Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Synaptic Transmission”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed2002

Electrophysiological analysis of synaptic transmission in central neurons of Drosophila larvae.

We report functional neuronal and synaptic transmission properties in Drosophila CNS neurons. Whole cell current- and voltage-clamp recordings were made from dorsally positioned neurons in the larval ventral nerve cord. Comparison of neuronal Green Fluorescent Protein markers and intracellular dye labeling revealed that recorded cells consisted primarily of identified motor neurons. Neurons had resting potentials of -50 to -60 mV and fired repetitive action potentials (APs) in response to depolarizing current injection. Acetylcholine application elicited large excitatory responses and AP bursts that were reversibly blocked by the nicotinic receptor antagonist D-tubocurarine (dtC). GABA and glutamate application elicited similar inhibitory responses that reversed near normal resting potential and were reversibly blocked by the chloride channel blocker picrotoxin. Multiple types of endogenous synaptically driven activity were present in most neurons, including fast spontaneous synaptic events resembling unitary excitatory postsynaptic currents (EPSCs) and sustained excitatory currents and potentials. Sustained forms of endogenous activity ranged in amplitude from smaller subthreshold "intermediate" sustained events to large "rhythmic" events that supported bursts of APs. Electrical stimulation of peripheral nerves or focal stimulation of the neuropil evoked sustained responses and fast EPSCs similar to endogenous events. Endogenous activity and evoked responses required external Ca(2+) and were reversibly blocked by dtC application, indicating that cholinergic synaptic transmission directly underlies observed activity. Synaptic current amplitude and frequency were reduced in shibire conditional dynamin mutants and increased in dunce cAMP phosphodiesterase mutants. These results complement and advance those of recent functional studies in Drosophila embryonic neurons and demonstrate the feasibility of in-depth synaptic transmission and plasticity studies in the Drosophila CNS.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

Examination of estradiol effects on the rapid estradiol mediated increase in hippocampal synaptic transmission in estrogen receptor alpha knockout mice.

Hippocampal slices from rats exhibit a rapid increase in basal synaptic transmission following 17 beta-estradiol (E(2)) application. In the current study we examined the role of the classic genomic receptor, estrogen receptor alpha (ER alpha), in mediating E(2) effects on synaptic transmission. E(2) (100 pM) increased the extracellular synaptic response in hippocampal slices from gonadectomized male and female mice lacking a functional ER alpha knockout (ER alpha KO) and wild-type (WT) littermates. No sexually dimorphic differences were observed, however, the increase in the field potential was more pronounced in WT mice. ER antagonists did not block E(2) mediated growth of the synaptic response in ER alpha KO mice. The results suggest that the rapid effect of E(2) on synaptic transmission is not mediated by ER alpha, however, ER alpha appears to modulate non-genomic influences on synaptic transmission.

Animals↗
PubMed1999

Calcium channels involved in synaptic transmission from reticulospinal axons in lamprey.

The pharmacology of calcium channels involved in glutamatergic synaptic transmission from reticulospinal axons in the lamprey spinal cord was analyzed with specific agonists and antagonists of different high-voltage activated calcium channels. The N-type calcium channel blocker omega-conotoxin GVIA (omega-CgTx) induced a large decrease of the amplitude of reticulospinal-evoked excitatory postsynaptic potentials (EPSPs). The P/Q-type calcium channel blocker omega-agatoxin IVA (omega-Aga) also reduced the amplitude of the reticulospinal EPSPs, but to a lesser extent than omega-CgTx. The dihydropyridine agonist Bay K and antagonist nimodipine had no effect on the amplitude of the reticulospinal EPSP. Combined application of omega-CgTx and omega-Aga strongly decreased the amplitude the EPSPs but was never able to completely block them, indicating that calcium channels insensitive to these toxins (R-type) are also involved in synaptic transmission from reticulospinal axons. We have previously shown that the group III metabotropic glutamate receptor agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4) mediates presynaptic inhibition at the reticulospinal synapse. To test if this presynaptic effect is mediated through inhibition of calcium influx, the effect of L-AP4 on reticulospinal transmission was tested before and after blockade of N-type channels, which contribute predominantly to transmitter release at this synapse. Blocking the N-type channels with omega-CgTx did not prevent inhibition of reticulospinal synaptic transmission by L-AP4. In addition, L-AP4 had no affect on the calcium current recorded in the somata of reticulospinal neurons or on the calcium component of action potentials in reticulospinal axons. These results show that synaptic transmission from reticulospinal axons in the lamprey is mediated by calcium influx through N-, P/Q- and R-type channels, with N-type channels playing the major role. Furthermore, presynaptic inhibition of reticulospinal transmission by L-AP4 appears not to be mediated through inhibition of presynaptic calcium channels.

Animals↗
PubMed2003

Modulation of spike-mediated synaptic transmission by presynaptic background Ca2+ in leech heart interneurons.

At the core of the rhythmically active leech heartbeat central pattern generator are pairs of mutually inhibitory interneurons. Synaptic transmission between these interneurons consists of spike-mediated and graded components, both of which wax and wane on a cycle-by-cycle basis. Low-threshold Ca2+ currents gate the graded component. Ca imaging experiments indicate that these low-threshold currents are widespread in the neurons and that they contribute to neuron-wide changes in internal background Ca2+ concentration (Ivanov and Calabrese, 2000). During normal rhythmic activity, background Ca2+ concentration oscillates, and thus graded synaptic transmission waxes and wanes as the neurons move from the depolarized to the inhibited phases of their activity. Here we show that in addition to gating graded transmitter release, the background Ca2+ concentration changes evoked by low-threshold Ca2+ currents modulate spike-mediated synaptic transmission. We develop stimulation paradigms to simulate the changes in baseline membrane potential that accompany rhythmic bursting. Using Ca imaging and electrophysiological measurements, we show that the strength of spike-mediated synaptic transmission follows the changes in background Ca2+ concentration that these baseline potential changes evoke and that it does not depend on previous spike activity. Moreover, we show using internal EGTA and photo-release of caged Ca2+ and caged Ca2+ chelator that changes in internal Ca2+ concentration modulate spike-mediated synaptic transmission. Thus activity-dependent changes in background Ca2+, which have been implicated in homeostatic regulation of intrinsic membrane currents and synaptic strength, may also regulate synaptic transmission in an immediate way to modulate synaptic strength cycle by cycle in rhythmically active networks.

Action Potentials↗
PubMed2003

Learning in spiking neural networks by reinforcement of stochastic synaptic transmission.

It is well-known that chemical synaptic transmission is an unreliable process, but the function of such unreliability remains unclear. Here I consider the hypothesis that the randomness of synaptic transmission is harnessed by the brain for learning, in analogy to the way that genetic mutation is utilized by Darwinian evolution. This is possible if synapses are "hedonistic," responding to a global reward signal by increasing their probabilities of vesicle release or failure, depending on which action immediately preceded reward. Hedonistic synapses learn by computing a stochastic approximation to the gradient of the average reward. They are compatible with synaptic dynamics such as short-term facilitation and depression and with the intricacies of dendritic integration and action potential generation. A network of hedonistic synapses can be trained to perform a desired computation by administering reward appropriately, as illustrated here through numerical simulations of integrate-and-fire model neurons.

Action Potentials↗
PubMed2003

Co-stimulation of mGluR5 and N-methyl-D-aspartate receptors is required for potentiation of excitatory synaptic transmission in hippocampal neurons.

In the central nervous system, excitatory synaptic transmission is mediated by the neurotransmitter glutamate and its receptors. Interestingly, stimulation of group I metabotropic glutamate receptors (mGluRs) can either enhance or depress synaptic transmission at CA1 hippocampal synapses. Here we report that co-activation of mGluR5, a member of the group I mGluR family, and N-methyl-d-aspartate receptors (NMDARs) potentiates NMDAR currents and induces a long lasting enhancement of excitatory synaptic transmission in primary cultured hippocampal neurons. Unexpectedly, activation of mGluR5 alone fails to enhance evoked NMDAR currents and synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) AMPAR currents. The observed potentiation requires an mGluR5-induced, inositol 1,4,5-trisphosphate receptor-mediated mobilization of intracellular Ca2+, which acts in concert with a protein kinase C, calcium-activated tyrosine kinase cascade to induce a long lasting enhancement of NMDAR and AMPAR currents.

Alkaloids↗
PubMed1996

Homeostasis of synaptic transmission in Drosophila with genetically altered nerve terminal morphology.

We present a new test of the hypothesis that synaptic strength is directly related to nerve terminal morphology through analysis of synaptic transmission at Drosophila neuromuscular junctions with a genetically reduced number of nerve terminal varicosities. Synaptic transmission would decrease in target cells with fewer varicosities if there is a relationship between the number of varicosities and the strength of synaptic transmission. Animals that have an extreme hypomorphic allele of the gene for the cell adhesion molecule Fasciclin II possess fewer synapse-bearing nerve terminal varicosities; nevertheless, synaptic strength is maintained at a normal level for the muscle cell as a whole. Fewer failures of neurotransmitter release and larger excitatory junction potentials from individual varicosities, as well as more frequent spontaneous release and larger quantal units, provide evidence for enhancement of transmitter release from varicosities in the mutant. Ultrastructural analysis reveals that mutant nerve terminals have bigger synapses with more active zones per synapse, indicating that synaptic enlargement and an accompanying increase in synaptic complexity provide for more transmitter release at mutant varicosities. These results show that morphological parameters of transmitting nerve terminals can be adjusted to functionally compensate for genetic perturbations, thereby maintaining optimal synaptic transmission.

Animals↗
PubMed2006

Monitoring synaptic transmission in primary neuronal cultures using local extracellular stimulation.

Various techniques have been applied for the functional analysis of synaptic transmission in cultured neurons. Here, we describe a method of studying synaptic transmission in neurons cultured at high-density from different brain regions such as the cortex, striatum and spinal cord. We use postsynaptic whole-cell recordings to monitor synaptic currents triggered by presynaptic action potentials that are induced by brief stimulations with a nearby extracellular bipolar electrode. Pharmacologically isolated excitatory or inhibitory postsynaptic currents can be reliably induced, with amplitudes, synaptic charge transfers, and short-term plasticity properties that are reproducible from culture to culture. We show that the size and kinetics of pharmacologically isolated inhibitory postsynaptic currents triggered by single action potentials or stimulus trains depend on the Ca2+ concentration, temperature and stimulation frequency. This method can be applied to study synaptic transmission in wildtype neurons infected with lentiviruses encoding various components of presynaptic release machinery, or in neurons from genetically modified mice, for example neurons carrying floxed genes in which gene expression can be acutely ablated by expression of Cre recombinase. The preparation described in this paper should be useful for analysis of synaptic transmission in inter-neuronal synapses formed by different types of neurons.

Animals↗
PubMed1988

Long-term potentiation of synaptic transmission in kitten visual cortex.

1. Potentiation of synaptic transmission in visual cortex (areas 17 and 18) of kittens was investigated by extracellular recording of field potentials (FPs) and cortical units in cortical slices and whole-animal preparations. Responses to test stimulation (0.05 Hz) of the white matter (WM), lateral geniculate nucleus (LGN), and optic chiasm (OC) were documented before and after conditioning stimulation (2 Hz for 1 h). 2. In slice preparations of area 17, the FPs were always depressed during conditioning stimulation and were usually potentiated immediately after conditioning stimulation. Long-term potentiation (LTP) of FPs developed rapidly during the initial 1-2 h and continued to increase slowly for several hours after conditioning. 3. LTP of FPs was age dependent: LTP occurred most frequently (43/53) at the ages of 21-34 days, less frequently (4/7 and 5/11) at 14-20 and 35-41 days, and never (0/5 and 0/5) at 7-13 and 42-49 days. LTP age relationship determined as a ratio of the amplitudes of FPs after conditioning to that before conditioning was greater at 21-34 days (mean potentiation, 2.4 +/- 0.6) than at 14-20 or 35-41 days (1.7 +/- 0.5). 4. LTP was also documented by the shortening in latencies of orthodromic responses of cortical units sampled from 10 pairs of conditioned and unconditioned control slices. Unit responses were classified into mono- and polysynaptic groups according to the central delay, defined as the time required for their activation after the arrival of afferent impulses. The monosynaptic central delays were 0.22 ms shorter in conditioned (0.60 +/- 0.17 ms, n = 56) than in control slices (0.82 +/- 0.22 ms, n = 57); similarly, polysynaptic central delays were 0.66 ms smaller (1.70 +/- 0.43 ms, n = 51; and 2.36 +/- 0.79 ms, n = 51). Both differences were statistically significant (P less than 0.001). 5. There were laminar differences in LTP of mono- and polysynaptic transmission. LTP of monosynaptic transmission occurred throughout layers II-V (central delays shortened about 0.2 ms), whereas LTP of polysynaptic transmission was greatest in layer II (1.17 ms), moderate in layer III (0.66 ms), and slight in layer IV (0.3 ms). The time course of shortening in orthodromic latency in five polysynaptic units agreed with the time course of LTP of FP. 6. Location of synapses involved in LTP of synaptic transmission was studied by current source-density (CSD) analysis in slice preparations of area 17 during test stimulation of WM. CSD analysis demonstrated two components of current sinks (early and late), probably representing mono- and polysynaptic transmission.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2005

Deletion of presynaptic adenosine A1 receptors impairs the recovery of synaptic transmission after hypoxia.

Adenosine protects neurons during hypoxia by inhibiting excitatory synaptic transmission and preventing NMDA receptor activation. Using an adeno-associated viral (AAV) vector containing Cre recombinase, we have focally deleted adenosine A(1) receptors in specific hippocampal regions of adult mice. Recently, we found that deletion of A(1) receptors in the CA1 area blocks the postsynaptic responses to adenosine in CA1 pyramidal neurons, and deletion of A(1) receptors in CA3 neurons abolishes the presynaptic effects of adenosine on the Schaffer collateral input [J Neurosci 23 (2003) 5762]. In the current study, we used this technique to delete A(1) receptors focally from CA3 neurons to investigate whether presynaptic A(1) receptors protect synaptic transmission from hypoxia. We studied the effects of prolonged (1 h) hypoxia on the evoked field excitatory postsynaptic potentials (fEPSPs) in the CA1 region using in vitro slices. Focal deletion of the presynaptic A(1) receptors on the Schaffer collateral input slowed the depression of the fEPSPs in response to hypoxia and impaired the recovery of the fEPSPs after hypoxia. Delayed responses to hypoxia linearly correlated with impaired recovery. These findings provide direct evidence that the neuroprotective role of adenosine during hypoxia depends on the rapid inhibition of synaptic transmission by the activation of presynaptic A(1) receptors.

Adenosine A1 Receptor Antagonists↗
PubMed2002

Calcium channel structural determinants of synaptic transmission between identified invertebrate neurons.

We report here that unlike what was suggested for many vertebrate neurons, synaptic transmission in Lymnaea stagnalis occurs independent of a physical interaction between presynaptic calcium channels and a functional complement of SNARE proteins. Instead, synaptic transmission in Lymnaea requires the expression of a C-terminal splice variant of the Lymnaea homolog to mammalian N- and P/Q-type calcium channels. We show that the alternately spliced region physically interacts with the scaffolding proteins Mint1 and CASK, and that synaptic transmission is abolished following RNA interference knockdown of CASK or after the injection of peptide sequences designed to disrupt the calcium channel-Mint1 interactions. Our data suggest that Mint1 and CASK may serve to localize the non-L-type channels at the active zone and that synaptic transmission in invertebrate neurons utilizes a mechanism for optimizing calcium entry, which occurs independently of a physical association between calcium channels and SNARE proteins.

Animals↗
PubMed1999

Timing of synaptic transmission.

Many behaviors require rapid and precisely timed synaptic transmission. These include the determination of a sound's direction by detecting small interaural time differences and visual processing, which relies on synchronous activation of large populations of neurons. In addition, throughout the brain, concerted firing is required by Hebbian learning mechanisms, and local circuits are recruited rapidly by fast synaptic transmission. To achieve speed and precision, synapses must optimize the many steps between the firing of a presynaptic cell and the response of its postsynaptic targets. Until recently, the behavior of mammalian synapses at physiological temperatures was primarily extrapolated from studies at room temperature or from the properties of invertebrate synapses. Recent studies have revealed some of the specializations that make synapses fast and precise in the mammalian central nervous system at physiological temperatures.

Action Potentials↗
PubMed1991

FMRFamide modulation of secretory machinery underlying presynaptic inhibition of synaptic transmission requires a pertussis toxin-sensitive G-protein.

The neuropeptide FMRFamide modulates synaptic transmission between identified neurons of the pond snail Helisoma trivolvis. FMRFamide causes a presynaptic inhibition of transmitter release by actions on ion channels and secretory machinery (Man-Son-Hing et al., 1989). The actions of FMRFamide on secretory machinery were studied using giant synapses that form between somata in culture. Using the calcium cage DM-nitrophen, synchronized, calcium-clamped release of neurotransmitter was promoted by UV photolysis. A series of UV flashes (15 msec duration) repeatedly promoted the transient synchronized release of neurotransmitter. Addition of FMRFamide reduced the magnitude of these flash-evoked inhibitory postsynaptic currents. Under conditions of synchronized transmitter release, FMRFamide modulates the secretory responsiveness to internal calcium. The release of neurotransmitter at somasoma synapses was determined to be quantal in nature. To test for the involvement of G-proteins in mediating the effects of FMRFamide on secretory machinery, the modulation of the frequency of miniature inhibitory postsynaptic currents (MIPSCs) was examined. Addition of FMRFamide reduced the frequency of MIPSCs without affecting intracellular free calcium measured with fura-2. Injection of a nonhydrolyzable analog of GTP, GTP gamma S, mimicked the effect of FMRFamide and reduced MIPSC frequency. Preinjection of the presynaptic soma with the A-protomer of pertussis toxin (PTX) prevented FMRFamide from reducing MIPSC frequency. Thus, a PTX-sensitive G-protein mediates the action of FMRFamide on secretory machinery. Similarly, preinjection of the presynaptic soma with PTX prevented FMRFamide from reducing the magnitude of action potential-evoked IPSC. Dose-response curves for the actions of FMRFamide on secretory machinery and calcium current were constructed and demonstrated that secretory machinery can be modulated at concentrations of FMRFamide (less than or equal to 10(-7) M) that do not affect calcium current magnitude. At a concentration of 10(-7) M FMRFamide, action potential-evoked synaptic transmission was reduced. Thus, synaptic transmission can be regulated by the modulation of secretory machinery, without a requirement for the modulation of ion channels.

Animals↗
PubMed1999

Excitatory but not inhibitory synaptic transmission is reduced in lethargic (Cacnb4(lh)) and tottering (Cacna1atg) mouse thalami.

Excitatory but not inhibitory synaptic transmission is reduced in lethargic (Cacnb4(lh)) and tottering (Cacna1atg) mouse thalami. Recent studies of the homozygous tottering (Cacna1atg) and lethargic mouse (Cacnb4(lh)) models of absence seizures have identified mutations in the genes encoding the alpha1A and beta4 subunits, respectively, of voltage-gated Ca2+ channels (VGCCs). beta subunits normally regulate Ca2+ currents via a direct interaction with alpha1 (pore-forming) subunits of VGCCs, and VGCCs are known to play a significant role in controlling the release of transmitter from presynaptic nerve terminals in the CNS. Because the gene mutation in Cacnb4(lh) homozygotes results in loss of the beta4 subunit's binding site for alpha1 subunits, we hypothesized that synaptic transmission would be altered in the CNS of Cacnb4(lh) homozygotes. We tested this hypothesis by using whole cell recordings of single cells in an in vitro slice preparation to investigate synaptic transmission in one of the critical neuronal populations that generate seizure activity in this strain, the somatosensory thalamus. The primary finding reported here is the observation of a significant decrease in glutamatergic synaptic transmission mediated by both N-methyl-D-aspartate (NMDA) and non-NMDA receptors in somatosensory thalamic neurons of Cacnb4(lh) homozygotes compared with matched, nonepileptic mice. In contrast, there was no significant decrease in GABAergic transmission in Cacnb4(lh) homozygotes nor was there any difference in effects mediated by presynaptic GABAB receptors. We found a similar decrease in glutamatergic but not GABAergic responses in Cacna1atg homozygotes, suggesting that the independent mutations in the two strains each affected P/Q channel function by causing defective neurotransmitter release specific to glutamatergic synapses in the somatosensory thalamus. This may be an important factor underlying the generation of seizures in these models.

Animals↗
PubMed1998

Antisense oligonucleotides to the GluR2 AMPA receptor subunit modify excitatory synaptic transmission in vivo.

In the brain, fast wxcitatory synaptic transmission is mostly mediated by the alpha-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) subtype of the glutamate receptors. Molecular cloning has revealed that four subunits, GluR1, GluR2, GluR3, and GluR4 form heteromeric receptors with high affinity for AMPA. Because antagonists and agonists do not discriminate between individual AMPA receptor subunits, we decided to use antisense oligonucleotides to block the expression of the GluR2 subunit within the receptor complex in adult animals. In the present study, we exploited several advantages afforded by the guinea pig cochlea to determine whether an antisense oligonucleotide directed to the mRNA of the GluR2 subunit could modify primary auditory neurotransmission. While a random probe with the same base composition had no effect, a GluR2 antisense oligonucleotide, continuously delivered into the cochlea, transiently reduced the compound action potential and diminished spontaneous activity of single auditory nerve fibers. Although antisense oligonucleotides penetrated a variety of cells, their effect could be physiologically localized to a single site of GluR2 antisense probe action, the primary auditory neuron. Subunit specificity of this effect was confirmed by a significant reduction in GluR2/3, but not GluR4 immunoreactivity in primary auditory neurons. Besides being the first demonstration that transient knockout of GluR2 subunit in adult animal modifies excitatory synaptic transmission in vivo, these results support the use of the antisense strategy as a powerful tool for blocking expression of any gene in the cochlea.

Acoustic Stimulation↗
PubMed2003

Miniature synaptic transmission and BDNF modulate dendritic spine growth and form in rat CA1 neurones.

The refinement and plasticity of neuronal connections require synaptic activity and neurotrophin signalling; their specific contributions and interplay are, however, poorly understood. We show here that brain-derived neurotrophic factor (BDNF) increased spine density in apical dendrites of CA1 pyramidal neurones in organotypic slice cultures prepared from postnatal rat hippocampal slices. This effect was observed also in the absence of action potentials, and even when miniature synaptic transmission was inhibited with botulinum neurotoxin C (BoNT/C). There were, however, marked differences in the morphology of individual spines induced by BDNF across these different levels of spontaneous ongoing synaptic activity. During both normal synaptic transmission, and when action potentials were blocked with TTX, BDNF increased the proportion of stubby, type-I spines. However, when SNARE-dependent vesicular release was inhibited with BoNT/C, BDNF increased the proportion of thin, type-III spines. Our results indicate that BDNF increases spine density irrespective of the levels of synaptic transmission. In addition, miniature synaptic transmission provides sufficient activity for the functional translation of BDNF-triggered spinogenesis into clearly defined morphological spine types, favouring those spines potentially responsible for coordinated Ca2+ transients thought to mediate synaptic plasticity. We propose that BDNF/TrkB signalling represents a mechanism of expression of both morphological and physiological homeostatic plasticity in the hippocampus, leading to a more efficient synaptic information transfer across widespread levels of synaptic activity.

Action Potentials↗
PubMed1988

Synthetic omega-conotoxin blocks synaptic transmission in the hippocampus in vitro.

The effects of some organic calcium channel blockers and a toxin on synaptic transmission were examined in hippocampal slices from the guinea pig. omega-Conotoxin fraction GVIA, a novel peptide that blocks N and L type voltage-sensitive calcium channels, blocked synaptic transmission from mossy fibers to CA3 neurons at very low concentration (100 nM). However, organic calcium channel blockers such as verapamil (100 microM) and nifedipine (10 microM), which block L type calcium channels, had little effect on the synaptic transmission. Phenytoin (100 microM, T type calcium channel blocker) was also ineffective to block the synaptic transmission. These results suggest that presynaptic calcium channels which cause transmitter release may be N type calcium channel.

Animals↗
PubMed1992

Pharmacological characterization of calcium currents and synaptic transmission between thalamic neurons in vitro.

We recorded from pairs of cultured, synaptically connected thalamic neurons. Evoked excitatory postsynaptic currents (EPSCs) reversed at +17 mV and were blocked reversibly by 1 mM kynurenic acid, a glutamate receptor antagonist. NMDA and non-NMDA receptors mediated excitatory post-synaptic responses, as shown by selective block of EPSC components with 50 microM (+/-)-2-amino-5-phosphonopentanoic acid and 10 microM 6,7-dinitroquinoxaline-2,3-dione, respectively. Inhibitory postsynaptic responses were evoked less frequently and were blocked by the GABAA receptor antagonist (-)-bicuculline methochloride. The pharmacological profiles of whole-cell calcium currents and evoked EPSCs were compared. With 50 microM cadmium chloride (Cd), whole-cell low voltage-activated (LVA) calcium currents were reduced in amplitude and high voltage-activated (HVA) calcium currents and excitatory synaptic transmission were completely blocked. This suggests that the residual calcium influx through LVA channels into the presynaptic terminal does not suffice to trigger transmitter release. A saturating concentration of omega-conotoxin GVIA (omega-CgTx) (2.5 microM) blocked one-third of whole-cell HVA calcium currents and evoked EPSCs. The dihydropyridine nifedipine (50 microM) reversibly reduced whole-cell HVA calcium currents in a voltage-dependent manner but not excitatory synaptic transmission. Cd and omega-CgTx did not alter amplitude distributions of miniature EPSCs, demonstrating that the inhibition of synaptic transmission was due to block of presynaptic calcium channels. We conclude that excitatory glutamatergic transmission in thalamic neurons in vitro was mediated mainly by HVA calcium currents, which were insensitive to omega-CgTx and nifedipine.

Animals↗