Tetanic Potentiation Research Articles

Site-Specific Emulation of Neuronal Synaptic Behavior in Au Nanoparticle-Decorated Self-Organized TiOx Surface.

Neuromorphic computing is a potential approach for imitating massive parallel processing capabilities of a bio-synapse. To date, memristors have emerged as the most appropriate device for designing artificial synapses for this purpose due to their excellent analog switching capacities with high endurance and retention. However, to build an operational neuromorphic platform capable of processing high-density information, memristive synapses with nanoscale footprint are important, albeit with device size scaled down, retaining analog plasticity and low power requirement often become a challenge. This paper demonstrates site-selective self-assembly of Au nanoparticles on a patterned TiOx layer formed as a result of ion-induced self-organization, resulting in site-specific resistive switching and emulation of bio-synaptic behavior (e.g., potentiation, depression, spike rate-dependent and spike timing-dependent plasticity, paired pulse facilitation, and post tetanic potentiation) at nanoscale. The use of local probe-based methods enables nanoscale probing on the anisotropic films. With the help of various microscopic and spectroscopic analytical tools, the observed results are attributed to defect migration and self-assembly of implanted Au atoms on self-organized TiOx surfaces. By leveraging the site-selective evolution of gold-nanostructures, the functionalized TiOx surface holds significant potential in a multitude of fields for developing cutting-edge neuromorphic computing platforms and Au-based biosensors with high-density integration.

Микроэлектрофизиологическое изучение соотношения возбудительных и тормозных синаптических процессов в кортиконигральной проекции к SNс на модели болезни Паркинсона

In series experiments on 9 Albino rats (250 g) the comparative analyses of single neuron’s impulse activity of Substantia nigra compacta – SNc at high frequency stimulation (HFS) of the brain primary motor cortex (M1) in norm (107 neurons, n=4) and on the model of Parkison’s disease (PD) (105 neurons, n=5) has been conducted. Analyses of relative degree of depressor and excitatory effects frequency intensity on the base of spikes average frequency diagrams, represented as a disc diagram (in %) resulted in the following conclusions. In SNc neurons on the model of PD the poststimulus manifestations of depressor activity completely absent, but tetanic potentiation in both sequences 1,65- and 2,02-multiple exceeded of those in the norm. The comparative analyses of pre- and poststimulus frequency activity of SNc neurons on the model of PD, led to the conclusion that it is considerably higher in comparison with the norm. It has been revealed vulnerability of depressor poststimulus effects of SNc neurons, even their full absence, that in its turn, testifies about more involvement of SNc in PD.

Plasticity in Motoneurons Following Spinal Cord Injury in Fructose-induced Diabetic Rats.

Spinal cord injury (SCI) causes motor impairment and the proper excitation/inhibition balance in motoneurons is important for recovery. Diabetes mellitus impairs regenerative capacity following SCI. The purpose of this study was to assess the short-term plasticity (STP) of lumbar spinal cord motoneurons in conditions of (1) lateral hemisection (SCI), (2) fructose-induced diabetes (D), and (3) diabetes associated with hemisection (D + SCI). We show that in the cases of SCI, D, and D + SCI, the ratio of percentage share of excitatory and inhibitory combinations of motoneurons responses to high-frequence stimulation of sciatic nerve is multidirectional. In the SCI and D + SCI groups, the cumulative changes in generalized baseline frequencies decreased significantly. When we compared the cumulative changes in the intensity of excitatory and inhibitory responses relative to baseline during high-frequency stimulation (tetanization epoch), we found that there was a significant intensification in tetanic depression in the D + SCI groups versus SCI, as well as an intensification in tetanic potentiation in the D + SCI vs. D and D + SCI vs. SCI groups. Thus, in conditions of traumatic and/or metabolic pathology, the distinct synaptic inputs exhibit opposing plasticity for homeostatic control of neurotransmission and these integral changes most likely shape postsynaptic STP in the spinal motor network.

Microelectrophysiological Studies of the Ratio of Excitatory to Inhibitory Synaptic Processes in the Corticonigral Projection in a Model of Parkinson’s

Experiments on 23 white male rats (250 g) analyzed the spike activity of individual neurons in the substantia nigra pars compacta (SNc, 242 neurons, n = 11) and substantia nigra pars reticulata (SNr, 289 neurons, n = 12) during high-frequency stimulation of the primary motor cortex (M1)in normal animals and in animals with a rotenone model of Parkinson’s disease (BP). SNc neurons in the model of PD showed a complete absence of depressor effects induced by stimulation, though tetanic potentiation was accompanied by posttetanic potentiation and depression at levels 1.65 and 2.02 times greater than in normal animals. In SNr neurons in normal animals, tetanic potentiation, accompanied by post-tetanic potentiation and depression, was 2.37 times greater than tetanic depression, while in the model of PD the levels of both depressor and excitatory activity induced by stimulation were below normal. Spike activity frequency in SNc and SNr neurons preceding and accompanying stimulation was significantly greater than normal in the model of PD. This is evidence for excitotoxicity accompanying neurodegenerative damage, which is completed by neuron apoptosis and death. In SNr neurons, both depressor and excitatory reactions accompanying stimulation were markedly dominant over those in SNc neurons, which is evidence for more extensive cortical projections to the SNr. Furthermore, SNc neurons demonstrated greater susceptibility to pathological changes due to poststimulus depressor effects than SNr neurons, with formation of more marked excitatory effects, which is evidence of a greater involvement of the SNc in PD. In the model of PD, lacking stimulation-induced depressor effects and more marked excitatory effects in SNc neurons, SNr neurons retained their depressor reactions and relatively decreased excitatory reactions, which is evidence of a lower level of susceptibility of SNr neurons to excitotoxicity, extreme increases in the excitability of surviving neurons compensating for the lack of excitation of dead cells.

Микроэлектрофизиологическое изучение соотношения возбудительных и тормозных синаптических процессов в кортико-нигральной проекции на модели болезни Паркинсона

The impulse activity of single neurons in substantia nigra pars compacta - SNc (242 neurons, n=11) and substantia nigra pars reticulate - SNr (289 neurons, n=12) under high frequency stimulation of primary motor cortex (M1) was analyzed on 23 white male rats in control and rotenone model of Parkinson’s disease (PD). In SNc neurons in PD model there was no stimulation-induced depression, however, the posttetatic potentiation and depression following the tetanic potentiation, were 1.65 and 2.02 times higher than in control. In control SNr neurons the tetanic potentiation followed by the posttetanic potentiation and depression was 2.37 times higher than the tetanic depression, whereas in the PD model both depression and potentiation levels were subnormal. In PD model, both SNc and SNr neurons exhibited significantly higher spike frequency before and during the stimulation in comparison with control. This indicates the presence of the excitotoxicity accompanied by the neurodegenerative damage followed by the apoptosis and the neuronal death. In SNr neurons both depression and potentiation after the stimulation were much more prominent than in SNc neurons, which indicates that the cortical projections on the SNr are more pronounced. Moreover, the SNc neurons demonstrated higher succeptibility to the pathological changes in the poststimulus depression, leading to the more pronounced potentiation in those neurons in comparison with the SNr neurons, which indicates the more prominent involvement of the former in the PD pathogenesis. In the PD model, with no stimulation-induced depression and more prominent potentiation in the SNc neurons, the SNr neurons maintain the depression and show relatively lowered potentiation, which indicates their lower succeptibility to the excitotoxicity, and the excessive excitability of the remaining neurons as a compensation for the dead ones.

A Study of Synaptic Plasticity in the Rat Hippocampal Field CA1 in Conditions of Deficiency of Acetylcholine and Other Neurotransmitters

Experiments showed that high-amplitude, long-lasting tetanic potentiation could be induced in synaptic terminals formed by Schaffer collaterals on field CA1 pyramidal cells in rat hippocampal slices in which acetylcholine deficiency was modeled by application of the choline reuptake inhibitor hemicholine and the vesicular acetylcholine uptake inhibitor vesamicol. Deficiencies of different neurotransmitters were modeled by 5-min incubation of slices in solution containing an elevated potassium concentration, which led, as demonstrated previously, to depletion of the release of these neurotransmitters from nerve endings. The result of this procedure was that synapses formed by Schaffer collaterals developed long-term potentiation. Long-term post-tetanic potentiation was also induced in slices on this background in the model of neurotransmitter deficiency. Its amplitude was not significantly different from the amplitude of long-term potentiation in controls but was less than that obtained using vesamicol or hemicholine. As deficiency of serotonin, noradrenaline, and dopamine is known to be able to decrease the extent of long-term potentiation of synaptic transmission between fields CA3 and CA1, these result points to the possibility that acetylcholine deficiency partially compensates for this decrease. Considering known data on the locations of different types of nicotinic and muscarinic cholinoreceptors both on pyramidal cells and on inhibitory interneurons, the possible effects of acetylcholine on the efficiency of the inputs formed by Schaffer collaterals were studied. This analysis and consideration of the data obtained here led to the hypothesis that in conditions of acetylcholine deficiency, the main influence on the efficiency of excitation of pyramidal cells in field CA1 by field CA3 is exerted by disinhibition via a network of interacting interneurons.

Systemic LPS resulted in a transient hippocampus malfunction but a prolonged corpus callosum injury

BackgroundTo investigate the effect of systemic lipopolysaccharide (LPS) on function of hippocampus and corpus callosum (CC) in adult rats.MethodsAdult rats with mature white matter tract were divided into systemic LPS and saline injection groups. Animal were euthanized following 3 daily injections (day 3) and 3-day after cessation of injections (day 6). At both time points, hippocampal long term potentiation (LTP) and CC compound action potentials (CAP) were recorded, beta amyloid precursor protein (β-APP) level in CC tissue was measured by Western blot, and microglia activation was examined by immunostaining and proportional area analysis.ResultsSystemic LPS significantly decreased amplitude of both post tetanic potentiation (PTP) and LTP at day 3, but PTP and LTP turned to be normal at day 6. CAP was significantly declined at day 3 but was further declined at day 6. The β-APP levels in CC tissues of LPS injected rats were significantly higher than that of saline group at both time-points. Interestingly, proportional area measurement disclosed that microglial areas in both hippocampus and CC significantly expanded at day3, but at the day 6, microglial area decreased in hippocampus but further increased in CC.ConclusionSystemic LPS resulted in a transient hippocampus malfunction but a prolonged CC injury. Microglia activation may correlate with such LPS induced white matter injury.

Morphofunctional Correlation of Excitatory and Depressor Synaptic Processes in Hippocampus, Amygdala and Basal Meynert Nucleus Neurons in Dynamics of Development of Alzheimer's Disease Model Induced by Aβ25-35

Objective: Compensatory mechanisms are responsible for the clinical signs of suppression of neurodegeneration. Intervention into their mechanisms on an example of the ratio of excitatory and depressor synaptic responses will contribute to the development of therapeutic strategies.Methods: After 12-28 weeks (w) of experiment on the model of Alzheimer’s disease (AD), an activity of single neurons of hippocampus (H), Amygdala (Am) and, nucleus basalis of Meynert (NBM) to high frequency stimulation (HFS) of entorhinal cortex (EC) was recorded. The high frequency stimulation of H resulted in an activity of single neurons of the Am and NBM. By means of on-line selection and special mathematical analysis, tetanic potentiation (TP) and depression (TD) with further combination into posttetanic uni and multidirectional sequences, were revealed. In morpho- and histochemical study, the method of revelation of Сa2+- dependent phosphorylation was used.Results: After 12 weeks of experiment on the model of AD, a heavy TD of NBM and Аm neurons to HFS of H, as well as a weak (TD) in H and NBM neurons to HFS of EC were found. TP occurred by the activation of ЕС in the H (TP PTP) and in Am (TP PTD) neurons, equal to and above the norm in neurons of Am to HFS of H. In the neurons of NBM to HFS of EC, the weakest excitation to HFS of H was detected. In the neurons H to HFS of EC, Am and NBM to HFS of H, after 13-28 weeks, TD and tetanic excitation in all cases were low, which indicating on depletion of compensatory opportunities. Morpho- and histo-chemical changes of H, Am and NBM neurons on the model of AD were characterized by total tendency to structural-metabolic dysfunctions, with distortion of forms, central chromatolysis, presence of light ectopic nucleus with increased nucleolus, change reaction of neurofibrills, lack of reaction processes, accumulation of hyper phosphorylated entities and, presence of spaces with the lack of cellular reaction.Conclusion: The absence of expressed depression, presupposed by us as a protector in the present study, makes it necessary to involve pharmacological interventions with a view to its strengthening, and therefore is the subject of the next reports. Electrophysiological data have been confirmed morphologically.

Protective effects of hydroponic Teucrium polium on hippocampal neurodegeneration in ovariectomized rats.

BackgroundThe hippocampus is a target of ovarian hormones, and is necessary for memory. Ovarian hormone loss is associated with a progressive reduction in synaptic strength and dendritic spine. Teucrium polium has beneficial effects on learning and memory. However, it remains unknown whether Teucrium polium ameliorates hippocampal cells spike activity and morphological impairments induced by estrogen deficiency.MethodsIn the present study, we investigated the effects of hydroponic Teucrium polium on hippocampal neuronal activity and morpho-histochemistry of bilateral ovariectomized (OVX) rats. Tetanic potentiation or depression with posttetanic potentiation and depression was recorded extracellularly in response to ipsilateral entorhinal cortex high frequency stimulation. In morpho-histochemical study revealing of the activity of Ca2+-dependent acid phosphatase was observed. In all groups (sham-operated, sham + Teucrium polium, OVX, OVX + Teucrium polium), most recorded hippocampal neurons at HFS of entorhinal cortex showed TD-PTP responses.ResultsAfter 8 weeks in OVX group an anomalous evoked spike activity was detected (a high percentage of typical areactive units). In OVX + Teucrium polium group a synaptic activity was revealed, indicating prevention OVX-induced degenerative alterations: balance of types of responses was close to norm and areactive units were not recorded. All recorded neurons in sham + Teucrium polium group were characterized by the highest mean frequency background and poststimulus activity. In OVX+ Teucrium polium group the hippocampal cells had recovered their size and shape in CA1 and CA3 field compared with OVX group where hippocampal cells were characterized by a sharp drop in phosphatase activity and there was a complete lack of processes reaction.ConclusionThus, Teucrium polium reduced OVX-induce neurodegenerative alterations in entorhinal cortex-hippocamp circuitry and facilitated neuronal survival by modulating activity of neurotransmitters and network plasticity.

Effects of Stimulation of the Hypothalamic Nuclei on Neurons in the Inferior Vestibular Nucleus after Prolonged Vibration and Administration of Proline-Rich Peptide 1

Impairments to vestibular function after exposure to vibration are to a significant extent due to adaptive-adjustment changes in neurotransmitter processes, which can be regulated by endogenous factors, particularly hypothalamic proline-rich peptide. Studies in Albino rats addressed the synaptic activity of individual neurons in the inferior vestibular nucleus in conditions of high-frequency stimulation of the paraventricular and supraoptic nuclei of the hypothalamus on exposure to vibration and systemic administration of proline-rich peptide 1. The poststimulus spike activity of neurons in the inferior vestibular nucleus in normal conditions was apparent mainly in the form of tetanic potentiation, while activity after vibration was apparent as post-tetanic potentiation. The combination of vibration and use of proline-rich peptide 1 restored the normal balance of excitatory and inhibitory poststimulus reactions and increased the level of excitability of neurons in the inferior vestibular nucleus.

Synaptic Metaplasticity Underlies Tetanic Potentiation in Lymnaea: A Novel Paradigm

We present a mathematical model that explains and interprets a novel form of short-term potentiation, which was found to be use-, but not time-dependent, in experiments done on Lymnaea neurons. The high degree of potentiation is explained using a model of synaptic metaplasticity, while the use-dependence (which is critically reliant on the presence of kinase in the experiment) is explained using a model of a stochastic and bistable biological switch.

LAMBERT–EATON MYASTHENIC SYNDROME–RESULTS FROM THE BNSU SURVEY

Lambert–Eaton myasthenic syndrome (LEMS) is an autoimmune, presynaptic disorder of neuromuscular transmission characterised by proximal limb weakness, autonomic disturbance and depressed tendon reflexes with post–tetanic potentiation. Approximately 50% of patients...

Cortical Presynaptic Control of Dorsal Horn C–Afferents in the Rat

Lamina 5 sensorimotor cortex pyramidal neurons project to the spinal cord, participating in the modulation of several modalities of information transmission. A well-studied mechanism by which the corticospinal projection modulates sensory information is primary afferent depolarization, which has been characterized in fast muscular and cutaneous, but not in slow-conducting nociceptive skin afferents. Here we investigated whether the inhibition of nociceptive sensory information, produced by activation of the sensorimotor cortex, involves a direct presynaptic modulation of C primary afferents. In anaesthetized male Wistar rats, we analyzed the effects of sensorimotor cortex activation on post tetanic potentiation (PTP) and the paired pulse ratio (PPR) of dorsal horn field potentials evoked by C–fiber stimulation in the sural (SU) and sciatic (SC) nerves. We also explored the time course of the excitability changes in nociceptive afferents produced by cortical stimulation. We observed that the development of PTP was completely blocked when C-fiber tetanic stimulation was paired with cortex stimulation. In addition, sensorimotor cortex activation by topical administration of bicuculline (BIC) produced a reduction in the amplitude of C–fiber responses, as well as an increase in the PPR. Furthermore, increases in the intraspinal excitability of slow-conducting fiber terminals, produced by sensorimotor cortex stimulation, were indicative of primary afferent depolarization. Topical administration of BIC in the spinal cord blocked the inhibition of C–fiber neuronal responses produced by cortical stimulation. Dorsal horn neurons responding to sensorimotor cortex stimulation also exhibited a peripheral receptive field and responded to stimulation of fast cutaneous myelinated fibers. Our results suggest that corticospinal inhibition of nociceptive responses is due in part to a modulation of the excitability of primary C–fibers by means of GABAergic inhibitory interneurons.

Medial and lateral perforant path evoked potentials are selectively modulated by pairing with glutamatergic activation of locus coeruleus in the dentate gyrus of the anesthetized rat

Norepinephrine (NE) in vitro produces long-lasting potentiation of medial perforant path input and depression of lateral perforant path input to dentate gyrus in the rat. Similar, but highly transient, effects have been reported in vivo using paragigantocellular stimulation to release NE. The present study uses alternate stimulation of the medial perforant path and lateral olfactory tract (eliciting a lateral perforant path-evoked potential) to examine the effects of glutamatergic activation of locus coeruleus (LC) on the two pathways for up to 3 h post-LC activation. In the first experiment, the expected potentiation of the medial perforant path population spike in dentate gyrus was observed, but without accompanying depression of the lateral perforant path-mediated evoked potential (lateral olfactory tract stimulation, 60 s ISI). In a second experiment, with more frequent pairing of input with NE release (10 s ISI), significant potentiation of lateral perforant path-mediated input to dentate gyrus occurred, but potentiation of medial perforant path input was not seen. A third experiment with a 30 s ISI again produced potentiation of lateral perforant path-mediated input without potentiation of the medial perforant path population spike. The size of effects with the 30 s ISI was intermediate between that seen with 10 s and 60 s ISI. Potentiation of lateral perforant path over medial perforant path input has previously been reported with acute nicotinic activation of the LC. This outcome also resembles heterosynaptic modulation previously reported with tetanic potentiation. The data argue for a competitive relationship between medial and lateral perforant path inputs to dentate gyrus and suggest pairing with increased NE produces a bias favoring one or the other pathway depending on parameters such as strength and frequency. NE potentiating effects on lateral perforant path input here may also have occurred in entorhinal cortex (EC) given the system-wide NE release with LC activation.

Effects of stimulation of the hypothalamic nuclei and treatment with a proline-rich peptide on neurons of the superior vestibular nuclei during exposure to vibration

Vibration impairs functioning of the nervous, cardiovascular, and motor systems. Postvibration disturbances in vestibular function are determined by adaptive changes in neuromediatory processes. We studied the possibility of the regulation of the CNS functions by neurohumoral factors, viz., hypothalamic proline-rich peptides (PRP). We found changes in the spiking activity of single neurons of the superior vestibular nucleus (SVN) in response to high-frequency stimulation (HFS) of the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus in the presence of vibration or systemic treatment with PRP-1. Mathematical analysis of impulse activity showed predominantly tetanic potentiation (TP) in the SVN neurons in response to HFS. Vibration resulted in a decrease in the TP level and an increase in the post-tetanic potentiation. The results of the morphological and histochemical analyses suggest a close relationship between neurons and gliocytes, with both being involved in integral unit formation. An enhanced level of survival of SVN neurons and activation of acidic phosphatase in SVN were also found in the presence of PRP during long-term exposure to vibration.

Polyneuronal Innervation of Single Muscle Fibers in Cat Eye Muscle: Inferior Oblique

Single muscle fibers with multiple axonal endplates (multiply innervated fibers) are normally present in adult extraocular muscles (EOMs), while most other mammalian skeletal muscles contain fibers with a single myoneural junction. Recent findings by others led us to investigate for the presence of polyneuronal innervation (innervation of a single muscle fiber by >1 motoneuron) in the inferior oblique (IO) muscle of pentobarbital anesthetized cats. The IO muscle nerve branches, as they coursed through the orbit, were further divided for independent or simultaneous electrical stimulation with bipolar electrodes. Four of five established tests for polyneuronal innervation gave positive results. The sum of the twitch (1) and tetanic (2) tensions in response to individual nerve branch stimulation was greater than that for simultaneous (whole) nerve stimulation. The summed electromyographic (EMG) responses (3) gave a similar positive result. The result for crossed tetanic potentiation (4) was negative for polyneuronal innervation while the crossed fatigue (5) test was positive. These results are consistent with recent studies. That the EOMs exhibit polyneuronal innervation further explains the eye-movement system's functional integrity during some neuromuscular disorders as well as its ability to operate with precision after the loss of numerous motoneurons.

Synaptic organization and input‐specific short‐term plasticity in anterior cingulate cortical neurons with intact thalamic inputs

The absence of a slice preparation with intact thalamocortical pathways has held back elucidation of the cellular and synaptic mechanisms by which thalamic signals are differentially transmitted to and processed in the anterior cingulate cortex (ACC). In this report we introduce an innovative mouse brain slice preparation in which it is possible to explore the electrophysiological properties of ACC neurons with intact long-distance inputs from medial thalamic (MT) nuclei by intracellular recordings; this MT-ACC neuronal pathway plays an integral role in information transmission. Biocytin-labeled fibers in a functional slice could be traced anterogradely or retrogradely from the MT via the reticular thalamic nuclei, striatum and corpus callosum to the cingulate cortical areas. Eighty-seven cells downstream of the thalamic projections in 49 slices were recorded intracellularly. Intracellular recordings in the ACC showed that thalamocingulate transmission involves both alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate and N-methyl-D-aspartate (NMDA) subtypes of glutamate receptors. Thalamus-evoked responses recorded extracellularly in the ACC were activated and progressed along a deep-superficial-deep trajectory loop across the ACC layers. We observed enhanced paired-pulse facilitation and tetanic potentiation of thalamocingulate synapses, suggestive of input-specific ACC plasticity and selective processing of information relayed by thalamocingulate pathways. Furthermore, we observed differential responses of ACC neurons to thalamic burst stimulation, which underscores the importance of MT afferents in relaying sensory information to the ACC. This new slice preparation enables the contribution of MT-evoked ACC synaptic transmission to short-term plasticity in the neuronal circuitry underlying sensory information processing to be examined in detail.

Tetanic potentiation in motor units of rat medial gastrocnemius

Tetanic potentiation is a phenomenon, which expresses the ability of a motor unit (MU) to increase its force output in tetanic contractions above that predicted with an assumption of algebraic summation of single twitch responses. To quantify tetanic potentiation, a coefficient TPC (tetanic potentiation coefficient) was defined as a ratio of the areas below tetanic force recording corresponding to the single stimulus contribution and that of the single twitch. Single MUs (27 Slow, 71 Fast, Fatigue Resistant, and 47 Fast, Fatigable) were isolated from the rat medial gastrocnemius muscle (MG) by ventral root splitting. TPC value was rate-dependent, with the maximum TPCmax at a certain optimal rate. The largest values of the TPCmax were obtained in the weakest and most fatigue resistant (S and weak FR) MUs. The different manifestation of staircase effect, post-tetanic and tetanic potentiation in individual MU types indicates that these phenomena may be independent of each other. We suggest that these phenomena as well as the fatigue resistance should be reexamined with protocols adjusted to the MU optimal frequency. Correspondence should be addressed to M. Piotrkiewicz, Email: masia@ibib.waw.pl

Parallel Pre- and Postsynaptic Pathways to Puncta and Potentiation?

N -methyl-D-aspartate-type glutamate receptor (NMDAR)-dependent long-term potentiation (LTP) of synaptic efficacy appears to involve early microstructural changes in which pre- and postsynaptic proteins aggregate into clusters (or puncta). Wang et al. used a combination of pharmacological analysis, immunocytochemistry, and electrophysiology in dissociated cultures of rat hippocampal neurons to investigate the signaling pathways that mediate glutamate-dependent development of pre- and postsynaptic puncta and long-lasting glutamate-dependent enhancement of synaptic communication in cultured neurons (long-lasting potentiation) and found evidence implicating a nitric oxide (NO), guanosine 3′,5′-monophosphate (cGMP), and cGMP-dependent protein kinase (cGK) pathway. Immunocytochemical analysis further revealed that cGK1 and VASP (vasodilator-stimulated phosphoprotein, which is a substrate for cGK that is involved in the regulation of the actin cytoskeleton) were localized at both pre- and postsynaptic sites and that glutamate stimulated an increase in VASP phosphorylation at the cGK site. Pharmacological analysis implicated actin in glutamate-dependent increases in miniature excitatory postsynaptic current (mEPSC) frequency, and experiments in which glutamate-dependent increases in EPSC amplitude in cultured neurons were measured implicated both pre- and postsynaptic actin in the response. Long-lasting potentiation of mEPSC frequency and glutamate-dependent increases in pre- and postsynaptic puncta involved Rho GTPases and Rho kinase (ROCK), and experiments measuring tetanic stimulation-dependent potentiation of the EPSC between individual neurons in culture indicated that both pre- and postsynaptic RhoA were involved. RhoA and ROCK appeared to act both in parallel with the NO-cGMP-cGK-VASP pathway in regulating actin, and also upstream of cGMP. H.-G. Wang, F.-M. Lu, I. Jin, H. Udo, E. R. Kandel, J. de Vente, U. Walter, S. M. Lohmann, R. D. Hawkins, I. Antonova, Presynaptic and postsynaptic roles of NO, cGK, and RhoA in long-lasting potentiation of and aggregation of synaptic proteins. Neuron 45 , 389-403 (2005). [PubMed]

Plasticidad sináptica a corto plazo

At many chemical synapses, the amount of transmitter released by each action potential can increase or decrease markedly after the onset of specific temporal patterns of activity.This review focuses on mechanisms and functions of short term presynaptic plasticity that last from milliseconds to minutes. The short term enhancement of neurotransmitter release is due to three calcium dependent presynaptic processes differing in their durations: about one second or less (facilitation), about 30 seconds (augmentation) and several minutes (post tetanic potentiation). These forms of short term potentiation are usually attributed to a transient elevation in presynaptic calcium ions (Ca2+) concentration following the arrival of the action potential. Otherwise, presynaptic depression processes, as well as the facilitation ones, depend on neurotransmitter release probability. Thus, synapses with high release probability show few facilitation and are easily depressed because of their ability to deplete faster all synaptic vesicles of the ready releasable pool.Short term synaptic plasticity appears to serve as a flexible mechanism for temporal information processing in higher cortical integration.