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1.
Vesicular zinc (Zn(2+)) is found in a subset of glutamatergic nerve terminals throughout the mammalian forebrain and is colocalized with glutamate. Despite well-documented neuromodulatory roles, exocytosis of endogenous Zn(2+) from presynaptic terminals has never been directly demonstrated, because existing studies have measured elevated Zn(2+) concentrations by examining the perfusate. Thus, the specific origin of synaptic Zn(2+) remains a controversial subject. Here, we describe synaptic Zn(2+) trafficking between cellular compartments at hippocampal mossy fiber synapses by using the fluorescent indicator Zinpyr-1 to label the hippocampal mossy fiber boutons. We determined endogenous Zn(2+) exocytosis by direct observation of vesicular Zn(2+) as decreasing fluorescence intensity from presynaptic axonal boutons in the stratum lucidum of CA3 during neural activities induced by the stimulation of membrane depolarization. This presynaptic fluorescence gradually returned to a level near baseline after the withdrawal of moderate stimulation, indicating an endogenous mechanism to replenish vesicular Zn(2+). The exocytosis of the synaptic Zn(2+) was also dependent on extracellular Ca(2+) and was sensitive to Zn(2+)-specific chelators. Vesicular Zn(2+) loading was sensitive to the vacuolar-type H(+)-ATPase inhibitor concanamycin A, and our experiments indicated that blockade of vesicular reloading with concanamycin A led to a depletion of that synaptic Zn(2+). Furthermore, synaptic Zn(2+) translocated to the postsynaptic cell body upon release to produce increases in the concentration of weakly bound Zn(2+) within the postsynaptic cytosol, demonstrating a feature unique to ionic substances released during neurotransmission. Our data provide important evidence for Zn(2+) as a substance that undergoes release in a manner similar to common neurotransmitters. 相似文献
2.
Constanze Krohs Christoph Krber Lena Ebbers Faiza Altaf Giulia Hollje Simone Hoppe Yvette Drflinger Haydn M. Prosser Hans Gerd Nothwang 《The Journal of neuroscience》2021,41(32):6796
A point mutation in miR-96 causes non-syndromic progressive peripheral hearing loss and alters structure and physiology of the central auditory system. To gain further insight into the functions of microRNAs (miRNAs) within the central auditory system, we investigated constitutive Mir-183/96dko mice of both sexes. In this mouse model, the genomically clustered miR-183 and miR-96 are constitutively deleted. It shows significantly and specifically reduced volumes of auditory hindbrain nuclei, because of decreases in cell number and soma size. Electrophysiological analysis of the calyx of Held synapse in the medial nucleus of the trapezoid body (MNTB) demonstrated strongly altered synaptic transmission in young-adult mice. We observed an increase in quantal content and readily releasable vesicle pool size in the presynapse while the overall morphology of the calyx was unchanged. Detailed analysis of the active zones (AZs) revealed differences in its molecular composition and synaptic vesicle (SV) distribution. Postsynaptically, altered clustering and increased synaptic abundancy of the AMPA receptor subunit GluA1 was observed resulting in an increase in quantal amplitude. Together, these presynaptic and postsynaptic alterations led to a 2-fold increase of the evoked excitatory postsynaptic currents in MNTB neurons. None of these changes were observed in deaf Cldn14ko mice, confirming an on-site role of miR-183 and miR-96 in the auditory hindbrain. Our data suggest that the Mir-183/96 cluster plays a key role for proper synaptic transmission at the calyx of Held and for the development of the auditory hindbrain.SIGNIFICANCE STATEMENT The calyx of Held is the outstanding model system to study basic synaptic physiology. Yet, genetic factors driving its morphologic and functional maturation are largely unknown. Here, we identify the Mir-183/96 cluster as an important factor to regulate its synaptic strength. Presynaptically, Mir-183/96dko calyces show an increase in release-ready synaptic vesicles (SVs), quantal content and abundance of the proteins Bassoon and Piccolo. Postsynaptically, the quantal size as well as number and size of GluA1 puncta were increased. The two microRNAs (miRNAs) are thus attractive candidates for regulation of synaptic maturation and long-term adaptations to sound levels. Moreover, the different phenotypic outcomes of different types of mutations in the Mir-183 cluster corroborate the requirement of mutation-tailored therapies in patients with hearing loss. 相似文献
3.
Short-term plasticity was investigated at the perforant path-granule cell synapse in the hippocampal slice preparation. A successive decrement in the amplitude of the extracellular EPSP was obtained at all stimulus frequencies above 0.05 Hz. This effect of repetitive stimulation has previously been shown to fulfill the requirements for habituation processes. If each stimulus within an habituation train was followed by a second identical test stimulus the response to the test stimulus was larger than that to the paired conditioning stimulus. This short-term plasticity has been called paired pulse potentiation. The test response potentiated only with respect to the paired conditioning response and not with respect to previous test responses. Neither form of plasticity appeared to result from changes in the amplitude of the afferent fiber volley. Both habituation and paired pulse potentiation result from an interaction of at least three changes in the efficacy of transmission after a conditioning stimulus: (1) an initial depression, (2) an intermediate relative potentiation and (3) a late depression which decays slowly. Paired pulse potentiation could be demonstrated only if the interpair interval corresponded to the period of maximal late depression and the interstimulus interval to the period of relative potentiation. The amplitudes of intermediate relative potentiation and late depression (and inhibition of transmission by 2-amino-4-phosphonobutyric acid (APB)) were inversely related to the control response amplitude. This relationship likely derives from nonlinear stimulation of postsynaptic ionic currents at higher stimulus intensities. In contrast, the initial depression increased with response amplitude. This is consistent with a mechanism dependent on the postsynaptic membrane potential, such as refractoriness to succeeding stimuli. When the response amplitudes in the presence and absence of 2.5 mM APB were equalized by adjusting the stimulus intensity, no difference was found in the magnitude of either form of plasticity. Since APB probably inhibits transmission at this site through competitive antagonism at the postsynaptic receptor, this observation suggests that habituation and paired pulse potentiation are generated presynaptically. 相似文献
4.
Ionotropic glutamate receptor GluA4 and T‐type calcium channel Cav3.1 subunits control key aspects of synaptic transmission at the mouse L5B‐POm giant synapse
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The properties and molecular determinants of synaptic transmission at giant synapses connecting layer 5B (L5B) neurons of the somatosensory cortex (S1) with relay neurons of the posteriomedial nucleus (POm) of the thalamus have not been investigated in mice. We addressed this by using direct electrical stimulation of fluorescently labelled single corticothalamic terminals combined with molecular perturbations and whole‐cell recordings from POm relay neurons. Consistent with their function as drivers, we found large‐amplitude excitatory postsynaptic currents (EPSCs) and multiple postsynaptic action potentials triggered by a single presynaptic action potential. To study the molecular basis of these two features, ionotropic glutamate receptors and low voltage‐gated T‐type calcium channels were probed by virus‐mediated genetic perturbation. Loss of GluA4 almost abolished the EPSC amplitude, strongly delaying the onset of action potential generation, but maintaining the number of action potentials generated per presynaptic action potential. In contrast, knockdown of the Cav3.1 subunit abrogated the driver function of the synapse at a typical resting membrane potential of ?70 mV. However, when depolarizing the membrane potential to ?60 mV, the synapse relayed single action potentials. Hence, GluA4 subunits are required to produce an EPSC sufficiently large to trigger postsynaptic action potentials within a defined time window after the presynaptic action potential, while Cav3.1 expression is essential to establish the driver function of L5B‐POm synapses at hyperpolarized membrane potentials. 相似文献
5.
At the photoreceptor ribbon synapse, glutamate released from vesicles at different positions along the ribbon reaches the same postsynaptic receptors. Thus, vesicles may not exert entirely independent effects. We examined whether responses of salamander retinal horizontal cells evoked by light or direct depolarization during paired recordings could be predicted by summation of individual miniature excitatory postsynaptic currents (mEPSCs). For EPSCs evoked by depolarization of rods or cones, linear convolution of mEPSCs with photoreceptor release functions predicted EPSC waveforms and changes caused by inhibiting glutamate receptor desensitization. A low-affinity glutamate antagonist, kynurenic acid (KynA), preferentially reduced later components of rod-driven EPSCs, suggesting lower levels of glutamate are present during the later sustained component of the EPSC. A glutamate-scavenging enzyme, glutamic-pyruvic transaminase, did not inhibit mEPSCs or the initial component of rod-driven EPSCs, but reduced later components of the EPSC. Inhibiting glutamate uptake with a low concentration of dl -threo-β-benzoyloxyaspartate (TBOA) also did not alter mEPSCs or the initial component of rod-driven EPSCs, but enhanced later components of the EPSC. Low concentrations of TBOA and KynA did not affect the kinetics of fast cone-driven EPSCs. Under both rod- and cone-dominated conditions, light-evoked currents (LECs) were enhanced considerably by TBOA. LECs were more strongly inhibited than EPSCs by KynA, suggesting the presence of lower glutamate levels. Collectively, these results indicate that the initial EPSC component can be largely predicted from a linear sum of individual mEPSCs, but with sustained release, residual amounts of glutamate from multiple vesicles pool together, influencing LECs and later components of EPSCs. 相似文献
6.
Three rhesus monkeys were trained to respond to a given auditory signal, the nature of which could be predicted from a preceding visual stimulus. The activity of 28 units in the auditory cortex and 53 units in the Medial Geniculate Body (MGB) of the monkey was recorded during task-performance conditions, as well as in the non-performance conditions. The activity of about one third of the cortical and MGB units was independent of the behaving status of the animal. In other units, the response to an auditory signal delivered during task-performance conditions as compared to the response recorded during non-performance periods was either augmented or attenuated. Furthermore, it was found that the spontaneous activity of most of the MGB and cortical units was continuously affected by either an excitatory or an inhibitory input, activated by the behavioral state. The temporal characteristics of behavioral modulation were studied by computing an amplification curve for all MGB units characterized by a ‘through stimulus excitation’ type of response. Analysis of these curves together with the behavioral effect on the spontaneous activity allows the suggestion of possible mechanisms by which the behavioral state of the monkey modulates the activity in the thalamocortical segment of the auditory system. 相似文献
7.
The calyx of Held synapse is a giant axosomatic synapse that acts as a fast relay in the sound localization circuit of the brainstem. In rodents it forms within a relatively brief period starting around the second postnatal day (P2). The relative timing of the formation of its pre- and the postsynaptic compartment are not yet known. By means of fluorescent immunohistochemistry in neonatal rats we therefore compared the developmental expression patterns of the vesicular glutamate transporter (VGLUT)-1 and the postsynaptic density scaffolding proteins Homer-1 and PSD-95 in the medial nucleus of the trapezoid body (MNTB). Before its formation, colocalized punctate staining of VGLUT-1 and Homer-1 or PSD-95 was observed on principal neurons, in agreement with earlier work showing that they are already innervated by fibers from the cochlear nucleus before the calyx forms. The expression of VGLUT-1 clusters within the nascent calyx of Held synapse preceded the expression of Homer-1 and PSD-95 clusters, as indicated by the presence of principal neurons with only a large contiguous cluster (LCC) of VGLUT-1 at P2-3, whereas no neurons with only an LCC for Homer-1 or PSD-95 were seen. At P3 the first principal neurons with both a pre- and a postsynaptic LCC were observed, and at P12 all principal neurons had both a pre- and a postsynaptic LCC. The relatively late appearance of Homer-1 and PSD-95 within the developing calyx of Held synapse suggests that they play a role in its stabilization and the recruitment of additional receptors to its postsynaptic density. 相似文献
8.
Mutation of the gene encoding carbonic anhydrase-related protein VIII (CAVIII) results in motor coordination deficits in mice and humans, due to loss of this protein in Purkinje cells of the cerebellum. Recent studies have indicated that the CAVIII gene, Car8, is also expressed in rod bipolar cells (RBCs), a critical glutamatergic neuron for scotopic vision. We investigated the localization of CAVIII in the mouse and macaque retina, and utilized the wdl mouse, which has a null mutation in the Car8 gene, to determine how the loss of CAVIII affects retinal signaling. CAVIII immunoreactivity was observed in RBCs, with particularly high staining intensity in the axon terminals. In addition, weaker staining was observed in a subset of cone bipolar cells and γ-aminobutyric acid (GABA)ergic amacrine cells. Light-evoked current and voltage responses of RBCs were not altered in the wdl mutant. However, light-evoked current responses from the AII-amacrine cell, a postsynaptic partner at the RBC ribbon synapse, were significantly larger, and more prolonged than in control mice. These changes could not be attributed to alterations in calcium current activation or inactivation, or to changes in the density of RBCs. Furthermore, no gross synaptic alterations were evident in the wdl mutant at the light or ultrastructural level. These data provide evidence that the CAVIII protein, which is highly conserved in vertebrates, is selectively expressed within neural circuits, and may be important for modulating retinal neurotransmission. 相似文献
9.
Torfi Sigurðsson Christopher K. Cain Valérie Doyère Joseph E. LeDoux 《The European journal of neuroscience》2010,31(2):250-262
Converging lines of evidence suggest that synaptic plasticity at auditory inputs to the lateral amygdala (LA) is critical for the formation and storage of auditory fear memories. Auditory information reaches the LA from both thalamic and cortical areas, raising the question of whether they make distinct contributions to fear memory storage. Here we address this by comparing the induction of long‐term potentation (LTP) at the two inputs in vivo in anesthetized rats. We first show, using field potential measurements, that different patterns and frequencies of high‐frequency stimulation (HFS) consistently elicit stronger LTP at cortical inputs than at thalamic inputs. Field potential responses elicited during HFS of thalamic inputs were also smaller than responses during HFS of cortical inputs, suggesting less effective postsynaptic depolarization. Pronounced differences in the short‐term plasticity profiles of the two inputs were also observed: whereas cortical inputs displayed paired‐pulse facilitation, thalamic inputs displayed paired‐pulse depression. These differences in short‐ and long‐term plasticity were not due to stronger inhibition at thalamic inputs: although removal of inhibition enhanced responses to HFS, it did not enhance thalamic LTP and left paired‐pulse depression unaffected. These results highlight the divergent nature of short‐ and long‐term plasticity at thalamic and cortical sensory inputs to the LA, pointing to their different roles in the fear learning system. 相似文献
10.
Piscopo S Moccia F Di Cristo C Caputi L Di Cosmo A Brown ER 《The European journal of neuroscience》2007,26(8):2196-2203
Synaptic transmission was examined in the plexiform zone of Octopus vulgaris optic lobes using field-potential recording from optic lobe slices. Stimulation of the optic nerve produced pre- and postsynaptic field potentials. Transmission was abolished in calcium-free seawater, L- glutamate or the AMPA/Kainate receptor blocker CNQX (EC(50), 40 microm), leaving an intact presynaptic field potential. ACh markedly reduced or blocked and d-tubocurarine augmented both pre- and postsynaptic field potentials, while alpha-bungarotoxin and atropine were without effect. Paired-pulse stimulation showed short-term depression of pre- and postsynaptic components with a half-time of recovery of approximately 500 ms. The depression was partially relieved in the presence of d-tubocurarine (half-time of recovery, 350 ms). No long-term changes in synaptic strength were induced by repetitive stimulation. A polyclonal antibody raised against a squid glutamate receptor produced positive staining in the third radial layer of the plexiform zone. No positive staining was observed in the other layers. Taking into account previous morphological data and our results, we propose that the excitatory terminations of the photoreceptors are in the innermost layer of the plexiform zone where the transmitter is likely to be glutamate and postsynaptic receptors are AMPA/kainate-like. Thus, the function of the terminal bags is to provide a location for a presynaptic cholinergic inhibitory shunt. The results imply that this arrangement provides a temporal filter for visual processing and enhances the perception of moving vs. stationary objects. 相似文献
11.
Zoltán Rusznák Balázs Pál Áron Kőszeghy Yuhong Fu Géza Szücs George Paxinos 《The European journal of neuroscience》2013,37(6):876-890
Giant cells of the cochlear nucleus are thought to integrate multimodal sensory inputs and participate in monaural sound source localization. Our aim was to explore the significance of a hyperpolarization‐activated current in determining the activity of giant neurones in slices prepared from 10 to 14‐day‐old rats. When subjected to hyperpolarizing stimuli, giant cells produced a 4‐(N‐ethyl‐N‐phenylamino)‐1,2‐dimethyl‐6‐(methylamino) pyridinium chloride (ZD7288)‐sensitive inward current with a reversal potential and half‐activation voltage of –36 and –88 mV, respectively. Consequently, the current was identified as the hyperpolarization‐activated non‐specific cationic current (Ih). At the resting membrane potential, 3.5% of the maximum Ih conductance was available. Immunohistochemistry experiments suggested that hyperpolarization‐activated, cyclic nucleotide‐gated, cation non‐selective (HCN)1, HCN2, and HCN4 subunits contribute to the assembly of the functional channels. Inhibition of Ih hyperpolarized the membrane by 6 mV and impeded spontaneous firing. The frequencies of spontaneous inhibitory and excitatory postsynaptic currents reaching the giant cell bodies were reduced but no significant change was observed when evoked postsynaptic currents were recorded. Giant cells are affected by biphasic postsynaptic currents consisting of an excitatory and a subsequent inhibitory component. Inhibition of Ih reduced the frequency of these biphasic events by 65% and increased the decay time constants of the inhibitory component. We conclude that Ih adjusts the resting membrane potential, contributes to spontaneous action potential firing, and may participate in the dendritic integration of the synaptic inputs of the giant neurones. Because its amplitude was higher in young than in adult rats, Ih of the giant cells may be especially important during the postnatal maturation of the auditory system. 相似文献
12.
Andreas Lundt Julien Sos Robin Seidel Christina Henseler Ralf Müller Varun Raj Ginde Muhammad Imran Arshaad Dan Ehninger Jürgen Hescheler Agapios Sachinidis Karl Broich Carola Wormuth Anna Papazoglou Marco Weiergrber 《The European journal of neuroscience》2020,51(7):1583-1604
Voltage‐gated Ca2+ channels (VGCCs) are considered to play a key role in auditory perception and information processing within the murine inner ear and brainstem. In the past, Cav1.3 L‐type VGCCs gathered most attention as their ablation causes congenital deafness. However, isolated patch‐clamp investigation and localization studies repetitively suggested that Cav2.3 R‐type VGCCs are also expressed in the cochlea and further components of the ascending auditory tract, pointing to a potential functional role of Cav2.3 in hearing physiology. Thus, we performed auditory profiling of Cav2.3+/+ controls, heterozygous Cav2.3+/? mice and Cav2.3 null mutants (Cav2.3?/?) using brainstem‐evoked response audiometry. Interestingly, click‐evoked auditory brainstem responses (ABRs) revealed increased hearing thresholds in Cav2.3+/? mice from both genders, whereas no alterations were observed in Cav2.3?/? mice. Similar observations were made for tone burst‐related ABRs in both genders. However, Cav2.3 ablation seemed to prevent mutant mice from total hearing loss particularly in the higher frequency range (36–42 kHz). Amplitude growth function analysis revealed, i.a., significant reduction in ABR wave WI and WIII amplitude in mutant animals. In addition, alterations in WI‐WIV interwave interval were observed in female Cav2.3+/? mice whereas absolute latencies remained unchanged. In summary, our results demonstrate that Cav2.3 VGCCs are mandatory for physiological auditory information processing in the ascending auditory tract. 相似文献
13.
The properties of pre- and postsynaptic GABAB receptors were investigated with intracellular recordings from rat neocortical neurons in vitro. An antagonist of the GABAB receptor (CGP 35348) and ions or drugs interfering with GABAB receptor-mediated K+ conductance (Ba2+, QX 314) were employed to delineate possible differences. CGP 35348 reduced the conductance of the late inhibitory postsynaptic potential (IPSPB) in a dose-dependent manner. Neither the early GABAA receptor-mediated inhibitory postsynaptic potential (IPSPA), nor resting membrane potential or direct excitability, were consistently affected by CGP 35348. Bath application of 100 μmol/l Ba2+ decreased IPSPB conductance to about 40% and increased IPSPA conductance to 130% of control. The depression of a second IPSP by a pair of stimuli (paired pulse depression, or PPD) was used as an index for presynaptic GABAB receptor activation. Neither CGP 35348 nor Ba2+ exerted significant effects on the PPD at intervals of 400 msec. The dependence of PPD on the latency of the interval of the stimulus pair was investigated after intracellular application of QX 314 had virtually abolished the IPSPB. Decreasing the stimulus interval from 500 msec to 100 msec revealed a stronger depression of the second IPSPA. Application of CGP 35348 alleviated PPD for stimulus intervals below 300 msec. The data indicate a distinct pharmacological difference between pre- and postsynaptic GABAB receptors. Moreover, we suggest that two temporally distinct presynaptic GABAB receptor effects contribute to PPD: a short-lasting effect, sensitive to CGP 35348, and a long-lasting effect, insensitive to CGP 35348. The latter is insensitive to Ba2+, implying that this component is not associated with a K− conductance mechanism. Synapse 25:62–72, 1997. © 1997 Wiley-Liss, Inc. 相似文献
14.
Daisuke Uta Hidemasa Furue Anthony E. Pickering Md Harunor Rashid Hiroko Mizuguchi‐Takase Toshihiko Katafuchi Keiji Imoto Megumu Yoshimura 《The European journal of neuroscience》2010,31(11):1960-1973
The TRPA1 channel has been proposed to be a molecular transducer of cold and inflammatory nociceptive signals. It is expressed on a subset of small primary afferent neurons both in the peripheral terminals, where it serves as a sensor, and on the central nerve endings in the dorsal horn. The substantia gelatinosa (SG) of the spinal cord is a key site for integration of noxious inputs. The SG neurons are morphologically and functionally heterogeneous and the precise synaptic circuits of the SG are poorly understood. We examined how activation of TRPA1 channels affects synaptic transmission onto SG neurons using whole‐cell patch‐clamp recordings and morphological analyses in adult rat spinal cord slices. Cinnamaldehyde (TRPA1 agonist) elicited a barrage of excitatory postsynaptic currents (EPSCs) in a subset of the SG neurons that responded to allyl isothiocyanate (less specific TRPA1 agonist) and capsaicin (TRPV1 agonist). Cinnamaldehyde evoked EPSCs in vertical and radial but not islet or central SG cells. Notably, cinnamaldehyde produced no change in inhibitory postsynaptic currents and nor did it produce direct postsynaptic effects. In the presence of tetrodotoxin, cinnamaldehyde increased the frequency but not amplitude of miniature EPSCs. Intriguingly, cinnamaldehyde had a selective inhibitory action on monosynaptic C‐ (but not Aδ‐) fiber‐evoked EPSCs. These results indicate that activation of spinal TRPA1 presynaptically facilitates miniature excitatory synaptic transmission from primary afferents onto vertical and radial cells to initiate action potentials. The presence of TRPA1 channels on the central terminals raises the possibility of bidirectional modulatory action in morphologically identified subclasses of SG neurons. 相似文献
15.
Kazuyuki Yamada Masahiro Fukaya Hidemi Shimizu Kenji Sakimura Masahiko Watanabe 《The European journal of neuroscience》2001,13(11):2025-2036
Cerebellar N-methyl-D-aspartate (NMDA) receptors are concentrated in the granular layer and are involved in motor coordination and the induction of long-term potentiation at mossy fibre-granule cell synapses. In the present study, we used immunohistochemistry to examine the distribution of NMDA receptor subunits in the adult mouse cerebellum. We found that appropriate pepsin pretreatment of sections greatly enhanced the sensitivity and specificity of immunohistochemical detection. As a result, intense immunolabelling for GluRepsilon1 (NR2A), GluRepsilon3 (NR2C), and GluRzeta1 (NR1) all appeared in synaptic glomeruli of the granular layer. Double immunofluorescence showed that these subunits were colocalized in individual synaptic glomeruli. Within the glomerulus, NMDA receptor subunits were located between centrally-located huge mossy fibre terminals and peripherally-located tiny Golgi axon terminals. By immunoelectron microscopy, all three subunits were detected at the postsynaptic junction in granule cell dendrites, forming synapses with mossy fibre terminals. Consistent with the known functional localization, GluRepsilon1, GluRepsilon3, and GluRzeta1 are, thus, anatomically concentrated at the mossy fibre-granule cell synapse. By contrast, immunohistochemical signals were very low in Purkinje cell somata and dendrites in the molecular layer. The lack of GluRzeta1 immunolabelling in Purkinje cells was unexpected because the cells express GluRzeta1 mRNA at high levels and high levels of GluRzeta1 protein in the molecular layer were revealed by immunoblot. As Purkinje cells are exceptionally lacking GluRepsilon expression, the discrepant result may provide in vivo evidence suggesting the importance of accompanying GluRepsilon subunits in synaptic localization of GluRzeta1. 相似文献
16.
The physiological effects of α1‐adrenoceptors (α1‐ARs) have been examined in many brain regions. However, little is known about the mechanism of modulation on synaptic transmission by α1‐ARs in the medial prefrontal cortex (mPFC). The present study investigated how α1‐AR activation regulates glutamatergic synaptic transmission in layer V/VI pyramidal cells of the rat mPFC. We found that the α1‐AR agonist phenylephrine (Phe) induced a significant enhancement of the amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs). The facilitation effect of Phe on the frequency of mEPSCs involved a presynaptic protein kinase C‐dependent pathway. Phe produced a significant enhancement on the amplitude of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPA‐R)‐ and N‐methyl‐d ‐aspartic acid receptor (NMDA‐R)‐mediated evoked excitatory postsynaptic currents (eEPSCs). Phe enhanced inward currents evoked by puff application of glutamate or NMDA. The Phe‐induced facilitation of AMPA‐R‐ and NMDA‐R‐mediated eEPSCs required, in part, postsynaptic Gq, phospholipase C and PKC. These findings suggest that α1‐AR activation facilitates excitatory synaptic transmission in mPFC pyramidal cells via both pre‐ and post‐synaptic PKC‐dependent mechanisms. 相似文献
17.
In the rat superior cervical ganglion, a form of long term potentiation (LTP) can be elicited by a brief high frequency stimuli applied to the preganglionic nerve. Cumulative evidence shows that a transient increase in cytoplasmic Ca2+ concentration is essential for the generation of the ganglionic LTP. Calcium influx and calcium release from intracellular calcium stores contribute to LTP. However, the differential role of presynaptic and postsynaptic calcium signaling has not been established. Herein, by using heparin, a membrane‐impermeant inositol trisphosphate receptor (IP3R) blocker, we explored the contribution of presynaptic and postsynaptic IP3‐sensitive calcium stores to the ganglionic LTP. The LTP was produced by a conditioning train of 40 Hz for 3 s. We analyzed the effects of heparin on the posttetanic potentiation: PTP magnitude and PTP time constant, and on two parameters that describe the LTP: LTP decay time (elapsed time required by the potentiated response to fall to 20% above the basal value) and LTP extent (the integral of the potentiated response). Heparin (100 and 200 μg/ml) was loaded in the preganglionic, the postganglionic, or in both nerves. We found that in all tested conditions heparin significantly decreased LTP but practically did not affect PTP. The preganglionic and postganglionic inhibitory effects of heparin were not additive. De‐N‐sulfated heparin, an ineffective IP3R blocker, had no effect on LTP, but abolished the heparin blocking effect. Data suggest that presynaptic and postsynaptic IP3‐dependent intracellular calcium release equally contribute to ganglionic LTP, supporting our proposal of a trans‐synaptic mechanism for LTP. Synapse, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
18.
Antagonism of D1/D5 receptors prevents long‐term depression (LTD) and learning‐facilitated LTD at the perforant path–dentate gyrus synapse in freely behaving rats
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Hippocampal synaptic plasticity, in the form of long‐term potentiation (LTP) and long‐term depression (LTD), enables spatial memory formation, whereby LTP and LTD are likely to contribute different elements to the resulting spatial representation. Dopamine, released from the ventral tegmental area particularly under conditions of reward, acts on the hippocampus, and may specifically influence the encoding of information into long‐term memory. The dentate gyrus (DG), as the “gateway” to the hippocampus is likely to play an important role in this process. D1/D5 dopamine receptors are importantly involved in the regulation of synaptic plasticity thresholds in the CA1 region of the hippocampus and determine the direction of change in synaptic strength that occurs during novel spatial learning. Here, we explored whether D1/D5‐receptors influence LTD that is induced in the DG following patterned afferent stimulation of the perforant path of freely behaving adult rats, or influence LTD that occurs in association with spatial learning. We found that LTD that is induced by afferent stimulation, and LTD that is facilitated by learning about novel landmark configurations, were both prevented by D1/D5‐receptor antagonism, whereas agonist activation of the D1/D5‐receptor had no effect on basal tonus or short‐term depression. Other studies have reported that in the DG, D1/D5‐receptor agonism or antagonism do not affect LTP, but agonism prevents depotentiation. These findings suggest that the dopaminergic system, acting via D1/D5‐receptors, influences information gating by the DG and modulates the direction of change in synaptic strength that underlies information storage in this hippocampal substructure. Information encoded by robust forms of LTD is especially dependent on D1/D5‐receptor activation. Thus, dopamine acting on D1/D5‐receptors is likely to support specific experience‐dependent encoding, and may influence the content of hippocampal representations of experience. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc. 相似文献
19.
Zoltán Somogyvári Dorottya Cserpán István Ulbert Péter Érdi 《The European journal of neuroscience》2012,36(10):3299-3313
Traditional current source density (tCSD) calculation method calculates neural current source distribution of extracellular (EC) potential patterns, thus providing important neurophysiological information. While the tCSD method is based on physical principles, it adopts some assumptions, which can not hold for single‐cell activity. Consequently, tCSD method gives false results for single‐cell activity. A new, spike CSD (sCSD) method has been developed, specifically designed to reveal CSD distribution of single cells during action potential generation. This method is based on the inverse solution of the Poisson‐equation. The efficiency of the method is tested and demonstrated with simulations, and showed, that the sCSD method reconstructed the original CSD more precisely than the tCSD. The sCSD method is applied to EC spatial potential patterns of spikes, measured in cat primary auditory cortex with a 16‐channel chronically implanted linear probe in vivo. Using our method, the cell–electrode distances were estimated and the spatio‐temporal CSD distributions were reconstructed. The results suggested, that the new method is potentially useful in determining fine details of the spatio‐temporal dynamics of spikes. 相似文献