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A Bonci

Publications and source records attributed to A Bonci.

At least 37 records · Page 2Linked to original sources
PubMed1997

Glutamate metabotropic receptor agonists depress excitatory and inhibitory transmission on rat mesencephalic principal neurons.

Intracellular and whole-cell patch-clamp recordings were used to evaluate the actions of different metabotropic glutamate receptor (mGluR) agonists on the synaptic inputs evoked on principal cells of the rat mesencephalon. Bath application of the group III mGluR agonists L-2-amino-4-phosphonobutyric acid (L-AP4) and L-serine-O-phosphonobutanoate (L-SOP) did not change the holding current of the cells held at resting potential (-60 mV) but produced a dose-dependent inhibition of the amplitude of the excitatory and inhibitory events. L-AP4 and L-SOP were more effective at inhibiting the excitatory postsynaptic currents (EPSCs) than the GABA(A) and GABA(B) inhibitory postsynaptic currents (IPSCs). The suppressing effects of L-AP4 and L-SOP were antagonized by (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP-4) but not by +/- -alpha-methyl-4-carboxyphenylglycine (MCPG). Moreover, the group II agonist (2S,1'S,2'S)-(carboxycyclopropyl)glycine (L-CCG1) and the group I agonist (RS)-3,5-dihydrophenylglycine (3,5-DHPG) depressed in a dose-related manner the EPSC, the GABA(A) IPSC and the GABA(B) IPSC. The suppressing effect of the two mGluRs agonists was partially antagonized by MCPG but not by MAP-4. In addition, both L-CCG1 and 3,5-DHPG caused an inward shift of the holding current. To characterize the site of action of the metabotropic receptor agonists, experiments were performed to examine the amplitude and ratio of EPSC and GABA(A) IPSC pairs. The increase of the s2/s1 ratio caused by the agonists suggests that the location of the inhibitory mGluRs was presynaptic. These results indicate that the activation of presynaptic mGluRs controls the release of excitatory and inhibitory transmitters on presumed dopaminergic cells within the ventral mesencephalon.

Animals↗
PubMed1996

A common mechanism mediates long-term changes in synaptic transmission after chronic cocaine and morphine.

The mesolimbic system is known to play a role in self-administration of opioids and psychostimulants. Although morphine and cocaine act by separate cellular mechanisms initially, the present study describes a common change in synaptic regulation of dopamine cells in the ventral tegmental area 1 week after termination of chronic treatment with either drug. Normally, D1 receptor activation augmented the amplitude of a gamma-aminobutyric acid type B (GABA(B)) inhibitory postsynaptic potential (IPSP), but in drug-experienced animals, D1 receptor activation caused an inhibition of the GABA(B) IPSP. The inhibition was blocked by adenosine A1 receptor antagonists and by agents that disrupted the metabolism of cAMP. This long-lasting dopamine-adenosine interaction may be one mechanism involved in dopamine-mediated craving and relapse to drug-seeking behaviors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1996

Characterization of a barium-sensitive outward current following glutamate application on rat midbrain dopaminergic cells.

Using intracellular electrophysiological recordings in dopaminergic (principal) neurons of the rat mesencephalon maintained in vitro, we studied a postexcitatory amino acid response (PEAAR). Under current-clamp mode, bath application of glutamate produced a depolarization that was followed by a hyperpolarization when the perfusion of the excitatory amino acid was discontinued. Under single-microelectrode voltage-clamp mode, an outward current followed the glutamate-induced inward current. The PEAAR was associated with an increase in membrane conductance and reversed polarity at about-85 mV (2.5 mM extracellular K+). The null potential for the PEAAR was independent of the intracellular loading of chloride ions and was shifted towards less negative values (approximately 23 mV) by increasing extracellular K+ from 2.5 to 8.5 mM. The PEAAR was present in neurons treated with tetraethylammonium (5-10 mM), apamin (1 microM) or glibenclamide (1-300 microM). However, it was strongly depressed or blocked by extracellular barium (300 microM to 1 mM), by low-calcium (0.5 mM) plus cadmium (100 microM) or magnesium (10 mM), and by low-sodium solutions. An outward response was also generated after an inward current induced by the perfusion of the specific agonists for the ionotropic excitatory amino acid receptors NMDA, alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) and kainate. The PEAAR was not affected by tetrodotoxin (1 microM), saclofen (100-300 microM), bicuculline (30 microM), sulpiride (1 microM) or strychnine (1 microM). In addition, the inhibition of the ATP-dependent Na(+)-K+ pump by ouabain and strophanthidin (1-10 microM) prolonged the glutamate-induced membrane depolarization/inward current while the subsequent PEAAR was reduced or not observed. Our data indicate that the PEAAR mainly results from the activation of a barium-sensitive potassium current. This response might limit the excitatory and eventually neurotoxic effects of glutamate.

Animals↗
PubMed1996

Electrophysiological effects of monoamine oxidase inhibition on rat midbrain dopaminergic neurones: an in vitro study.

1 The effects of the inhibition of monoamine oxidase (MAO) type A and B have been evaluated on the spontaneous firing activity of the dopaminergic (principal) neurones of the rat midbrain intracellularly recorded from a slice preparation. 2 The non-specific MAO inhibitor, pargyline, superfused at a concentration of 10-100 microM, decreased or abolished the spontaneous firing discharge of the principal neurons in the subtantia nigra pars compacta and ventral tegmental area. This effect had a slow onset and appeared to be sustained. 3 The administration of the dopamine D2/3 receptor antagonist, sulpiride (100-300 nM), antagonized the pargyline-induced effect, while the superfusion of the dopamine D1 receptor antagonist, SCH 23390 (1-3 microM) did not counteract the induced inhibition of the firing rate. 4 The inhibitor for the MAO A, clorgyline (30-100 microM), reduced the firing rate of the dopaminergic neurones. A similar depressant effect was also observed when a MAO B inhibitor, deprenyl (30-100 microM), was applied. Lower concentrations of both drugs (300 nM-10 microM) did not produce consistent effects on neuronal discharge. 5 Our data suggest that only the blockade of both types of MAO enzymes favours the inhibitory action of endogenous dopamine on somato-dendritic D2/3 autoreceptors.

Animals↗
PubMed1995

Actions of glycine on non-dopaminergic neurons of the rat substantia nigra.

The effects of glycine on non-dopaminergic cells in rat substantia nigra pars compacta and pars reticulata maintained in vitro were investigated using intracellular recording techniques. Glycine, superfused at a concentration between 30 microM and 1 mM, reversibly blocked the spontaneous firing of these neurons. The inhibition of firing discharge was associated with a hyperpolarization of the membrane (potassium acetate-filled electrodes) and an increase in conductance. Under voltage-clamp experiments (holding potential between -57 and -65 mV), glycine produced an outward response which reversed polarity at about -74 mV. However, when the recording electrodes were filled with KCl, the glycinergic response was mainly depolarizing/inward and reversed at about -43 mV. Thus, it appeared to be due to an increase in chloride permeability. Furthermore, the effects of glycine were reversibly antagonized by strychnine (between 300 nM and 1 microM). Our findings demonstrate that glycine is a potent inhibitory agent on non-dopaminergic cells of the substantia pars compacta and par reticulata that acts by activating strychnine-sensitive receptors.

Animals↗
PubMed1995

Properties of the hyperpolarization-activated cation current Ih in rat midbrain dopaminergic neurons.

Intracellular electrophysiological recordings in current- and voltage-clamp mode were obtained from dopaminergic neurons of the rat mesencephalon in an in vitro slice preparation. In current-clamp mode, a time-dependent anomalous rectification (TDR) of the membrane was observed in response to hyperpolarizing current pulses. In single-electrode voltage-clamp mode, a slowly developing inward current (Ih) underlying the TDR was studied by hyperpolarizing voltage commands from a holding potential of -50 to -60 mV. Ih started to be activated at approximately -69 mV, was fully activated at -129 to -141 mV, with half-maximal activation at -87 mV, and showed no inactivation with time. The time course of development of Ih followed a single exponential, and its time constant was voltage-dependent. At -81 mV, Ih activated with a time constant of 379 +/- 47.6 ms, whereas at -129 mV Ih activated with a time constant of 65 +/- 2.2 ms. Its estimated reversal potential was -35 +/- 4 mV. Raising the extracellular concentration of K+ from 2.5 to 6.5 and to 12.5 mM increased the amplitude of Ih while reducing the extracellular concentration of Na+ from 153.2 to 27.2 mM caused a reduction in amplitude of Ih. Bath application of caesium (1-5 mM) reversibly reduced or blocked the TDR/Ih. Perfusion of tetrodotoxin (0.5-1 microM), tetraethylammonium (10-20 mM) or barium (0.3-2 mM) did not significantly affect Ih. Ih was also present in cells impaled with CsCl-filled electrodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Outward potassium currents activated by depolarization in rat globus pallidus.

Voltage-dependent potassium currents play a key role in shaping the firing pattern of central neurons. Their pharmacological and physiological identification is rather important in the structures which are involved in the filtering of input/output messages. In this regard, globus pallidus external segment (GPe) is indicated as a crucial station in the well-known indirect pathway of the basal ganglia. Among the potassium conductances which have been indicated to condition the firing behavior and the neuronal integrative properties in many central neurons, we analysed the depolarization-activated ones by means of patch-clamp recordings in the whole-cell configuration. Two main families of calcium-independent outward potassium currents are activated by depolarization in GPe neurons acutely isolated from the adult rat. From depolarized holding potentials (-50/-45 mV), a slowly-activating, sustained current is evoked; it manifests very little inactivation and it is available at rather depolarized potentials (-30 mV/-20 mV). This current is relatively resistant to 4-aminopyridine (4-AP) but it is blocked by tetraethilammonium ions (TEA) and consequently it resembles delayed rectifier current (Ik). From negative holding potentials (-80/-100 mV), on the other hand, A-like conductances are activated. Together with a fast-inactivating transient current, another component is observed in a significant proportion of recordings (45%). This current shows half-inactivation voltage around -90 mV, peculiar sensitivity to micromolar doses of 4-AP and a slow rate of recovery from inactivation. The presence and the modulation of these A-like currents may be a very critical aspect in the membrane physiology of pallidal neurons.

4-Aminopyridine↗
PubMed1995

Electrophysiology of dopamine D-1 receptors in the basal ganglia: old facts and new perspectives.

1. The dopamine (DA) D1-receptor family is highly represented in the mammalian brain and particularly in the nigrostriatal system, whose integrity is crucial for the execution of motor performances. 2. In the last decade, our understanding of the electrophysiology of D1 receptors on caudate-putamen neurons has greatly improved. The effects of the activation of striatal D1 receptors were studied by extracellular single unit recordings in the intact animal as well as by intracellular recordings in rat brain slice preparation. More recently, whole-cell recordings on isolated striatal neurons have further addressed this issue and confirmed the inhibitory modulatory role of D1 receptor on the electrical activity of striatal neurons. 3. Several important questions, however, concerning the functional effects of D1 receptor activation in the basal ganglia are still debated: the cellular segregation of the distribution of D1-D2-like receptors, their synergistic or opposite functional roles at the second messenger level, the effects of D1 receptor activation on the transmitter release and the modifications of D1 receptor pharmacology in dopamine-denervated striata. 4. A different perspective will also be discussed: the involvement of D1 receptors in long-term changes of synaptic efficacy in the striatum as a possible correlate of motor learning.

Animals↗
PubMed1995

The modulation of dopamine receptors in rat striatum.

In the last decades, the contribution given by basic electrophysiology to the understanding of the nigrostriatal pathway in mammals has been rather important. The main results obtained by our group will be revised in this short review. The most common responses produced by dopamine (DA) on the principal striatal cells (the medium spiny neurons) are the modulation of the corticostriatal synaptic transmission and the decrease of voltage-dependent inward conductances. After blockade of DA transmission, both spontaneous and cortically driven glutamatergic postsynaptic potentials were inhibited by the selective activation of DA D2 receptors. In naive animals, the DA-mediated inhibition of postsynaptic firing activity was mediated by D1 receptor activation. Nevertheless, the two main subclasses of DA receptors seemed to cooperate in the formation of the long-term depression (LTD) of excitatory synaptic transmission in the striatum. The excitotoxic hypothesis of neurodegeneration has further stimulated our interest towards the study of the interactions between DA and other neurotransmitters into the basal ganglia.

Animals↗
PubMed1994

Responses of rat mesencephalic dopaminergic neurons to a prolonged period of oxygen deprivation.

We employed intracellular electrophysiological techniques to examine the effects of a prolonged anoxia (more than 7 min superfusion with artificial cerebrospinal fluid saturated with 95% N2-5% O2) on dopaminergic neurons of the rat ventral mesencephalon maintained in vitro. A prolonged anoxia caused an inhibition of the spontaneous firing and a sustained (mean 16 min) and slowing declining hyperpolarization of the membrane in 30 dopaminergic cells. This was associated with a decrease of the apparent input resistance at 5, 10, 15 and 20 min of O2 deprivation by 38% (n = 18), 42% (n = 8), 48% (n = 18) and 54% (n = 8) of control, respectively. The continuation of anoxia, 1-4 min after the hyperpolarizing period, induced an irreversible depolarization (n = 8). More than 50% of the cells (17 of 30) fully recovered their electrophysiological properties after 15 min of O2 deprivation. Since the intracellular diffusion of cesium (a potassium channel blocker) was able to block the hyperpolarization and to reveal a depolarization caused by anoxia, we tested whether the blockade of the hyperpolarization modified the resistance of the cells to O2 deprivation. We observed that the cells loaded with cesium were depolarized and damaged in a period of O2 deprivation less than 10 min. The apparent input resistance of these neurons was irreversibly reduced by 36% of the control at 5 min of anoxia (n = 6). Furthermore, in order to ascertain whether an impairment of the sodium/potassium pump due to energy failure is involved in the anoxia-induced depolarization, we blocked the Na+/K+ ATPase pump with the inhibitor ouabain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effects of dihydropyridine calcium antagonists on rat midbrain dopaminergic neurones.

1. The effects of the dihydropyridine calcium channel antagonists, nifedepine and nimodipine (300 nM-30 microM) were tested in vitro on intracellularly recorded dopaminergic neurones in the rat ventral mesencephalon. 2. Bath applied nifedipine and nimodipine inhibited in a concentration-dependent manner the spontaneous firing discharge of the action potentials, whereas, the dihydropyridine calcium channel agonist, Bay K 8644 increased the firing rate. 3. Pacemaker oscillations and bursts of action potentials were produced by loading the cells with caesium. Nifedipine and nimodipine reduced the rate and the duration of the caesium-induced membrane oscillations and decreased the number of action potentials in a burst. During the blockade of potassium currents the dopaminergic neurones often developed a prolonged (100-800 ms) afterdepolarization that was also inhibited by dihydropyridines. 4. The spontaneous discharge of calcium spikes was also inhibited by both dihydropyridine calcium antagonists. The apparent input resistance and the level of membrane potential were not affected by the dihydropyridine calcium antagonists. 5. If the action potential duration was less than 150 ms the shape of the spike was not clearly influenced by both calcium antagonists. However, when the duration of the action potential was longer than 150-200 ms due to the intracellular injection of caesium ions plus the extracellular application of tetraethylammonium (10-50 mM), both nifedipine and nimodipine reversibly shortened the plateau potential. 6. It is suggested that nifedipine and nimodipine depress the rhythmic and bursting activity of the dopaminergic cells and shorten the calcium action potential by blocking dihydropyridine-sensitive high-threshold calcium currents.

Action Potentials↗
PubMed1994

Effects of anoxia on rat midbrain dopamine neurons.

1. Dopamine-containing neurons of the rat midbrain were recorded intracellularly in vitro. Anoxia (2-5 min) caused reversible membrane hyperpolarization (4-25 mV), which blocked spontaneous firing of action potentials. Under voltage clamp, anoxia produced an outward current (100-1,000 pA) associated with an increase in the apparent input conductance. 2. The mean reversal potential of the anoxia-induced response at 2.5 and 12.5 mM [K+] was -86 and -66 mV, respectively. 3. The effect of anoxia was not blocked by tetrodotoxin (TTX), saclofen, (-)sulpiride, or strychnine. Superfusate containing low calcium (0.5 mM CaCl2 and 10 mM MgCl2 or 0.5-1 mM CaCl2 and 1 mM CoCl2) or low sodium (25-40% of control) reduced the anoxia-induced outward current. 4. Extracellular barium (0.1-1 mM) blocked the anoxia-induced hyperpolarization/outward current. Other K+ channel blockers (tetraethylammonium, apamin, quinine, and glibenclamide) failed to reduce anoxia-induced current. 5. When the dopamine-containing neurons were loaded with cesium (1-2 mM), anoxia caused a reversible membrane depolarization and a block of the firing activity. This depolarization was voltage dependent; it was decreased or blocked by the hyperpolarization of the membrane. 6. Perfusion of the cells with 0.5-1 microM TTX did not affect the membrane depolarization/inward current caused by anoxia. These were also present when the cells were treated with the excitatory amino acid receptor antagonists D,L-2-amino-5-phosphonovalerate (APV) (30 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10 microM). 7. The exposure of the neurons with low-sodium, low-calcium solutions reversibly reduced the depolarizing/inward effects of anoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1994

Primary bronchial malignant melanoma. A case report.

A case of primary bronchial malignant melanoma occurred in a 66 years old woman is reported. Because of cough and hemoptysis bronchoscopic examination was performed and and a polypoid mass was found to occlude the right lower bronchus. Histopathologic examination showed the presence of malignant melanoma also confirmed by immuno reactivity with antibodies to S-100 protein and melanoma associated monoclonal antibody HMB45. Clinical history, physical examination and other instrumental investigations failed to find other possible primary sites of the tumour. Primary melanoma of the lung is a very rare condition, but our case seems to satisfy the criteria to be considered in the little group of definite primary melanoma of the lower respiratory tract.

Aged↗
PubMed1993

Characterization of immunoreactive octapeptides of human-cytomegalovirus gp58.

We have mapped continuous epitopes, for positions 591-673 of the human cytomegalovirus 58-kDa glycoprotein using overlapping synthetic peptides and human sera. This region contains a fragment previously described as including the dominant site for induction of human-cytomegalovirus antibodies. Since the selected sequence is highly conserved among herpes viruses, we have considered the possible presence of antigenic cross-reactivity, particularly with the Epstein-Barr virus. Several peptides in the studied region were antigenic and two main continuous epitopes have been identified. Serological cross-reactions observed with Epstein-Barr virus are discussed, focusing on the possible implications of structural features and sequence similarity between human-cytomegalovirus and Epstein-Barr-virus glycoproteins.

Amino Acid Sequence↗
PubMed1993

Activation of metabotropic glutamate receptors induces an inward current in rat dopamine mesencephalic neurons.

To investigate the electrophysiological effects of the stimulation of the metabotropic excitatory amino acid receptors, we applied trans-1-amino-cyclopentane-1,3-dicarboxylate, an agonist of this type of receptors, on presumed rat dopamine cells intracellularly recorded in vitro. Trans-1-amino-cyclopentane-1,3-dicarboxylate (3-30 microM, t-ACPD) caused a sustained increase of the spontaneous firing rate and a depolarization. When the membrane potential was held at about the resting level (-50, -60 mV), by the single-electrode voltage-clamp technique, t-ACPD induced an inward current. In 57% of the tested cells the inward current was associated with a decrease of the apparent input conductance. In the remaining cells no obvious changes in membrane conductance were observed. The active form of t-ACPD, (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylate [3-50 microM, (1S,3R)-ACPD] also produced a reversible inward current on the dopaminergic cells and this was antagonized by (S)-4-carboxy-3-hydroxyphenylglycine (300 microM), a selective antagonist of the (1S,3R)-ACPD-induced depolarization on central neurons. The (1S,3R)-ACPD-induced inward current was not antagonized by L-2-amino-3-phosphonopropionic acid (100 microM), an antagonist of the t-ACPD-induced activation of inositide synthesis. 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM), an alfa-amino-3-hydroxy-5- methyl-isoxazole propionic acid/kainate antagonist, DL-amino-5-phosphonopentanoic acid (30 microM), an N-methyl-D-aspartate antagonist, and scopolamine (10 microM), a muscarinic antagonist, did not significantly affect the actions of t-ACPD. A block of synaptic transmission obtained by applying tetrodotoxin failed to prevent the action of t-ACPD.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1993

Differential rates of forgetting from long-term memory in Alzheimer's and multi-infarct dementia.

In this study we explored the rate of forgetting from long-term memory in Alzheimer's (AD) and multi-infarct (MID) dementia. For this purpose, we administered to 15 AD, 15 MID, and 22 control subjects two tasks exploring, respectively, long-term verbal and long-term visuo-spatial memory. The absolute rate of forgetting in both tasks was computed as the difference between immediate and delayed recall of memorandum. Since level of immediate recall was significantly different between groups, a proportional rate of forgetting (percentage of memorandum lost passing from immediate to delayed recall) was computed for each patient. In the verbal task (Rey's 15 words) AD patients displayed significantly larger absolute and proportional rates of forgetting than MID and control subjects. In the spatial task (Corsi block supraspan), the absolute rate of forgetting was only marginally different between groups. Nevertheless, AD patients demonstrated a larger proportional rate of forgetting than MID and normal subjects. These results point out an exalted decay of information from long-term memory store in AD patients. In the light of previous data (Corkin et al., 1984; Kopelman, 1985) we propose that long-term memory deficits in AD is due, at least in part, to an abnormal forgetting of information within the first few minutes following acquisition. Information still present in the subsequent period (10 min to several days) is retained normally. The normal rate of forgetting in MID patients, further, suggests different mechanisms underlying memory disorders in vascular and degenerative dementias.

Aged↗
PubMed1993

Responses of vestibular neurons to stimulation of cortical sensorimotor areas in the cat.

Selected areas of sensorimotor cortex were stimulated with short trains adequate to evoke focal movements. Neurons belonging to the vestibular nuclear complex, including the lateral vestibular nucleus (LVN), were mainly affected by the stimulation of wrist-elbow, shoulder and cortical areas. The units responded to cortical stimulation either with a constant latency lower than 10 msec (short-latency units), or with variable latencies higher than 10 msec (long-latency units). Particular attention was paid to the first group of responses showing the involvement of direct and/or oligosynaptic facilitatory inputs from the cortical cells. Moreover, many of these responsive vestibular nuclear neurons were identified as projecting to the spinal cord.

Anesthesia↗