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V Crunelli

Publications and source records attributed to V Crunelli.

At least 19 recordsLinked to original sources
PubMed1992

Detecting changes in neuronal activities induced by N-methyl-D-aspartate receptor blockade using non-linear dynamics techniques.

The dynamics of N-methyl-D-aspartate receptor blockade-induced transitions between two types of intracellularly recorded spontaneous membrane potential oscillation from cat thalamic neurons have been studied using non-linear dynamics techniques. We report that, as previously predicted by theoretical studies, the number of degrees of freedom of these oscillations (the minimal number of independent variables governing the activity) is small, i.e. they are low dimensional. The N-methyl-D-aspartate receptor antagonists DL-2-amino-5-phosphono-valeric acid and ketamine, which transformed one type of oscillation into another, decreased the calculated dimension. DL-2-Amino-5-phosphono-valeric acid had no effect on the dimension when Mg2+ was present in the perfusion medium. The decrease in dimension was gradual and its time-course had a sigmoidal shape. It is suggested that the application of the machinery of dynamical systems theory might help to detect and monitor drug-induced membrane potential state transitions and to identify the factors underlying membrane potential oscillations.

2-Amino-5-phosphonovalerate↗
PubMed1992

Computer simulation of the pacemaker oscillations of thalamocortical cells.

Computer simulations of the spontaneous pacemaker oscillations observed in thalamocortical (TC) cells were performed using a biophysical model that included the low voltage activated, Ca2+ current, IT, and the mixed Na+/K+, inward rectifying current, Ih. The simulations accurately reproduced the waveform and voltage-dependence of the pacemaker oscillations, hence the transition from tonic firing to burst firing which is a peculiar feature of the electrical activity of TC cells both in vivo and in vitro. The results provide further support to the suggestion that IT and Ih are essential for the presence of the pacemaker oscillations, and indicate that our model is a useful tool for the study of spontaneous, low-frequency oscillatory activities in TC cells.

Animals↗
PubMed1992

A role for low-frequency, rhythmic synaptic potentials in the synchronization of cat thalamocortical cells.

1. Low-frequency, rhythmic synaptic potentials and their ability to evoke and modulate membrane potential oscillations in thalamocortical (TC) cells of the cat dorsal lateral geniculate nucleus (dLGN) were investigated using intracellular recordings in a brain slice preparation. Three types of rhythmic synaptic potentials were distinguished: EPSPs, IPSPs and 'complex synaptic potentials' consisting of an IPSP followed by an EPSP. 2. The frequency of all three types of synaptic potentials was insensitive to changes in the membrane potential. At potentials positive to -50 mV, the EPSPs and the complex potentials gave rise to action potentials, while between -65 and -80 mV all three types of synaptic potential evoked low-threshold Ca2+ potentials. TC cells which displayed rhythmic synaptic potentials were either cells that showed spontaneous pacemaker oscillation or cells that were brought to oscillate by the rhythmic EPSPs or depolarizing (i.e. reversed IPSPs. 3. The low-frequency (1.9 +/- 0.2 Hz), rhythmic EPSPs were observed in 23 (out of 192) cells, were abolished by tetrodotoxin (TTX; n = 4) and by the combined application of DL-2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione (n = 3), and were insensitive to bicuculline (n = 4). Paired intracellular recordings (n = 32) demonstrated the presence of simultaneously occurring EPSPs in a pair of cells situated 75 microns apart. 4. The low-frequency (2.2 +/- 0.3 Hz), rhythmic IPSPs were observed in 5 (out of 192) cells, were blocked by bicuculline (n = 3), and reversed in polarity at -65 mV. The low-frequency (1.3 +/- 0.3 Hz), rhythmic 'complex potentials' were observed in 5 (out of 192) cells and were abolished by TTX (n = 2). 5. Intracellular depolarizing current pulses delivered at different phases of the pacemaker oscillations revealed the existence of two different types of phase resetting. Furthermore, a current pulse of critical amplitude and duration applied at a specific phase of the cycle abolished the pacemaker oscillations. 6. These results indicate that the low-frequency, rhythmic synaptic potentials recorded in TC cells of the dLGN (i) originate from other TC cells that are in the pacemaker oscillating mode, (ii) are capable of driving other TC cells to oscillate rhythmically, or of modulating the frequency of pacemaker oscillations, and (iii) provide a means by which oscillatory activities of TC cells can be synchronized in the absence of sensory, cortical and reticular thalamic inputs.

Action Potentials↗
PubMed1991

A role for GABAB receptors in excitation and inhibition of thalamocortical cells.

Gamma-aminobutyric acid (GABA) in the thalamus has mainly been associated with the inhibitory modulation of the sensory and cortical flow of information via a 'classical', chloride-dependent, GABAA receptor-mediated action. However, the discovery of a late, long-lasting potassium-dependent inhibitory postsynaptic potential (IPSP) mediated by GABAB receptors present on thalamocortical cells, has allowed new insights into our understanding of the physiological role of this neurotransmitter. In particular, work on the dorsal lateral geniculate nucleus indicates that together with a relatively weak inhibition, GABAB receptor-mediated IPSPs 'prepare' thalamocortical cells for burst firing by activating low-threshold calcium potentials. Thus, GABA in the thalamus can no longer be viewed only as a 'classical' inhibitory transmitter but also as a neuromodulator with a 'priming' role for burst firing excitation. This dual role of GABAB receptors in inhibition and excitation of thalamocortical cells might allow different interpretations of earlier findings in animals and humans, both in healthy and pathological conditions. It will also help to identify new functions for postsynaptic GABAB receptors in other parts of the central nervous system.

Animals↗
PubMed1991

Low-frequency oscillatory activities intrinsic to rat and cat thalamocortical cells.

1. Low-frequency membrane potential oscillations recorded intracellularly from thalamocortical (TC) cells of the rat and cat dorsal lateral geniculate nucleus (dLGN) and of the rat ventrobasal nucleus (VB) maintained in vitro were investigated. On the basis of their electrophysiological and pharmacological properties, four types of activity were distinguished and named: the pacemaker oscillations, the spindle-like oscillations, the 'very slow' oscillations and the 'N-methyl-D-aspartate' (NMDA) oscillations. 2. The pacemaker oscillations (95 out of 173 cells) consisted of rhythmic, large-amplitude (10-30 mV) depolarizations which occurred at a frequency of 1.8 +/- 0.3 Hz (range, 0.5-2.9 Hz) and could often give rise to single or a burst of action potentials. Pacemaker oscillations were observed when the membrane potential was moved negative to -55 and positive to -80 mV, but in a given cell the upper and lower limits of this voltage range were separated by only 13.1 +/- 0.5 mV. Above -45 mV tonic firing consisting of single action potentials was seen in the cells showing this or the other types of low-frequency oscillations. 3. The spindle-like oscillations were observed in thirty-nine (out of 173) TC cells and consisted of rhythmic (2.1 +/- 0.3 Hz), large-amplitude depolarizations (and often associated burst firing) similar to the pacemaker oscillations but occurring in discrete periods every 5-25 s and lasting for 1.5-28 s. The spindle-like oscillations were observed when the membrane potential was moved negative to -55 and positive to -80 mV and in two cells they were transformed into continuous pacemaker oscillations by depolarization of the membrane potential to -60 mV. 4. Pacemaker and spindle-like oscillations were unaffected by tetrodotoxin (TTX) or by selective blockade of NMDA, non-NMDA, GABAA, GABAB, nicotinic, muscarinic, alpha- and beta-noradrenergic receptors. 5. The 'very slow' oscillations consisted of a TTX-insensitive, slow hyperpolarization-depolarization sequence (5-15 mV in amplitude) which lasted up to 90 s and was observed in nine dLGN cells and in two VB cells. The pacemaker and the spindle-like oscillations were recorded in one cell each which also showed the 'very slow' oscillations. 6. The 'NMDA' oscillations were observed only in a 'Mg(2+)-free' medium (0 mM-Mg2+, 2-4 mM-Ca2+; 64 out of 72 cells) and consisted of large-amplitude (10-25 mV) depolarizations that did not occur at regular intervals and were intermixed with smaller depolarizations present on the baseline and on the falling phase of the larger ones.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1991

Two inward currents and the transformation of low-frequency oscillations of rat and cat thalamocortical cells.

1. The contribution of a slow, mixed Na(+)-K+, inward rectifying current (Ih) and the T-type Ca2+ current (IT) (that underlies low-threshold Ca2+ potentials) to the low-frequency oscillations observed in rat and cat thalamocortical (TC) cells in vitro was studied using current clamp and single-electrode voltage clamp recordings. 2. From a holding potential of -50 mV, voltage steps negative to -60 mV showed the presence of a slow, non-inactivating inward current, Ih. This current was unaffected by Ba2+ (1-4 mM), tetrodotoxin (0.5-1 microM) and TEA (20 mM, n = 6), reversibly blocked by Cs+ (1-3 mM), and its reversal potential (-33.0 +/- 1.2 mV) followed changes in the extracellular Na+ and K+, but not Cl-, concentration. 3. Application of Cs+ (1-3 mM) abolished the pacemaker oscillations (n = 9), while in six cells that did not show any oscillatory activity Cs+ first evoked the spindle-like oscillations that, in the continuous presence of these ions, were then transformed into the pacemaker oscillations before all activities were finally blocked: all these effects were accompanied by a hyperpolarization and a progressive decrease and final blockade of Ih. Cs+ had no effect on the 'N-methyl-D-aspartate' (NMDA) oscillations (n = 5) and Ba2+ (2 mM, n = 8) did not block the pacemaker, the spindle-like and the 'NMDA' oscillations. 4. In ten cells that showed the pacemaker oscillations selective activation of beta-adrenoceptors by 10-50 microM-noradrenaline (in the presence of alpha-noradrenergic antagonists) or by 20 microM-isoprenaline first transformed the pacemaker oscillations into the spindle-like oscillations that, in the continuous activation of beta-receptors, were finally abolished: all these effects were accompanied by a depolarization and a progressive increase of Ih. 5. In TC cells that showed the pacemaker oscillations application of 1-octanol (50-100 microM), an antagonist of T-type Ca2+ currents, reversibly blocked this activity but concomitantly decreased (50%) the cell input resistance (n = 5). Application of Ni2+ (0.2-0.5 mM, n = 13), another antagonist of IT reversibly blocked the pacemaker, the spindle-like and the 'NMDA' oscillations. 7. In cells showing the pacemaker oscillations it was found that the current developing from the most hyperpolarized potential of an oscillation cycle was an inward relaxation whose time course differed from that of Ih evoked at the same potential.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Sleep-promoting action of excitatory amino acid antagonists: a different role for thalamic NMDA and non-NMDA receptors.

Changes in the sleep-waking cycle of freely moving cats were studied during application of excitatory amino acid antagonists in the ventro-posterolateral thalamic nuclei by microdialysis. DL-2-Amino-5-phosphono-pentanoic acid (APV), a selective N-methyl-D-aspartate (NMDA) receptor antagonist, produced an increase in the deep stages of slow wave sleep and in paradoxical sleep and a decrease in the light stages of slow wave sleep (SWS1), while 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), at a concentration selective for the non-NMDA receptors, produced a marked increase in SWS1. These results indicate a strong sleep-promoting action of excitatory amino acid antagonists and suggest that thalamic NMDA and non-NMDA receptors may play different roles in sleep regulation. Thus, changes in the sleep-waking cycle should be carefully evaluated when assessing the potential clinical use of excitatory amino acid antagonists.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1990

Pacemaker-like and other types of spontaneous membrane potential oscillations of thalamocortical cells.

During EEG-synchronized sleep, thalamic activity is characterized by rhythmic oscillations that till recently have been suggested to require the contribution of intra- and extra-thalamic inputs. The present experiments show that thalamocortical (TC) cells, mechanically and pharmacologically isolated from their intra-thalamic, cortical and brainstem inputs, are capable of different types of spontaneous membrane potential oscillations some of which resemble those observed in TC cells of the living animal during EEG-synchronization.

2-Amino-5-phosphonovalerate↗
PubMed1990

Postnatal development of the T calcium current in cat thalamocortical cells.

The burst firing of thalamic cells in the adult cat is mainly controlled by a voltage-dependent membrane current that has recently been characterized as being similar to the low voltage-activated (i.e. low threshold), T-type, Ca2+ current originally described in sensory neurons. In those neurons so far studied, as well as in skeletal muscle, the low threshold Ca2+ current has been shown to decrease in amplitude or even disappear during embryogenesis or the first few weeks of postnatal life. We have now investigated the in vivo postnatal development of the low threshold Ca2+ current present in thalamocortical cells of the dorsal lateral geniculate nucleus of cats aged four to 100 days. The results show that the amplitude of the low threshold Ca2+ current triples from 0.5 nA in the first few days after birth to over 1.5 nA in the adult. However, this increase in amplitude is not accompanied by any change in its inactivation and activation properties, its latency to peak and the time dependence of inactivation removal. Because of these similarities during development and in adulthood it is likely that a major role of the low threshold Ca2+ current during neuronal development is the generation of oscillatory activities similar to those observed in adult thalamocortical cells.

Animals↗
PubMed1989

Optic tract stimulation evokes GABAA but not GABAB IPSPs in the rat ventral lateral geniculate nucleus.

The inhibitory postsynaptic potentials (IPSPs) evoked in neurons of the rat ventral geniculate nucleus (vLGN) by electrical stimulation of the optic tract and the action of GABA and baclofen on the same cells were studied using intracellular recording technique in an in vitro slice preparation. A short latency short duration IPSP always followed the monosynaptic excitatory postsynaptic potential (EPSP). This IPSP reversed in polarity at about -65 mV and was reversibly blocked by bicuculline (50 microM) thus indicating that it represents a GABAA receptor-mediated IPSP. No long-lasting IPSP was evoked in vLGN cells by stimulation of the optic tract, while in the same slice, long-lasting GABAB IPSPs were routinely recorded in the dorsal lateral geniculate nucleus. GABA applied by ionophoresis evoked a hyperpolarization that had a reversal potential close to -70 mV and was antagonized by bicuculline. Baclofen hyperpolarized vLGN neurons and its action was reversibly blocked by the selective GABAB antagonist phaclofen (1 mM). In the presence of bicuculline GABA also produced a hyperpolarization that had properties similar to that evoked by baclofen. These results indicate that, although functional GABAA and GABAB receptors are present on vLGN neurons, stimulation of the optic tract evokes only GABAA but not GABAB mediated IPSPs. The lack of long-lasting GABAB IPSPs could explain the absence of long-lasting inhibition observed in vLGN neurons in vivo following stimulation of the optic tract.

Action Potentials↗
PubMed1989

On the properties and origin of the GABAB inhibitory postsynaptic potential recorded in morphologically identified projection cells of the cat dorsal lateral geniculate nucleus.

Intracellular recordings were performed from projection cells of the cat dorsal lateral geniculate nucleus in vitro to investigate the properties and origin of optic tract evoked inhibitory postsynaptic potentials mediated by GABAB receptors and their relationship to the physiologically different cell classes present in this nucleus. In all three main laminae of the dorsal lateral geniculate nucleus, stimulation of the optic tract evoked an excitatory postsynaptic potential followed by two inhibitory postsynaptic potentials. The first is a GABAA receptor mediated inhibitory postsynaptic potential since it was blocked by bicuculline, reversed in polarity following intracellular Cl- injection and had a reversal potential similar to the bicuculline sensitive hyperpolarizing effect of GABA. The second is a GABAB receptor mediated inhibitory postsynaptic potential. Its amplitude was not linearly related to membrane potential (maximal amplitude at -60 mV), it decreased when using frequencies of stimulation higher than 0.05 Hz and it was reversibly increased by addition of bicuculline to the perfusion medium. The reversal potential of GABAB inhibitory postsynaptic potentials was dependent on the extracellular K+ concentration but did not change in the presence of bicuculline or when recording with Cl- filled microelectrodes. While GABAA inhibitory postsynaptic potentials always abolished repetitive firing of projection cells, GABAB inhibitory postsynaptic potentials were able to block weak firing but unable to decrease strong activation of projection cells evoked by direct current injection. Optic tract evoked GABAB (as well as GABAA) inhibitory postsynaptic potentials could be recorded in slices which did not include the perigeniculate nucleus, thus indicating that they are generated by the interneurons of the dorsal lateral geniculate nucleus. Using intracellular injection of horseradish peroxidase, we have found that the GABAB inhibitory postsynaptic potentials are present in projection cells showing many different types of neuronal morphologies. In conclusion, GABA released from interneurons in the dorsal lateral geniculate nucleus is capable of evoking an early, short-lasting GABAA and a late, long-lasting GABAB inhibitory postsynaptic potential in projection cells with diverse morphology, indicating that the late inhibition in the dorsal lateral geniculate nucleus can no longer be associated exclusively with the recurrent inhibitory pathway through the perigeniculate nucleus.

Animals↗
PubMed1989

A T-type Ca2+ current underlies low-threshold Ca2+ potentials in cells of the cat and rat lateral geniculate nucleus.

1. The characteristics of a transient inward Ca2+ current (IT) underlying low-threshold Ca2+ potentials were studied in projection cells of the cat and rat dorsal lateral geniculate nucleus (LGN) in vitro using the single-electrode voltage-clamp technique. 2. In cat LGN slices perfused at 25 degrees C with a solution which included 1 mM-Ca2+ and 3 mM-Mg2+, IT could be evoked by depolarizing voltage steps to -55 mV from a holding potential (Vh) of -95 mV and was abolished by reducing [Ca2+]o from 1 to 0.1 mM. IT was also blocked by 8 mM-Mg2+ and 500 microM-Ni2+, but 500 microM-Cd2+ was a significantly less effective antagonist. 3. The inactivation of IT, which occurred at Vh positive to -65 mV, was removed as Vh approached -100 mV. The process of inactivation removal was also time dependent, with 800-1000 ms needed for total removal. Activation curves for IT showed a threshold of -70 mV and illustrated that IT was extremely voltage sensitive over the voltage range from -65 to -55 mV. 4. The decay phase of IT followed a single-exponential time course with a time constant of decay which was voltage sensitive and ranged from 20 to 100 ms. The mean peak conductance increase associated with IT was 8.4 nS (+/-0.9, S.E.M.). 5. In more 'physiological' conditions (35 degrees C and 1.5 mM-Ca2+, 1 mM-Mg2+) the voltage dependence of activation and inactivation were unaffected. However, the development and decay of IT proceeded more rapidly and only 500-600 ms were needed for total removal of inactivation. Under these conditions, the use of voltage ramps showed that depolarization rates of greater than 30 mV/s were necessary for IT activation. 6. The use of multiple voltage-step protocols illustrated that the process of inactivation removal was rapidly reversed by brief returns to a Vh of -50 mV. Furthermore, any delay in IT activation, once the LGN cell membrane potential was in the IT activation range, resulted in a current of reduced amplitude. 7. Although IT in rat LGN cells was briefer and had a shorter latency to peak, it was otherwise similar to that seen in cat LGN cells. 8. The characteristics of IT are very similar to those of the T-type Ca2+ currents of other excitable membranes. The properties of IT are discussed with respect to its role in generating the low-threshold Ca2+ potentials which are central to the oscillatory behaviour of thalamic projection cells.

Animals↗
PubMed1988

The GABAB antagonist phaclofen inhibits the late K+-dependent IPSP in cat and rat thalamic and hippocampal neurones.

Phaclofen (0.5-1 mM) reversibly inhibited the late, bicuculline resistant, K+ dependent IPSP recorded in projection cells of the cat and rat dorsal lateral geniculate nucleus and in rat hippocampal CA1 pyramidal neurones. At the same concentrations, phaclofen reversibly blocked the K+ dependent, bicuculline insensitive hyperpolarization evoked by GABA and baclofen but had no effect on the GABAA IPSP. These results represent conclusive evidence that GABAB receptors mediate the late K+ dependent IPSP in cortical and subcortical neurones.

Action Potentials↗
PubMed1988

Cl- - and K+-dependent inhibitory postsynaptic potentials evoked by interneurones of the rat lateral geniculate nucleus.

1. Hyperpolarizing potentials evoked by electrical stimulation of the optic tract were studied in projection cells of the rat dorsal lateral geniculate nucleus (LGN) in vitro. In the same cells the effects of gamma-amino butyric acid (GABA), baclofen and acetylcholine (ACh) were also investigated. 2. In the majority of cells a short- (SHP) (34 ms) and a long-lasting (LHP) (240 ms) hyperpolarizing potential could be recorded in the presence and in the absence of a preceding EPSP. They were blocked by tetrodotoxin (1 microM) and were more sensitive than the monosynaptic EPSP to a low-Ca2+-high-Mg2+ solution. 3. The SHP was associated with a marked decrease (75%) in input resistance, was blocked by bicuculline (1-100 microM) and its reversal potential (-67 mV) was dependent on the extracellular Cl- concentration. 4. The LHP was associated with a smaller decrease (45%) in input resistance and its reversal potential (-76 mV) was dependent on the extracellular K+ concentration. It was increased by bicuculline (100% at 50 microM) and nipecotic acid (30% at 10 microM), blocked by Ba2+ (1 mM), and unaffected by eserine (1-10 microM), neostigmine (1-10 microM) or by recording with EGTA-filled electrodes. In the presence of bicuculline, a single LHP was able to evoke, as a rebound response, a low-threshold Ca2+ spike that was, however, not followed by another LHP (or any other long-lasting hyperpolarization). 5. Ionophoretic applications of GABA evoked in the same cell a Cl- -dependent hyperpolarization (reversal potential: -65 mV) and/or depolarization, both of which were associated with a marked decrease (91%) in input resistance and abolished by bicuculline. GABA was also able to evoke a bicuculline-insensitive, K+-dependent hyperpolarization that had a reversal potential of -75 mV and was associated with a smaller decrease (43%) in input resistance. 6. Baclofen, applied by ionophoresis, pressure ejection or in the perfusion medium (1-100 microM), produced a hyperpolarization that had a reversal potential of -79 mV and was associated with a decrease (45%) in input resistance. 7. In the majority of cells (thirty-seven out of forty) ACh evoked a slow depolarization and only in three cells a hyperpolarization which had a reversal potential of -80 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1988

[Spontaneous rhythmic depolarization in the principal cells of the lateral geniculate body in vitro: the role of NMDA receptors].

Intracellular recordings using standard current clamp techniques were performed on projection cells of the rat lateral geniculate nucleus (LGN) in vitro. These cells are generally quiescent in vitro but when magnesium was removed from the perfusion medium they invariably showed rhythmic depolarizations (15-20 mV, 210-320 ms) that occurred at a frequency of 1.5-2 Hz and evoked 1 to 4 action potentials. This activity was completely blocked by micromolar concentrations of magnesium (50-150 microM) while tetrodotoxine (1 microM) abolished the action potentials but left the underlying rhythmic depolarizations unchanged. These results demonstrate that rat LGN projection cells are capable of producing rhythmic depolarizations in vitro and suggest the possibility that NMDA receptors might be involved in these rhythmic oscillations.

Action Potentials↗
PubMed1987

Neuroleptics decrease calcium-activated potassium conductance in hippocampal pyramidal cells.

Intracellular recordings were made from pyramidal CA1-neurones of the hippocampal slice preparation. Bath application of a wide variety of neuroleptics was found to depress the slow afterhyperpolarization, which is mediated in these neurons by a calcium-dependent potassium conductance occurring following a burst of spikes. The depression of this conductance took place in the presence of calcium spikes of normal amplitude and duration, and except in the case of trifluoperazine, without alteration in resting membrane potential or input resistance.

Animals↗
PubMed1987

An in vitro slice preparation of the cat lateral geniculate nucleus.

A slice preparation of the cat thalamus containing the lateral geniculate nucleus and the terminal portion of the optic tract is described. Ultrastructurally the slices remain relatively normal for only a short time after cutting. Indeed most cellular elements deteriorate quickly with time but patches of relatively intact tissue were still present even 10 h after cutting and maintenance in a storage bath. However, for 4-5 h after cutting long-lasting intracellular recordings of high quality and stability were obtained, and intrasomatic injection of horseradish peroxidase used for the morphological identification of recorded neurones as X or Y cells.

Animals↗