Synaptic and intrinsic control of membrane excitability of neostriatal neurons. I. An in vivo analysis

1990 ◽  
Vol 63 (4) ◽  
pp. 651-662 ◽  
Author(s):  
P. Calabresi ◽  
N. B. Mercuri ◽  
A. Stefani ◽  
G. Bernardi

1. The relationship between membrane properties of neostriatal neurons and spontaneous and evoked synaptic potentials was studied with the use of intracellular recordings from anesthetized rats. Most of these neurons showed regular or irregular spontaneous depolarizing potentials that only in a few cases triggered action potentials at resting level. 2. The stimulation of the ipsilateral substantia nigra or of the sensorimotor cortex produced a relatively fast depolarizing post-synaptic potential (EPSP). In some cells this potential was followed by an inhibitory period that appeared as an hyperpolarization when the cell was depolarized from the resting level (inhibitory postsynaptic potential, IPSP). A late and long-lasting depolarization (LD) followed the EPSP or the EPSP-IPSP sequence. 3. Repetitive discharge with little adaptation was observed during direct depolarization. Most of the neurons tested for current-voltage (I-V) relationship showed nonlinearity of the input resistance in the hyperpolarizing direction. Spontaneous and evoked EPSPs were decreased in their amplitude and duration when the membrane potential was held at levels more hyperpolarized than -85 mV because of the strong rectification at these levels of hyperpolarization. 4. Local microiontophoretic application of bicuculline (BIC) or systemic administration of BIC and pentylenetetrazole (PTZ) produced a reduction of the IPSPs. The reduction of the inhibitory transmission caused a strong increase of the LD. The current-evoked firing pattern was not greatly altered. 5. The intracellular application of cesium increased the amplitude and the duration of the spontaneous depolarizations that triggered bursts of action potentials under this condition. Spikes were broadened and the rectification in the hyperpolarization direction was reduced. 6. Iontophoretically applied cadmium strongly depressed the amplitude of the spontaneous and evoked postsynaptic potentials. During cadmium application, nigral stimulation produced constant latency, all-or-none spikes in the absence of any synaptic potential. 7. Repetitive stimulation of the ipsilateral substantia nigra by electrical shocks (5 Hz, 25 s) produced a progressive and reversible decrease of the spontaneous depolarizing potentials (SDPs) and a decrease of the firing rate. In the same cells, when the train of stimulation was delivered in the ipsilateral cortex, a membrane depolarization coupled with an increase of the firing rate was observed. 8. We conclude that although synaptic circuits mediate a phasic inhibition in neostriatum, the low level of spontaneous firing of most neostriatal neurons is mainly because of the effects that membrane properties exert on the spontaneous and the evoked synaptic depolarizations in the striatum.(ABSTRACT TRUNCATED AT 400 WORDS)

2000 ◽  
Vol 83 (4) ◽  
pp. 1796-1808 ◽  
Author(s):  
Anthony R. West ◽  
Anthony A. Grace

A major component of the cortical regulation of the nigrostriatal dopamine (DA) system is known to occur via activation of striatal efferent systems projecting to the substantia nigra. The potential intermediary role of striatal nitric oxide synthase (NOS)-containing interneurons in modulating the efferent regulation of DA neuron activity was examined using single-unit recordings of DA neurons performed concurrently with striatal microdialysis in anesthetized rats. The response of DA neurons recorded in the substantia nigra to intrastriatal artificial cerebrospinal fluid (ACSF) or drug infusion was examined in terms of mean firing rate, percent of spikes fired in bursts, cells/track, and response to electrical stimulation of the orbital prefrontal cortex (oPFC) and striatum. Intrastriatal infusion of NOS substrate concurrently with intermittent periods of striatal and cortical stimulation increased the mean DA cell population firing rate as compared with ACSF controls. This effect was reproduced via intrastriatal infusion of a NO generator. Infusion of either a NOS inhibitor or NO chelator via reverse microdialysis did not affect basal firing rate but increased the percentage of DA neurons responding to striatal stimulation with an initial inhibition followed by a rebound excitation (IE response) from 40 to 74%. NO scavenger infusion also markedly decreased the stimulation intensity required to elicit an IE response to electrical stimulation of the striatum. In single neurons in which the effects of electrical stimulation were observed before and after drug delivery, NO antagonist infusion was observed to decrease the onset latency and extend the duration of the initial inhibitory phase induced by either oPFC or striatal stimulation. This is the first report showing that striatal NO tone regulates the basal activity and responsiveness of DA neurons to cortical and striatal inputs. These studies also indicate that striatal NO signaling may play an important role in the integration of information transmitted to basal ganglia output centers via corticostriatal and striatal efferent pathways.


1985 ◽  
Vol 54 (2) ◽  
pp. 245-260 ◽  
Author(s):  
C. E. Stansfeld ◽  
D. I. Wallis

The active and passive membrane properties of rabbit nodose ganglion cells and their responsiveness to depolarizing agents have been examined in vitro. Neurons with an axonal conduction velocity of less than 3 m/s were classified as C-cells and the remainder as A-cells. Mean axonal conduction velocities of A- and C-cells were 16.4 m/s and 0.99 m/s, respectively. A-cells had action potentials of brief duration (1.16 ms), high rate of rise (385 V/s), an overshoot of 23 mV, and relatively high spike following frequency (SFF). C-cells typically had action potentials with a "humped" configuration (duration 2.51 ms), lower rate of rise (255 V/s), an overshoot of 28.6 mV, an after potential of longer duration than A-cells, and relatively low SFF. Eight of 15 A-cells whose axons conducted at less than 10 m/s had action potentials of longer duration with a humped configuration; these were termed Ah-cells. They formed about 10% of cells whose axons conducted above 2.5 m/s. The soma action potential of A-cells was blocked by tetrodotoxin (TTX), but that of 6/11 C-cells was unaffected by TTX. Typically, A-cells showed strong delayed (outward) rectification on passage of depolarizing current through the soma membrane and time-dependent (inward) rectification on inward current passage. Input resistance was thus highly sensitive to membrane potential close to rest. In C-cells, delayed rectification was not marked, and slight time-dependent rectification occurred in only 3 of 25 cells; I/V curves were normally linear over the range: resting potential to 40 mV more negative. Data on Ah-cells were incomplete, but in our sample of eight cells time-dependent rectification was absent or mild. C-cells had a higher input resistance and a higher neuronal capacitance than A-cells. In a proportion of A-cells, RN was low at resting potential (5 M omega) but increased as the membrane was hyperpolarized by a few millivolts. A-cells were depolarized by GABA but were normally unaffected by 5-HT or DMPP. C-cells were depolarized by GABA in a similar manner to A-cells but also responded strongly to 5-HT; 53/66 gave a depolarizing response, and 3/66, a hyperpolarizing response. Of C-cells, 75% gave a depolarizing response to DMPP.(ABSTRACT TRUNCATED AT 400 WORDS)


1990 ◽  
Vol 63 (3) ◽  
pp. 502-522 ◽  
Author(s):  
R. Lal ◽  
M. J. Friedlander

1. Extracellular recordings were made from single neurons in layer A of the left dorsal lateral geniculate nucleus (LGNd) of anesthetized and paralyzed adult cats. Responses to retinotopically identical visual stimuli (presented through the right eye) were recorded at several positions of the left eye in its orbit. Visual stimuli consisted of drifting sinusoidal gratings of optimal temporal and spatial frequencies at twice threshold contrast. Visual stimulation of the left eye was blocked by a variety of methods, including intravitreal injection of tetrodotoxin (TTX). The change in position of the left eye was achieved by passive movements in a randomized and interleaved fashion. Of 237 neurons studied, responses were obtained from 143 neurons on 20-100 trials of identical visual stimulation at each of six eye positions. Neurons were classified as X- or Y- on the basis of a standard battery of physiological tests (primarily linearity of spatial summation and response latency to electrical stimulation of the optic chiasm). 2. The effect of eye position on the visual response of the 143 neurons was analyzed with respect to the number of action potentials elicited and the peak firing rate. Fifty-seven (40%) neurons had a significant effect [by one-factor repeated-measure analysis of variance (ANOVA), P less than 0.05] of eye position on the visual response by either criterion (number of action potentials or peak firing rate). Of these 57 neurons, 47 had a significant effect (P less than 0.05) with respect to the number of action potentials and 23 had a significant effect (P less than 0.05) by both criteria. Thus the permissive measure by either criterion and the conservative measure by both criteria resulted in 40% and 16%, respectively, of all neurons' visual responses being significantly affected by eye position. 3. For the 47 neurons with a significant effect of eye position (number of action potentials criterion), a trend analysis of eye position versus visual response showed a linear trend (P less than 0.05) for 9 neurons, a quadratic trend (P less than 0.05) for 32 neurons, and no significant trend for the 6 remaining neurons. The trends were approximated with linear and nonlinear gain fields (range of eye position change over which the visual response was modulated). The gain fields of individual neurons were compared by measuring the normalized gain (change in neuronal response per degree change of eye position). The mean normalized gain for the 47 neurons was 4.3. 4. The nonlinear gain fields were generally symmetric with respect to nasal versus temporal changes in eye position.(ABSTRACT TRUNCATED AT 400 WORDS)


1999 ◽  
Vol 16 (3) ◽  
pp. 557-570 ◽  
Author(s):  
HONGJING TAN ◽  
RICHARD D. MOONEY ◽  
ROBERT W. RHOADES

Intracellular recording techniques were used to evaluate the effects of norepinephrine (NE) on the membrane properties of superficial layer (stratum griseum superficiale and stratum opticum) superior colliculus (SC) cells. Of the 207 cells tested, 44.4% (N = 92) were hyperpolarized by ≥3 mV and 8.7% (N = 18) were depolarized by ≥3 mV by application of NE. Hyperpolarization induced by NE was dose dependent (EC50 = 8.1 μM) and was associated with decreased input resistance and outward current which had a reversal potential of −94.0 mV. Depolarization was associated with a very slight rise in input resistance and had a reversal potential of −93.1 mV for the single cell tested. Pharmacologic experiments demonstrated that isoproterenol, dobutamine, and p-aminoclonidine all hyperpolarized SC cells. These results are consistent with the conclusion that NE-induced hyperpolarization of SC cells is mediated by both α2 and β1 adrenoceptors. The α1 adrenoceptor agonists, methoxamine and phenylephrine, depolarized 35% (6 of 17) of the SC cells tested by ≥3 mV. Most of the SC cells tested exhibited responses indicative of expression of more than one adrenoceptor. Application of p-aminoclonidine or dobutamine inhibited transsynaptic responses in SC cells evoked by electrical stimulation of optic tract axons. Inhibition of evoked responses by these agents was usually, but not invariably, associated with a hyperpolarization of the cell membrane and a reduction in depolarizing potentials evoked by application of glutamate. The present in vitro results are consistent with those of the companion in vivo study which suggested that NE-induced response suppression in superficial layer SC neurons was primarily postsynaptic and chiefly mediated by both α2 and β1 adrenoceptors.


1990 ◽  
Vol 259 (6) ◽  
pp. L403-L409 ◽  
Author(s):  
A. C. Myers ◽  
B. J. Undem ◽  
D. Weinreich

Active and passive membrane membrane properties of parasympathetic neurons were examined in vitro in a newly localized ganglion on the right bronchus of the guinea pig. Neurons could be classified as “tonic” or “phasic” based on their action potential discharge response to suprathreshold depolarizing constant current steps. Tonic neurons (39%) responded with repetitive action potentials sustained throughout the current step, whereas phasic neurons (61%) responded with an initial burst of action potentials at the onset of the step but then accommodated. Tonic and phasic neurons could not be differentiated by other active or passive membrane properties. Electrical stimulation of the vagus nerve elicited one to three temporally distinct fast nicotinic excitatory potentials, and tetanic stimulation of the vagus nerve evoked slow depolarizing (10% of neurons) and hyperpolarizing (25% of neurons) potentials; the latter was mimicked by muscarinic receptor activation. Similar slow and fast postsynaptic potentials were observed in both tonic and phasic neurons. We suggest neurons within the bronchial ganglion possess membrane and synaptic properties capable of integrating presynaptic stimuli.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Daniel J Galtieri ◽  
Chad M Estep ◽  
David L Wokosin ◽  
Stephen Traynelis ◽  
D James Surmeier

Burst spiking in substantia nigra pars compacta (SNc) dopaminergic neurons is a key signaling event in the circuitry controlling goal-directed behavior. It is widely believed that this spiking mode depends upon an interaction between synaptic activation of N-methyl-D-aspartate receptors (NMDARs) and intrinsic oscillatory mechanisms. However, the role of specific neural networks in burst generation has not been defined. To begin filling this gap, SNc glutamatergic synapses arising from pedunculopotine nucleus (PPN) neurons were characterized using optical and electrophysiological approaches. These synapses were localized exclusively on the soma and proximal dendrites, placing them in a good location to influence spike generation. Indeed, optogenetic stimulation of PPN axons reliably evoked spiking in SNc dopaminergic neurons. Moreover, burst stimulation of PPN axons was faithfully followed, even in the presence of NMDAR antagonists. Thus, PPN-evoked burst spiking of SNc dopaminergic neurons in vivo may not only be extrinsically triggered, but extrinsically patterned as well.


2005 ◽  
Vol 94 (4) ◽  
pp. 2805-2821 ◽  
Author(s):  
Michael Rudolph ◽  
Joe Guillaume Pelletier ◽  
Denis Paré ◽  
Alain Destexhe

The activation of the electroencephalogram (EEG) is paralleled with an increase in the firing rate of cortical neurons, but little is known concerning the conductance state of their membrane and its impact on their integrative properties. Here, we combined in vivo intracellular recordings with computational models to investigate EEG-activated states induced by stimulation of the brain stem ascending arousal system. Electrical stimulation of the pedonculopontine tegmental (PPT) nucleus produced long-lasting (≈20 s) periods of desynchronized EEG activity similar to the EEG of awake animals. Intracellularly, PPT stimulation locked the membrane into a depolarized state, similar to the up-states seen during deep anesthesia. During these EEG-activated states, however, the input resistance was higher than that during up-states. Conductance measurements were performed using different methods, which all indicate that EEG-activated states were associated with a synaptic activity dominated by inhibitory conductances. These results were confirmed by computational models of reconstructed pyramidal neurons constrained by the corresponding intracellular recordings. These models indicate that, during EEG-activated states, neocortical neurons are in a high-conductance state consistent with a stochastic integrative mode. The amplitude and timing of somatic excitatory postsynaptic potentials were nearly independent of the position of the synapses in dendrites, suggesting that EEG-activated states are compatible with coding paradigms involving the precise timing of synaptic events.


1991 ◽  
Vol 157 (1) ◽  
pp. 101-122
Author(s):  
WERNER A. WUTTKE ◽  
MICHAEL S. BERRY

1. The giant salivary cells of Haementeria ghilianii are known to produce Ca2+-dependent action potentials and to release their secretory products in response to stimulation of the stomatogastric nerve. In this study, the electrophysiological effects of some putative transmitters were examined by perfusion of the gland and two promising candidates were selected for detailed analysis. 2. Acetylcholine (ACh) was the only substance tested which excited the gland cells. It produced a large, Na+-dependent depolarization that elicited 1–3 action potentials and desensitized to about 24% of its maximal value within 2 min. 3. Carbachol, tetramethylammonium and nicotine elicited similar responses to ACh, whereas choline and pilocarpine had negligible effects. 4. The ACh response was completely blocked by d-tubocurarine and strychnine, and was reduced by tetraethylammonium, hexamethonium and atropine. The receptors, therefore, cannot be clearly distinguished as nicotinic or muscarinic. 5. ACh did not elicit secretion, but this does not necessarily preclude it from acting as a neuroglandular transmitter. 6. 5-Hydroxytryptamine (5-HT) was the only transmitter candidate that elicited secretion, though it did not excite the gland cells. 7. 5-HT produced a subthreshold depolarization and an increase in input resistance. Action potentials, elicited by depolarizing pulses, were increased in amplitude and duration, and showed greatly reduced adaptation. 8. 5-HT potentiated the net inward current, evoked by subthreshold depolarizing pulses, by reducing outward K+ current. The inward current, carried by Ca2+, was not directly affected. In addition, 5-HT increased an inwardly rectifying current, carried by Na+ and K+. All the effects of 5-HT tended to increase cell excitability. 9. Salivary cell responses to 5-HT were reversibly antagonised by methysergide. 10. Responses to ACh or 5-HT were not mimicked by 3′, 5′-cyclic guanosine monophosphate, which greatly reduced spike amplitude and excitability. The effects were specific to the 3′, 5′ form; 2′, 3′-cyclic GMP had no effect. Cyclic GMP dramatically reduced the duration of action potentials that had been artificially prolonged by TEA+ or removal of external Ca2+. 11. Cyclic 3′, 5′-adenosine monophosphate and its dibutyryl derivative had little effect on membrane properties. 8-Bromo-cyclic AMP, however, mimicked all the effects of 5-HT. It is thought that 5-HT may exert its actions via cyclic AMP. 12. The possible role of 5-HT in salivary secretion is discussed.


2001 ◽  
Vol 85 (5) ◽  
pp. 1986-1997 ◽  
Author(s):  
Natas̆a Savić ◽  
Paola Pedarzani ◽  
Marina Sciancalepore

Stratum (st.) radiatum interneurons represent a heterogeneous class of hippocampal cells with as yet poorly characterized physiological properties. Intracellular staining with biocytin, in situ hybridization, and patch-clamp recording have been combined to investigate the morphological and electrophysiological properties of these cells in the CA3 hippocampal region in young rats [ postnatal days 10 to 21 ( P10–21)]. Labeled cells presented a heterogeneous morphology with various soma shapes, often found multipolar, and dendritic arborizations confined to st. radiatum. The passive membrane properties of these st. radiatum interneurons showed instead no significant differences between P10 and P21. Low resting potential, high-input resistance, and short time constants characterized CA3 st. radiatum interneurons, which were silent at rest. Action potentials, elicited by brief current pulses, were lower and shorter than in pyramidal cells and followed by a Ca2+-dependent medium-duration afterhyperpolarizing potential (mAHP). Prolonged depolarizing current injection generated trains of action potentials that fired at constant frequency after a slight accommodation. The maximum steady-state firing rate was 31 ± 4 (SD) Hz. Hyperpolarizing current pulses revealed a prominent inward rectification characterized by a “sag,” followed by a depolarizing rebound that triggered action potentials. Sag and anodal brake excitation were blocked by Cs+, suggesting that they were mediated by a hyperpolarization-activated cation conductance ( I h). In the presence of tetrodotoxin and tetraethylammonium, biphasic tail currents were elicited in voltage clamp after a depolarizing step inducing Ca2+influx. Tail currents presented a fast Ca2+-activated and apamin-sensitive component ( I AHP) and were further reduced by carbachol. The presence of I AHP was consistent with the high expression level of the apamin-sensitive SK2 subunit transcript in CA3 st. radiatum interneurons as detected by in situ hybridization. Different pharmacological agents were shown to affect the afterhyperpolarizing potential as well as the firing properties of st. radiatum interneurons. Exposure to Ca2+-free solutions mainly affected the late phase of repolarization and strongly reduced the mAHP. The mAHP was also attenuated by carbachol and by apamin, suggesting it to be partly mediated by I AHP. Reduction of the mAHP increased the interneuron firing frequency. In conclusion, st. radiatum interneurons of CA3 hippocampal region represent a class of nonpyramidal cells with action potentials followed by an AHP of relatively short duration, partially generated by apamin and carbachol-sensitive conductances involved in the regulation of the cell firing rate.


Sign in / Sign up

Export Citation Format

Share Document