the extrasynaptic space. This in turn affects synaptic transmission and plasticity within the aged hippocampal CA1 network. [source] Evidence that caspase-1 is a negative regulator of AMPA receptor-mediated long-term potentiation at hippocampal synapsesJOURNAL OF NEUROCHEMISTRY, Issue 4 2006Chengbiao Lu Abstract Best known for their pivotal role in a form of programmed cell death called apoptosis, caspases may also function in more subtle physiological processes. Caspases are present in synapses and dendrites of neurons where they can be activated in response to glutamate receptor stimulation and calcium influx. Here we tested the hypothesis that caspase-1 plays a role in modulating long-term potentiation (LTP) at hippocampal synapses. We provide evidence that caspase-1 plays a role in regulating ,-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated calcium influx and synaptic plasticity in the hippocampus. LTP of excitatory postsynaptic potentials at CA1 synapses was significantly enhanced when hippocampal slices were treated with either a pan-caspase inhibitor or a selective inhibitor of caspase-1, but not by an inhibitor of caspase-6. Inhibition of caspase-1 significantly enhanced the AMPA current-mediated component of LTP without affecting the N -methyl- d -aspartate current-mediated component. Calcium responses to AMPA were enhanced in hippocampal neurons treated with a caspase-1 inhibitor suggesting that caspase-1 normally functions to reduce AMPA receptor-mediated calcium influx. These findings suggest that, by selectively reducing AMPA currents and calcium influx, caspase-1 functions as a negative regulator of LTP at hippocampal synapses. [source] Thyroid Hormone Action: Nongenomic Modulation of Neuronal Excitability in the HippocampusJOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2009M. A. Caria Years of effort have failed to establish a generally-accepted mechanism of thyroid hormone (TH) action in the mature brain. Recently, both morphological and pharmacological evidence have supported a direct neuroactive role for the hormone and its triiodinated metabolites. However, no direct physiological validation has been available. We now describe electrophysiological studies in vivo in which we observed that local thyroxine (T4) administration promptly inhibited field excitatory postsynaptic potentials recorded in the dentate gyrus (DG) with stimulation of the medial perforant pathway, a result that was found to be especially pronounced in hypothyroid rats. In separate in vitro experiments, we observed more subtle but statistically significant responses of hippocampal slices to treatment with the hormone. The results demonstrate that baseline firing rates of CA1 pyramidal cells were modestly reduced by pulse-perfusion with T4. By contrast, administration of triiodothyronine (T3) was often noted to have modest enhancing effects on CA1 cell firing rates in hippocampal slices from euthyroid animals. Moreover, and more reliably, robust firing rate increases induced by norepinephrine were amplified when preceded by treatment with T3, whereas they were diminished by pretreatment with T4. These studies provide the first direct evidence for functional, nongenomic actions of TH leading to rapid changes in neuronal excitability in adult rat DG studied in vivo and highlight the opposing effects of T4 and T3 on norepinephrine-induced responses of CA1 cells studied in vitro. [source] Ethanol Acutely Inhibits Ionotropic Glutamate Receptor-Mediated Responses and Long-Term Potentiation in the Developing CA1 HippocampusALCOHOLISM, Issue 4 2010Michael P. Puglia Background:, Developmental ethanol (EtOH) exposure damages the hippocampus, causing long-lasting alterations in learning and memory. Alterations in glutamatergic synaptic transmission and plasticity may play a role in the mechanism of action of EtOH. This signaling is fundamental for synaptogenesis, which occurs during the third trimester of human pregnancy (first 12 days of life in rats). Methods:, Acute coronal brain slices were prepared from 7- to 9-day-old rats. Extracellular and patch-clamp electrophysiological recording techniques were used to characterize the acute effects of EtOH on ,-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR)- and N -methyl- d -aspartate receptor (NMDAR)-mediated responses and long-term potentiation (LTP) in the CA1 hippocampal region. Results:, Ethanol (40 and 80 mM) inhibited AMPAR- and NMDAR-mediated field excitatory postsynaptic potentials (fEPSPs). EtOH (80 mM) also reduced AMPAR-mediated fEPSPs in the presence of an inhibitor of Ca2+ permeable AMPARs. The effect of 80 mM EtOH on NMDAR-mediated fEPSPs was significantly greater in the presence of Mg2+. EtOH (80 mM) neither affected the paired-pulse ratio of AMPAR-mediated fEPSPs nor the presynaptic volley. The paired-pulse ratio of AMPAR-mediated excitatory postsynaptic currents was not affected either, and the amplitude of these currents was inhibited to a lesser extent than that of fEPSPs. EtOH (80 mM) inhibited LTP of AMPAR-mediated fEPSPs. Conclusions:, Acute EtOH exposure during the third-trimester equivalent of human pregnancy inhibits hippocampal glutamatergic transmission and LTP induction, which could alter synapse refinement and ultimately contribute to the pathophysiology of fetal alcohol spectrum disorder. [source] N -methyl-d-aspartate Receptor Responses Are Differentially Modulated by Noncompetitive Receptor Antagonists and Ethanol in Inbred Long-Sleep and Short-Sleep Mice: Behavior and ElectrophysiologyALCOHOLISM, Issue 12 2000Taleen Hanania Background: Short-sleep (SS) mice exhibit higher locomotor activity than do long-sleep (LS) mice when injected with low doses of ethanol or the noncompetitive N -methyl-D-aspartate receptor (NMDAR) antagonist MK-801 (dizocilpine). SS mice also have higher densities of brain NMDARs. However, two strains of LS X SS recombinant inbred (RI) mice also show differential activation to ethanol and MK-801, but have similar numbers of NMDARs. Here we used inbred LS (ILS) and SS (ISS) mice to investigate further the relationship between NMDARs and sensitivity to the stimulant effects of low doses of ethanol. Methods: Open field activity and spontaneous alternations were measured after saline or drug injection. [3H]MK-801 binding parameters were determined in hippocampus, cortex, striatum, and nucleus accumbens. Extracellular field excitatory postsynaptic potentials (fEPSPs) were recorded in the CA1 region of hippocampal slices. Results: Systemic injection of either ethanol or MK-801 increased locomotor activity to a greater extent in ISS mice than in ILS mice. The competitive NMDAR antagonist 2-carboxypiperazin-4-yl-propyl-1,1phosphonic acid (±CPP) depressed activity of ILS, but not ISS, mice. No strain differences were observed in spontaneous alternations or in the number or affinity of NMDARs in the brain regions examined. Likewise, the magnitudes of hippocampal NMDAR-mediated fEPSPs were similar in ILS and ISS mice and were inhibited to the same extent by a competitive NMDAR antagonist. However, both ethanol and the NMDAR NR2B receptor antagonist ifenprodil inhibited the late component of hippocampal NMDAR fEPSPs to a greater extent in ISS, than in ILS, mice. Conclusions: Differential ethanol- and MK-801-induced behavioral activation in ILS and ISS mice was not associated with differences in NMDAR number. Nonetheless, pharmacological differences in hippocampal NMDAR responsiveness suggest that ISS mice express NMDARs that have a greater sensitivity to noncompetitive, but not competitive, NMDAR antagonists. These differences, which may reflect differences in NMDAR subunit composition, could underlie the differential responsiveness to low doses of ethanol in ILS and ISS mice. [source] Excitatory synaptic potentials in spastic human motoneurons have a short rise-timeMUSCLE AND NERVE, Issue 1 2005Nina L. Suresh PhD Abstract This study assessed whether changes in size or time-course of excitatory postsynaptic potentials (EPSPs) in motoneurons innervating spastic muscle could induce a greater synaptic response, and thereby contribute to reflex hyperexcitability. We compared motor unit (MU) firing patterns elicited by tendon taps applied to both spastic and contralateral (nonspastic) biceps brachii muscle in hemiparetic stroke subjects. Based on recordings of 115 MUs, significantly shortened EPSP rise times were present on the spastic side, but with no significant differences in estimated EPSP amplitude. These changes may contribute to hyperexcitable reflex responses at short latency, but the EPSP amplitude changes appear insufficient to account for global differences in reflex excitability. Muscle Nerve, 2005 [source] Presynaptic modulation of cholinergic and non-cholinergic fast synaptic transmission in the myenteric plexus of guinea pig ileumNEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2004K. J. LePard Abstract, These studies investigated receptors modulating release of mediators of fast excitatory postsynaptic potentials (fEPSPs) in guinea pig ileum myenteric plexus using electrophysiological methods. Fast EPSPs inhibited by >95% by hexamethonium (100 ,mol L,1) were cholinergic; mixed fEPSPs were inhibited <95% by hexamethonium. Non-cholinergic fEPSPs were studied in the presence of hexamethonium. The ,2-adrenergic receptor agonist UK 14304 inhibited cholinergic (maximum inhibition = 76%, EC50 = 18 nmol L,1), mixed (81%, 21 nmol L,1) and non-cholinergic (76%, 44 nmol L,1) fEPSPs equally. The 5-HT1 receptor agonist 5-carboxamidotryptamine inhibited cholinergic, mixed and non-cholinergic fEPSPs equally. Renzapride, increased non-cholinergic (33%) less than mixed (97%, 13 ,mol L,1) fEPSPs. Renzapride inhibited the purely cholinergic fEPSPs (,29%) but potentiated the cholinergic component of mixed fEPSPs (39%). Prucalopride potentiated all fEPSPs equally (30,33%). 5-HT (0.1 ,mol L,1) induced potentiation of cholinergic (75%), mixed (97%) and non-cholinergic (84%) fEPSPs was not statistically different. The potentiating effects of renzapride and 5-HT on fEPSPs were inhibited by the 5-HT4 receptor antagonist, SB 204070 (10 nmol L,1). Renzapride (0.3 ,mol L,1) blocked 5-HT-induced increases in cholinergic fEPSPs. ,2-Adrenergic and 5-HT1 receptors mediate inhibition of transmitter release from cholinergic and mixed terminals. 5-HT and prucalopride, acting at 5-HT4 receptors, facilitate all fEPSPs; renzapride facilitates the cholinergic and non-cholinergic components of mixed fEPSPs but not purely cholinergic fEPSPs. Cholinergic synapses may express few 5-HT4 receptors or a renzapride-insensitive 5-HT4 receptor isoform. [source] Frequency processing at consecutive levels in the auditory system of bush crickets (tettigoniidae)THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 15 2010Tim Daniel Ostrowski Abstract We asked how processing of male signals in the auditory pathway of the bush cricket Ancistrura nigrovittata (Phaneropterinae, Tettigoniidae) changes from the ear to the brain. From 37 sensory neurons in the crista acustica single elements (cells 8 or 9) have frequency tuning corresponding closely to the behavioral tuning of the females. Nevertheless, one-quarter of sensory neurons (approximately cells 9 to 18) excite the ascending neuron 1 (AN1), which is best tuned to the male's song carrier frequency. AN1 receives frequency-dependent inhibition, reducing sensitivity especially in the ultrasound. When recorded in the brain, AN1 shows slightly lower overall activity than when recorded in the prothoracic ganglion close to the spike-generating zone. This difference is significant in the ultrasonic range. The first identified local brain neuron in a bush cricket (LBN1) is described. Its dendrites overlap with some of AN1-terminations in the brain. Its frequency tuning and intensity dependence strongly suggest a direct postsynaptic connection to AN1. Spiking in LBN1 is only elicited after summation of excitatory postsynaptic potentials evoked by individual AN1-action potentials. This serves a filtering mechanism that reduces the sensitivity of LBN1 and also its responsiveness to ultrasound as compared to AN1. Consequently, spike latencies of LBN1 are long (>30 ms) despite its being a second-order interneuron. Additionally, LBN1 receives frequency-specific inhibition, most likely further reducing its responses to ultrasound. This demonstrates that frequency-specific inhibition is redundant in two directly connected interneurons on subsequent levels in the auditory system. J. Comp. Neurol. 518:3101,3116, 2010. © 2010 Wiley-Liss, Inc. [source] Excitatory synaptic inputs on myenteric Dogiel type II neurones of the pig ileumTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 2 2001Wim Cornelissen Abstract The synaptic input on myenteric Dogiel type II neurones (n = 63) obtained from the ileum of 17 pigs was studied by intracellular recording. In 77% of the neurones, electrical stimulation of a fibre tract evoked fast excitatory postsynaptic potentials (fEPSPs) with an amplitude of 6 ± 5 mV (mean ± S.D.) and lasting 49 ± 29 ms. The nicotinic nature of the fEPSPs was demonstrated by superfusing hexamethonium (20 ,M). High-frequency stimulation (up to 20 Hz, 3 seconds) did not result in a rundown of the fEPSPs, and did not evoke slow excitatory or inhibitory postsynaptic potentials. The effects of neurotransmitters, possibly involved in these excitatory responses, were investigated. Pressure microejection of acetylcholine (10 mM in pipette) resulted in a fast nicotinic depolarisation in 67%(18/27) of the neurones (13 ± 9 mV, duration 7.0 ± 7.2 seconds) as did 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) application (10 mM; 14 ± 10 mV, duration 4.1 ± 2.8 seconds) in 76%of the cells. The fast nicotinic response to acetylcholine was sometimes (6/27) followed by a slow muscarinic depolarisation (8 ± 4 mV; duration 38.7 ± 10.8 seconds). Immunostaining revealed 5-hydroxytryptamine hydrochloride (5-HT)- and calcitonin gene-related peptide (CGRP)-positive neuronal baskets distributed around and in close vicinity to Dogiel type II neuronal cell bodies. Microejection of 5-HT (10 mM) resulted in a fast nicotinic-like depolarisation (12 ± 6 mV, duration 3.0 ± 1.3 seconds) in 4 of 8 neurones tested, whereas microejection of CGRP (20 mM) gave rise to a slow muscarinic-like depolarisation (6 ± 2 mV, duration 56.0 ± 27.5 seconds) in 8 of 12 neurones tested. In conclusion, myenteric Dogiel type II neurones in the porcine ileum receive diverse synaptic input. Mainly with regard to the prominent presence of nicotinic responses, these neurones behave contrary to their guinea pig counterparts. J. Comp. Neurol. 432:137,154, 2001. © 2001 Wiley-Liss, Inc. [source] Ganglionic transmission in a vasomotor pathway studied in vivoTHE JOURNAL OF PHYSIOLOGY, Issue 9 2010Bradford Bratton Intracellular recordings were made in vivo from 40 spontaneously active cells in the third lumbar sympathetic ganglion of urethane-anaesthetized rats. In 38/40 cells ongoing action potentials showed strong cardiac rhythmicity (93.4 ± 1.9% modulation) indicating high barosensitivity and probable muscle vasoconstrictor (MVC) function. Subthreshold excitatory postsynaptic potentials (EPSPs) showed the same pattern. The 38 barosensitive neurons fired action potentials at 2.9 ± 0.3 Hz. All action potentials were triggered by EPSPs, most of which were unitary events. Calculations indicated that <5% of action potentials were triggered by summation of otherwise subthreshold EPSPs. ,Dominant' synaptic inputs with a high safety factor were identified, confirming previous work. These were active in 24/38 cells and accounted for 32% of all action potentials; other (,secondary') inputs drove the remainder. Inputs (21 dominant, 19 secondary) attributed to single preganglionic neurons fired at 1.38 ± 0.16 Hz. An average of two to three preganglionic neurons were estimated to drive each ganglion cell's action potentials. When cells were held hyperpolarized to block spiking, a range of spontaneous EPSP amplitudes was revealed. Threshold equivalent was defined as the membrane potential value that was exceeded by spontaneous EPSPs at the same frequency as the cell's original firing rate. In 10/12 cells examined, a continuum of EPSP amplitudes overlapped threshold equivalent. Small changes in cell excitability could therefore raise or lower the percentage of preganglionic inputs triggering action potentials. The results indicate that vasoconstrictor ganglion cells in vivo mostly behave not as 1:1 relays, but as continuously variable gates. [source] | |||||||||||||