Interaction between inhibitory and excitatory synaptic potentials at a peripheral neurone.

1. The interaction between inhibitory and excitatory synaptic potentials in neurones lying in the submucous plexus of guinea-pig ileum has been examined. 2. It was found that during an inhibitory conductance change, electrotonic potentials were more depressed in amplitude than were excitatory synaptic potentials. 3. It is suggested that inhibitory conductance changes may have only a slight effect on the impedance seen by excitatory synaptic currents as much of the excitatory synaptic current flow is likely to be capacitive. 4. A part of the depression of excitatory synaptic potential amplitude was not associated with changes in electrical properties of neurones and it is suggested that inhibitory transmitter may reduce the release of excitatory transmitter.     

Ultrastructure of the terminals of an identified dopamine-containing neurone markedby intracellular injection of radioactive dopamine.

The terminal processes of an identified dopamine-containing neurone in the central nervous system of the water snail were located for study with the electron microscope. This was achieved by intracellular injection of 3-H-dopamine followed by light and electron microscope autoradiography. The neurone showed extensive branching in ganglia whereprevious electrophysiological work had shown the presence of postsynaptic neurones. The terminal processes in these ganglia contained dense-cored vesicles of 50-250 nm diametersimilar to those in the perikaryon. Vesicles were found in large numbers in certain lacalized regions which may be synaptic terminals. The vesicles, which appear to take updopamine, tended to be smaller in the presumed terminal regions than in the preterminals and the perikaryon. No membrane specializations associated with typical synapses were observed.     

Excitatory potentials induced by stimulation of the inhibitory axon at the crustacean neuromuscular junction.

Synaptic events in a chloride-deficient condition were studied to elucidate functional aspects of presynaptic inhibitory synapses. The extracellular junctional potentials and nerve terminal potentials were concurrently recorded from a synaptic region. Inhibitory stimulation produced repetitive spikes on the inhibitory nerve terminal and then the excitatory nerve terminal, which resulted in the extracellular excitatory junctional potentials. Excitatory stimulation did not produce repetitive spikes on the inhibitory nerve terminal, indicating one-way signal transmission in this axo-axonal synapse from inhibitory to excitatory axon. The interval required for an inhibitory stimulation to produce the first response in the postsynaptic muscle membrane ranged widely from 10 to 800 msec. When gamma-aminobutyric acid (GABA, 1 times 10-minus 4 M) was added in these experimental conditions, the muscle membrane was transiently depolarized by about 10 mV. The action of GABA mimics that of the neurotransmitter at presynaptic inhibitory synapses. The experimental observations may be well explained by the concept of synapses on synapses, i.e., presynaptic inhibition, where the neurotransmitter may be GABA and chloride ions may be playing essential roles as in the case of postsynaptic inhibition.     

Modulation of inhibitory synaptic potentials in the piriform cortex.

Modulation of inhibitory synaptic potentials in the piriform cortex. Intracellular recordings from pyramidal neurons in brain slice preparations of the piriform cortex were used to test results from a computational model about the effects of cholinergic agonists on inhibitory synaptic potentials induced by stimulation of afferent fibers in layer Ia and association/intrinsic fibers in layer Ib. A simple model of piriform cortex as an associative memory was used to analyze how suppression of inhibitory synaptic transmission influenced performance of the network. Levels of suppression of excitatory synaptic transmission were set at levels determined in previous experimental work. Levels of suppression of inhibitory synaptic transmission were then systematically varied within the model. This modeling work demonstrated that suppression of inhibitory synaptic transmission in layer Ib should be stronger than suppression of inhibitory synaptic transmission in layer Ia to keep activity levels high enough for effective storage. Experimental data showed that perfusion of the cholinergic agonist carbachol caused a significant suppression of inhibitory postsynaptic potentials (IPSPs) in the pyramidal neurons that were induced by stimulation of layer Ib, with a weaker effect on IPSPs induced by stimulation of layer Ia. As previously described, carbachol also selectively suppressed excitatory postsynaptic potentials (EPSPs) elicited by intrinsic but not afferent fiber stimulation. The decrease in amplitude of IPSPs induced by layer Ib stimulation did not appear to be directly related to the decrease in EPSP amplitude induced by layer Ib stimulation. The stimulation necessary to induce neuronal firing with layer Ia stimulation was reduced in the presence of carbachol, whereas that necessary to induce neuronal firing with layer Ib stimulation was increased, despite the depolarization of resting membrane potential. Thus physiological data on cholinergic modulation of inhibitory synaptic potentials in the piriform cortex is compatible with the functional requirements determined from computational models of piriform cortex associative memory function.     

Excitatory and inhibitory postsynaptic potentials in cat hypoglossal motoneurons during swallowing

Summary The postsynaptic potentials produced in cat genioglossus and styloglossus motoneurons (GG- and SG-Mns) during swallowing were studied. During swallowing elicited by placing water on the dorsum of the tongue, the GG-muscle discharged for 80–210 ms (mean±S. D. 123±31 ms, N=59) and was abruptly suppressed, and the SG-muscle began discharging in synchrony with the GG-muscle and discharged for 200–360 ms (mean+ S. D. 247±36 ms, N=59). The GG and the SG-Mns were identified if unitary muscle activity followed the induced spike of the motoneuron one-for-one. During swallowing, excitatory postsynaptic potentials (EPSPs) were evoked in the SG-Mns regardless of the respiratory drive on the SG-Mns, and inhibitory postsynaptic potential (IPSP) or EPSP-IPSP was evoked on the GG-Mns regardless of the respiratory drive on the GG-Mns. By increasing the intracellular concentration of chloride ions, the IPSP elicited in the GG-Mn during swallowing was turned into a depolarizing potential. In immobilized cats, a depolarizing potential and a depolarizing-hyperpolarizing potential sequence was evoked successively on a tongue retractor motoneuron and a tongue protruder motoneuron by repetitive electrical stimulation of the superior laryngeal nerve.     

Excitatory synaptic potentials in neurons of the deep nuclei in olivo-cerebellar slice cultures.

Excitatory postsynaptic potentials evoked in neurons of the deep cerebellar nuclei, either by electrical stimulation within the nuclei in cerebellar slice cultures or by electrical stimulation of olivary explants in olivo-cerebellar co-cultures, were investigated in the rat by means of intracellular recordings. In neurons of the deep cerebellar nuclei, stimulation of the nuclear tissue, as well as stimulation of the olivary tissue, induced a fast rising excitatory postsynaptic potential, followed by an inhibitory postsynaptic potential and a long-lasting excitation. The fast rising excitatory postsynaptic potential and the following inhibitory postsynaptic potential were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione. The remaining depolarization was abolished by D-(-)-2-amino-5-phosphonovalerate, suggesting that this potential was mediated by N-methyl-D-aspartate receptors. With only D-(-)-2-amino-5-phosphonovalerate added to the bath, the slow excitation was depressed, whereas the fast excitatory and inhibitory postsynaptic potentials were not affected. In the presence of bicuculline, the 6-cyano-7-nitroquinoxaline-2,3-dione- and the D-(-)-2-amino-5-phosphonovalerate-sensitive excitatory postsynaptic potentials elicited by stimulation of the olivary tissue had the same latency, and were both graded with stimulation strength. The time-to-peak and the duration of the D-(-)-2-amino-5-phosphonovalerate-sensitive excitatory postsynaptic potentials were considerably longer than those of the 6-cyano-7-nitroquinoxaline-2,3-dione-sensitive excitatory postsynaptic potentials.(ABSTRACT TRUNCATED AT 250 WORDS)     

Excitatory synaptic transmission in the spinal substantia gelatinosa is under an inhibitory tone of endogenous adenosine

Exogenous adenosine produces potent synaptic inhibition in spinal substantia gelatinosa (SG), a region involved in nociceptive and thermoreceptive mechanisms. To examine the possibility that endogenous adenosine tonically modulates excitatory synaptic transmission in spinal SG, whole-cell, voltage-clamp recordings were made from SG neurons in adult rat spinal cord slices. In all SG neurons sensitive to exogenous adenosine, the adenosine uptake inhibitor, NBTI, mimics adenosine's inhibitory actions on dorsal root evoked EPSCs (eEPSCs) and miniature spontaneous EPSCs (mEPSCs). These inhibitory effects were antagonized by A1 adenosine receptor antagonist, DPCPX. DPCPX also potentates eEPSCs in those SG neurons in which adenosine or adenosine A1 receptor agonists (CHA, CCPA) suppressed eEPSCs. DPCPX often increases mEPSC frequency without altering mEPSC amplitude, suggesting presynaptic action on adenosine A1 receptors. Selective A2 (DMPX) and A2a (ZM 241385) adenosine receptor antagonists had no or minimal effects upon either eEPSCs or mEPSCs. The adenosine degrading enzyme, adenosine deaminase, mimicked the effects of DPCPX on the mEPSC frequency. We conclude that the excitatory synaptic transmission in the spinal SG is under an inhibitory tone of endogenous adenosine through the activation of A1 receptors. The present results suggested that the background activity of A1 receptors in the spinal SG might be contributed to setting the physiological “noceceptive thresholds”.     

Presynaptic inhibition produced by an identified presynaptic inhibitory neuron. I. Physiological mechanisms

We have examined the synaptic conductance mechanisms underlying presynaptic inhibition in Aplysia californica in a circuit in which all the neural elements are identified cells (Fig. 1). L10 makes connections to identified follower cells (RB and left upper quadrant cells, L2-L6). These connections are presynaptically inhibited by stimulating cells of the L32 cluster (4). L32 cells produce a slow inhibitory synaptic potential on L10. This inhibitory synaptic potential is associated with an apparent increased membrane conductance in L10. Both the inhibitory postsynaptic potential (IPSP) and the conductance increase are voltage dependent; the IPSP could not be reversed by hyperpolarizing the membrane potentials to - 120 mV. The hyperpolarization of L10 induced by L32 reduces the transmitter output of L10 and thereby contributes to presynaptic inhibition. However, this hyperpolarization accounts for about 30% of the effect because presynaptic inhibition can still be observed even when the hyperpolarization of L10 by L32 is prevented by voltage clamping. When L10 is voltage clamped, stimulation of L32 produces a slow outward synaptic current associated with an apparent increased conductance. Both the synaptic current and conductance change measured under clamp are voltage dependent, and the outward current could not be reversed. This synaptic current is not mediated by an increase in C1- conductance. It is sensitive to external K+ concentration, especially at hyperpolarized membrane potentials. With L10 under voltage clamp, stimulation of L32 also reduces a slow inward current in L10. This current has time and voltage characteristics similar to those of the Ca2+ current. Presynaptic inhibition is still produced by L32 when L10 is voltage clamped, and transmitter release is elicited by depolarizing voltage-clamp pulses. This component of presynaptic inhibition, which accounts for approximately 70% of the inhibition, appears to be due to a decrease in the Ca2+ current in the presynaptic neuron.     

Interaction between neurone and microglia mediated by platelet-activating factor

BACKGROUND: Platelet-activating factor (PAF) is a potent phospholipid mediator that plays various roles in neuronal function and brain development. The production and release of PAF in the brain has also been reported under various pathological conditions. However, neither the cell types and mechanism responsible for the synthesis of PAF nor its target cells have been fully identified. RESULTS: Using primary culture cells derived from rat brain and a very sensitive assay method for PAF, we found that PAF was synthesized in neurones following stimulation with glutamic acid. PAF synthesis required activation of NMDA receptors and subsequent elevation of intracellular calcium ions. Microglia, which express functional PAF receptors to a high level, showed a marked chemotactic response to PAF. This chemotaxis is a receptor-mediated process, as microglia from PAF-receptor-deficient mice did not show such a response. The activation of a pertussis-toxin-sensitive G-protein and mitogen-activated protein kinase presumably plays a role in intracellular signalling leading to chemotaxis. CONCLUSIONS: Considering the cytoprotective and cytotoxic roles of microglia, PAF functions as a key messenger in neurone-microglial interactions.     

Excitatory and inhibitory postsynaptic potentials in alpha-motoneurons produced during fictive locomotion by stimulation of the mesencephalic locomotor region

We tested the hypothesis that stimulation of the mesencephalic locomotor region (MLR) activates polysynaptic pathways that project to lumbar spinal motoneurons and are involved in the initiation of locomotion. Fictive locomotion was produced by MLR stimulation, and intracellular records of evoked postsynaptic potentials (PSPs) in alpha-motoneurons were computer analyzed. Stimulation of sites in the MLR that were maximally effective for the initiation of locomotion produced excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) in all the motoneurons examined. The amplitudes of the PSPs increased as locomotion commenced. The EPSPs were largest during the depolarized phase of the step cycle, and in 17 of our 22 cells the EPSP was replaced by an IPSP of slightly longer latency during the hyperpolarized phase. The mean latency of the EPSPs measured from the stimulus artifact produced by stimulation of the MLR was 5.1 ms (3.0-7.0 ms). In all cases, the IPSP occurred 0.6 ms or more after the onset of the EPSP in the same cell. Later PSPs were sometimes observed as well. The effects of constant current injection on the membrane potential oscillations associated with fictive locomotion (locomotor drive potentials) were examined. The results showed that the amplitudes of the locomotor drive potentials (LDPs) could be affected by depolarizing and hyperpolarizing current injection. The data is consistent with the LDP having a predominant inhibitory component, which is more readily altered by current injection than is the excitatory component. The effect of constant current injections on the MLR-evoked PSPs was also examined, and it was observed that both EPSPs and IPSPs could be affected by the injected currents. The EPSPs increased in amplitude with constant hyperpolarizing current injection, and this fact rules out the possibility that the EPSP is actually a reversed IPSP. The IPSP was decreased in amplitude by hyperpolarizing current injection. Combined stimulation of the MLR and the ipsilateral high-threshold muscle or cutaneous afferents produced facilitation of both short- and long-latency MLR-evoked PSPs, suggesting that the two pathways share common interneurons. The possibility that the long-latency PSPs are produced by rapid oscillation in the locomotor central pattern generator is discussed. We concluded that MLR stimulation that evokes fictive locomotion produces both excitation and inhibition of spinal motoneurons. Spinal interneuronal systems are implicated and may be those involved in the initiation and control of locomotion. The probable relay sites for the descending pathway from the MLR to motoneurons are discussed.     

Excitatory effects of ACPD receptor activation in the hippocampus are mediated by direct effects on pyramidal cells and blockade of synaptic inhibition.

1. Phosphoinositide hydrolysis-linked excitatory amino acid (EAA) receptors (ACPD receptors) are selectively activated by the glutamate analogue trans-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD). Regional analysis of trans-ACPD-induced phosphoinositide hydrolysis indicates that this response is greater in the hippocampus than in other brain regions. Therefore we designed a series of studies aimed at testing the hypothesis that activation of this receptor modulates synaptic function in the hippocampal region. 2. We report that trans-ACPD dramatically altered field population spikes at each of the three major synapses in the hippocampal trisynaptic circuit at concentrations that are effective in activating phosphoinositide hydrolysis. At the perforant path-dentate gyrus synapse, bath application of trans-ACPD resulted in a decrease in the amplitude of field population spikes. In contrast, trans-ACPD markedly enhanced field population spike amplitude at the mossy fiber-CA3 synapse and the Schaffer collateral-CA1 synapse. In area CA1, but not area CA3, trans-ACPD also induced generation of multiple population spikes. 3. Simultaneous field potential recordings from the s. pyramidale and s. radiatum in area CA1 revealed that the effect of trans-ACPD on population spikes in this region was not accompanied by an increase in the initial slope of the field EPSP. This suggests that the effect of trans-ACPD was not mediated by a presynaptic action but must be mediated by direct effects on CA1 pyramidal cells or by a decrease in synaptic inhibition. 4. trans-ACPD had a number of direct excitatory effects on CA1 pyramidal cells. These included 1) cell depolarization (with an increase in input resistance), 2) inhibition of the slow afterhyperpolarization, and 3) blockade of spike frequency adaptation. trans-ACPD also had effects on CA1 pyramidal cells that were not excitatory in nature. These included an increase in the threshold for initiation of calcium spikes and an increase in interspike interval during prolonged current injection. None of these effects were mimicked by an ACPD analogue that does not activate the ACPD receptor (trans-methanoglutamate), nor were they blocked by kynurenate, a nonselective EAA receptor antagonist that does not block the ACPD receptor.(ABSTRACT TRUNCATED AT 400 WORDS)     

Calcium and sodium ions as charge carriers in the action potential of an identified snail neurone.

1. The soma of cell A in Helix aspersa produced action potentials in sodium-free or calcium-free saline, but not in saline with neither sodium nor calcium. 2. The axon had a sodium-dependent action potential. 3. Tetrodotoxin (5 x 10(-6) M) had no effect on the overshoot except at low external divalent ion concentrations. 4. The action potential in sodium-free saline was blocked by cobalt. 5. The slope of action potential overshoot against sodium concentration in the presence of 10 mM calcium was 10.5 mV/tenfold change. That of overshoot against calcium concentration in the presence of 75 mM sodium was 22 mV/tenfold change. 6. In sodium-free saline the slope of overshoot versus calcium concentration was 27 mV/tenfold change. 7. It is concluded that calcium is an important charge carrier in the action potential of cell A.     

Presynaptic inhibition produced by an identified presynaptic inhibitory neuron. II. Presynaptic conductance changes caused by histamine

We have examined the morphology and pharmacology of the L32 neurons, identified cells that mediate presynaptic inhibition in the Aplysia abdominal ganglion, to gain insight into the putative transmitter released by the L32 cells. We analyzed the fine structure of the synaptic release sites of L32 cells stained with horseradish peroxidase. Each varicosity of L32 was found to contain two general classes of vesicles. One class of vesicles is large (mean long diameter of 98 nm) and contains an electron-dense core that typically filled or nearly filled each vesicle profile. The second class of vesicles is smaller (mean long diameter of 67 nm) and relatively electron lucent. The size, distribution, and morphology of the vesicle population in L32's terminals was similar to that described at the synapses of the identified histaminergic neuron C2 in Aplysia (2). These morphological observations suggested that L32 cells might be histaminergic. Among the various putative transmitters tested, histamine was most effective in mimicking the postsynaptic effects of L32 cells onto L10, and onto other follower cells of L32 in the abdominal ganglion. Histamine also caused inhibition of transmitter output from L10. Both the IPSP produced by L32 in L10 and the response of L10 to histamine could be reversibly blocked by cimetidine, a histamine antagonist in Aplysia (14). These results support, but do not establish the identification of histamine as the putative transmitter of L32 cells. Histamine mimics the action of L32 in mediating presynaptic inhibition allowing us to examine in more detail the conductance changes in L10 underlying presynaptic inhibition. Voltage-clamp analysis revealed that histamine blocked the voltage-dependent Ca2+ current and increased a voltage-dependent K+ current in L10, much as did L32. Both of these changes are likely to act synergistically to inhibit transmitter release. Reduction of Ca2+ current in L10 would directly inhibit transmitter release from L10 directly by decreasing the amount of Ca2+ entering during spike depolarization. The increase in K+ current would act indirectly to reduce transmitter release from L10, by hyperpolarizing L10 and decreasing the amplitude and duration of spikes in L10, as well as reducing the steady-state Ca2+ influx. These results support the idea that in Aplysia presynaptic inhibition is caused primarily by a direct transmitter-mediated reduction in presynaptic Ca2+ current and secondarily by a hyperpolarization of the presynaptic neuron due to a transmitter-mediated increase in a K+ current.(ABSTRACT TRUNCATED AT 400 WORDS)     

Excitatory synaptic transmission mediated by NMDA and non-NMDA receptors in the superficial/middle layers of the epileptogenic human neocortex maintained in vitro.

Conventional intracellular recordings were made from regular-spiking cells located in layers II-IV to examine the involvement of excitatory amino acid receptors in synaptic transmission in epileptogenic human neocortical slices maintained in vitro. Extracellular stimuli that were below the threshold for generating action potentials evoked an excitatory postsynaptic potential (EPSP) with short latency to onset (0.8-4 ms). When suprathreshold stimuli were delivered, 95% of the neurons fired a single action potential. In 5% of the population, however, an all-or-none bursting discharge was observed. The EPSP and the bursting discharge were tested with the N-methyl-D-aspartate (NMDA) antagonist 3-((+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP, 5 microM) or the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 4 microM). In the presence of CNQX the peak amplitude of the EPSP was reduced by 85% and the bursting discharge was abolished completely. By contrast, CPP reduced the peak amplitude of the EPSP by 52%, attenuated the late phase of the bursting discharge and increased its threshold. These results indicate that excitatory amino acids function as excitatory transmitters in the human brain. While the involvement of non-NMDA receptors in the EPSP is in line with data from normal neocortical slices of other mammals, the participation of NMDA-mediated conductances to the EPSP appears peculiar to the epileptogenic human neocortex. This evidence, together with the contribution of NMDA and non-NMDA receptors to the all-or-none bursting discharge suggests that excitatory amino acid-mediated transmission might be modified in the epileptogenic human neocortex.     

Non-cholinergic synaptic potentials mediated by lumbar colonic nerve in the guinea-pig inferior mesenteric ganglion in vitro

Non-cholinergic slow synaptic potentials mediated by the lumbar colonic nerve have been investigated using an in vitro preparation of the guinea-pig inferior mesenteric ganglion attached to a distal colonic segment. Non-cholinergic potential responses to colonic nerve stimulation, colonic distension and chemical activation of sensory afferents were recorded intracellularly from neurons in the inferior mesenteric ganglion. Electrical stimulation of the lumbar colonic nerve produced either a slow excitatory postsynaptic potential, or a slow inhibitory postsynaptic potential followed by a slow excitatory postsynaptic potential. The extrapolated reversal potential of the slow excitatory postsynaptic potential was in the range of 0 to -20 mV and that of the slow inhibitory postsynaptic potential was -90 to 110 mV. The slow excitatory postsynaptic potential and the slow inhibitory postsynaptic potential were reversibly abolished by perfusion of the ganglion with tetrodotoxin (1 microM), or perfusion with low calcium (200 microM), high magnesium (12 mM) containing solution. Capsaicin (1 microM) evoked a reversible depolarization of inferior mesenteric ganglion cells after which desensitization occurred and the slow excitatory postsynaptic potential was abolished but the slow inhibitory postsynaptic potential was enhanced in amplitude and prolonged in duration. Bath application of substance P (2 microM) evoked a prolonged depolarization of inferior mesenteric ganglion neurons, during which the slow excitatory postsynaptic potential but not the slow inhibitory postsynaptic potential was abolished. Distensions of the colon to pressures in the range of 2-25 cm of water produced a stimulus graded non-cholinergic slow depolarization which was occasionally followed by a late slow hyperpolarization. Both types of response were abolished by tetrodotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of the GABA uptake inhibitor tiagabine on inhibitory synaptic potentials in rat hippocampal slice cultures.

1. The effects of the gamma-aminobutyric acid (GABA) uptake blocker tiagabine on inhibitory synaptic potentials (IPSPs) were examined with microelectrode and whole-cell recording from CA3 pyramidal cells in rat hippocampal slice cultures. 2. Tiagabine (10-25 microM) greatly prolonged the duration of monosynaptic IPSPs elicited in the presence of excitatory amino acid antagonists but had no effect on their amplitude. Part of the prolonged time course resulted from a GABAB receptor-mediated component that was not detectable under control conditions. 3. The mean decay time constant of the underlying GABAA receptor-mediated synaptic current was increased from 16 to 250 ms. Spontaneous miniature IPSPs recorded with whole-cell clamp were unaffected by tiagabine. Pentobarbital sodium, in contrast, increased the decay time constant of both evoked and spontaneous GABAA-mediated currents. 4. Tiagabine (25 microM) inhibited spontaneous and evoked epileptiform bursting induced by increasing the extracellular potassium concentration to 8 mM. 5. We conclude that GABA uptake plays a significant role in determining the time course of evoked IPSPs and also limits the likelihood that GABAB receptors are activated.     

A dopaminergic inhibitory postsynaptic potential mediated by an increased potassium conductance

Intracellular recordings from intact pituitary melanotrophs show that, in the same cell, inhibitory postsynaptic potentials resulting from either pituitary stalk stimulation or exogenous dopamine are abolished by D2 receptor antagonists, display identical conductance changes, are reversed in polarity at the same membrane potential and are sensitive to pertussis toxin pretreatment. The reversal potential of the inhibitory postsynaptic potential shows a 65 mV shift with a 10-fold change in external potassium concentration, which is close to that predicted by the Nernst equation. We conclude that activation of this synapse releases dopamine which acts on a D2 receptor to increase potassium conductance via a G-protein-mediated mechanism. This is the first characterization of an inhibitory dopaminergic synapse in the mammalian nervous system.     

Ultrastructure of the terminals of an identified 5-hydroxytryptamine-containing neurone marked by intracellular injection of radioactive 5-hydroxytryptamine

Summary The axons and terminal processes of an identified 5-hydroxytryptamine-containing neurone were located for study with the electron microscope. Tritiated 5-hydroxytryptamine was injected into the neurone's cell body, and after allowing time for the radioisotope to pass along the processes of the neurone, tissue was examined by electron microscope autoradiography. Terminal processes were observed at approximately 1 cm from the injected cell body, in areas of the nervous system where previous electrophysiological work had shown the presence of postsynaptic neurones. Dense-cored vesicles of mean diameter 100 nm were observed in the axons and terminal processes of the neurone. The terminal processes also contained aggregates of clear vesicles of mean diameter 65 nm. Structures resembling lysosomes, which were frequently labelled, were present in the axons of the neurone. No membrane specializations associated with typical synapses were observed.