Depolarizing Postsynaptic Potential Research Articles

Основные нервные процессы – возбуждение и торможение как адаптивные реакции (обзор). Сообщение 1. Критический анализ эволюции теорий об основных нервных процессах и доказательство зависимости тормозного ответа нейронов от их текущего адаптационного состояния

In the work is criticized the paradigm about excitation and inhibition as the main nervous processes caused by the activity of specific excitatory and inhibitory systems. Analysis of the literature shows that the currently in neurophysiology dominant approach, justifying the existence of such systems, relies mainly on facts obtained in vitro, which are far from normal for the existence of nerve cells. Literature data are presented that indicate the dependence of the nature of the neuron response on its current adaptive (biological) state and the cytotoxicity of the neurotransmitter. In particular, in the review (part 1) it is shown that in response to the action of GABA (less toxic than neurotransmitter glutamate), brain neurons in both good (in vivo) and relatively bad (which is often in vitro) vital state will respond by hyperpolarizing postsynaptic potential (HPSP), either without excitation – the phenomenon of hyperpolarizational inhibition, or with the generation of nerve impulses, by posthyperpolarization recoil mechanism. In very poor living conditions (in vivo or in vitro), the neuronal response to GABA will always be a depolarizing postsynaptic potential (DPSP) with or without generation of action potentials (AP).

Coordinate high-frequency pattern of stimulation and calcium levels control the induction of LTP in striatal cholinergic interneurons

Current evidence appoints a central role to cholinergic interneurons in modulating striatal function. Recently, a long-term potentiation (LTP) of synaptic transmission has been reported to occur in these neurons. The relationship between the pattern of cortico/thalamostriatal fibers stimulation, the consequent changes in the intracellular calcium concentration ([Ca2+]i), and the induction of synaptic plasticity was investigated in striatal cholinergic interneurons from a rat corticostriatal slice preparation by means of combined electrophysiological intracellular recordings and microfluorometric techniques. Different protocols of stimulation were considered, varying both the frequency and the duration of the train of stimuli. High-frequency stimulation (HFS) (three trains at 100 Hz for 3 sec, 20-sec interval) induced a rise in [Ca2+]i, exceeding by fivefold the resting level, and caused a LTP of synaptic transmission. Tetanic stimulation delivered at lower frequencies (5-30 Hz) failed to induce long-term changes of synaptic efficacy. The observed elevation in [Ca2+]i during HFS was primarily mediated by L-type high-voltage activated (HVA)-Ca2+ channels, as it was fully prevented by nifedipine. Conversely, blockade of NMDA and AMPA glutamate receptor did not affect either LTP or the magnitude of the [Ca2+]i rise. Interestingly, the pharmacological analysis of the post-tetanic depolarizing postsynaptic potential (DPSP) revealed that LTP was attributable, to a large extent, to the potentiation of the GABA(A)-mediated component. In conclusion, the expression of LTP in striatal cholinergic interneurons is a selective response to a precise stimulation pattern of induction requiring a critical rise in [Ca2+]i.

Pemoline Alters Dopamine Modulation of Synaptic Responses of Neostriatal Neurons in vitro

Pemoline, a central stimulant, administered systemically at high doses (300 mg/kg) reliably produces self-biting behavior in rats. Pemoline-induced self-biting shares many similarities with self-injury seen in certain human disorders. Recent evidence has shown that alterations in neostriatal neurochemistry accompany the self-biting behavior seen in the rat. The present study used intracellular electrophysiological techniques to reveal changes in neostriatal cellular physiology in slices from rats which had displayed self-injury. Depolarizing postsynaptic potentials (DPSPs) were examined in neostriatal slices from rats that received pemoline and had been engaging in self-injurious behavior and from two control populations: rats that received the same concentration of pemoline and did not engage in self-biting, and rats that received vehicle alone (peanut oil). Data were acquired in standard artificial cerebral spinal fluid. DPSPs were evoked by cortical electrical stimulation in the slice. In neurons from rats that received the vehicle or that had received pemoline but had not engaged in self-injury, dopamine (DA, 20 microM) application produced a significant decrease in the size of the cortically evoked neostriatal DPSP. In contrast, DA application produced an increase in DPSP size in neurons from rats which had received pemoline and had engaged in self-injury. Bath application of a combination of D1 and D2 receptor agonists best replicated the enhancing effect of DA. Furthermore, the enhancement could be blocked by pretreatment with the competitive N-methyl-d-aspartate receptor antagonist, 2-amino-5-phosphonopentanoic acid. The results indicate that alterations in neostriatal DA-glutamate interactions accompany pemoline injections which produce self-injurious behavior.

Shunting of excitatory input to dentate gyrus granule cells by a depolarizing GABAA receptor-mediated postsynaptic conductance.

1. Stimulation of the perforant path in the outer molecular layer of the adult rat dentate gyrus produced a depolarizing post-synaptic potential (DPSP) in granule cells when recorded using whole-cell techniques in the standard hippocampal slice preparation at 34 degrees C. The postsynaptic currents (PSCs) contributing to the DPSP were analyzed using specific receptor antagonists in current- and voltage-clamp recordings. 2. The DPSP reversal potential was dependent on the intracellular chloride concentration, and the amplitude of the DPSP was increased 55% after perfusion of the gamma-aminobutyric acid-A (GABAA) receptor antagonist bicuculline methiodide (BMI). The GABAA receptor-mediated PSC reversed at -66 mV, which was 19 mV positive to the resting membrane potential (-85 mV) but hyperpolarized relative to action potential threshold. At -35 mV, the GABAA PSC had a latency to peak of 12.9 ms after the stimulus and decayed monoexponentially with an average time constant of 23.4 ms. 3. The component of the PSC blocked by the Quis/AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) had a latency to peak of 7.1 ms and decayed monoexponentially with a time constant of 9.9 ms at -35 mV. The N-methyl-D-aspartate (NMDA) receptor-mediated PSC, which was blocked by D-amino-5-phosphonovaleric acid (D-AP5), had a waveform that was similar to the GABAA PSC: the latency to peak was 16 ms and the decay was monoexponential with a time constant of 24.5 ms at -35 mV. 4. The ratio of the peak PSCs mediated by GABAA, Quis/AMPA, and NMDA receptors measured at -35 mV with cesium gluconate electrode solutions was 1:0.2:0.1. This ratio was essentially constant over the range of stimulus intensities that produced compound PSC amplitudes of 80-400 pA. 5. Measured at its reversal potential, the GABAA receptor-mediated postsynaptic conductance (GGABA-A) decreased the peak DPSP amplitude by 35%, shunted 50% of the charge transferred to the soma by the excitatory PSC, and completely inhibited the NMDA receptor-mediated component of the DPSP. 6. Simultaneous stimulation of presynaptic fibers from both the perforant path and interneurons results in a large depolarizing GGABA-A that inhibits the granule cell by shunting the excitatory PSCs. As predicted by models of shunting, the similar kinetics of the GABAA and NMDA PSCs leads to particularly effective inhibition of the NMDA PSC. The more rapid Quis/AMPA PSC is less affected by the GGABA-A, so that granule cell excitation under these conditions is primarily due to Quis/AMPA receptor activation.

Presynaptic dopamine D1 receptors attenuate excitatory and inhibitory limbic inputs to the shell region of the rat nucleus accumbens studied in vitro.

1. Intracellular recordings were made from the shell region of the nucleus accumbens in an in vitro slice preparation. The mean resting membrane potential, input resistance, and action potential amplitude of these neurons were -76 +/- 1 mV, 87 +/- 5 M omega and 94 +/- 2 mV (N = 108), respectively. A sample of these neurons (N = 18) was identified as medium spiny neurons with the use of the biocytin-avidin labeling technique. 2. Electrical stimulation of the fornix, subcortical fibers, or neuropil within the nucleus accumbens shell itself elicited a depolarizing postsynaptic potential (PSP). Dopamine (10-100 microM) attenuated PSPs elicited by stimulation of all of these sites. In a paired-pulse stimulation protocol, dopamine was observed to enhance the facilitation of the test response with respect to the conditioning response. 3. The suppressive effect of dopamine was mimicked by the D1 receptor agonist SKF 82958 (10-30 microM), whereas the D2 receptor agonist quinpirole (10-30 microM) was ineffective. The action of dopamine was antagonized by the D1 receptor antagonist Sch 23390 (10-30 microM), but not by the D2 receptor antagonist sulpiride (10-50 microM) or various adrenergic receptor antagonists. 4. The PSP was usually composed of an excitatory postsynaptic potential (EPSP)-inhibitory postsynaptic potential (IPSP) sequence. Dopamine equally attenuated the excitatory and inhibitory component of the synaptic response. The attenuation of both EPSP and IPSP did not depend on membrane potential. 5. Dopamine effects on the resting membrane potential and input resistance were variable and did not correlate with changes in the PSP. Two further indications were found in favor of a presynaptic locus of dopaminergic modulation. First, the time course of the PSP was not altered during dopamine application. Second, dopamine did not attenuate depolarizations induced by bath-applied L-glutamate. In extracellular recordings, it was found that dopamine reduced the population spike but not the presynaptic fiber volley. 6. These findings strongly indicate that dopaminergic modulation of synaptic responses in neurons located in the accumbens shell region is mediated by presynaptic D1 receptors. Notably, dopamine does not exert a purely inhibitory effect on synaptic excitability in the nucleus accumbens, because it suppresses both the excitatory and inhibitory component of the synaptic response.

Membrane properties and synaptic responses of rat striatal neurones in vitro.

1. A tissue slice containing a section of striatum was cut obliquely from rat brain so as to preserve adjacent cortex and pallidum. Intracellular recordings were made from 368 neurones, using either conventional or tight-seal configurations. 2. Two types of neurone were distinguished electrophysiologically. Principal cells (96%) had very negative resting potentials (-89 mV) and a low input resistance at the resting membrane potential (39 M omega): membrane conductance (10 nS at -65 mV) increased within tens of milliseconds after the onset of hyperpolarization (99 nS at -120 mV). Secondary cells (4%) had less negative resting potentials (-60 mV) and a higher input resistance (117 m omega at the resting potential): hyperpolarization caused an inward current to develop over hundreds of milliseconds that had the properties of H-current. 3. Most principal cells were activated antidromically by electrical stimulation of the globus pallidus or internal capsule. Intracellular labelling with biocytin showed that principal cells had a medium sized soma (10-18 microns), extensive dendritic trees densely studded with spines and, in some cases, a main axon which extended towards the globus pallidus. 4. Electrical stimulation of the corpus callosum or external capsule evoked a depolarizing postsynaptic potential. This synaptic potential was reversibly blocked by a combination of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) and DL-2-amino-5-phosphonovaleric acid (APV, 30 microM), but was unaffected by bicuculline (30 microM) and picrotoxin (100 microM). The underlying synaptic current had a fast component (time to peak about 4 ms), the amplitude of which was linearly related to membrane potential and which was blocked by CNQX; in CNQX the synaptic current had a slower component (time to peak about 10 ms) which showed voltage dependence typical of N-methyl-D-aspartate (NMDA) receptors. Both currents reversed at -5 mV. 5. Focal electrical stimulation within the striatum (100-300 microns from the site of intracellular recording) evoked a synaptic potential that was partially blocked (45-95%) by CNQX and APV: the remaining synaptic potential was blocked by bicuculline (30 microM). The bicuculline-sensitive synaptic current reversed at the chloride equilibrium potential. 6. The findings confirm that the majority of neostriatal neurones (principal cells, medium spiny neurones) project to the pallidum and receive synaptic inputs from cerebral cortex mediated by an excitatory amino acid acting through NMDA and non-NMDA receptors. These cells also receive synaptic inputs from intrinsic striatal neurones mediated by GABA.(ABSTRACT TRUNCATED AT 400 WORDS)

Hippocampal inputs to identified neurons in an in vitro slice preparation of the rat nucleus accumbens: evidence for feed-forward inhibition

The aim of the present study was to analyze responses of nucleus accumbens neurons to stimulation of the fornix. The recorded neurons were labeled with biocytin and identified as medium spiny neurons. A large majority of cells generated a depolarizing postsynaptic potential in response to stimulation of the fornix. Using intracellular current injection, this depolarizing response was dissociated into an EPSP reversing at -6 +/- 6 mV and an IPSP reversing at -71 +/- 4 mV. Both the EPSP and IPSP were abolished by 6-cyano-7-nitroquinoxaline-2,3-dione. In addition, the IPSP was blocked by bicuculline and picrotoxin. The onset latency of the EPSP was constant in spite of varying stimulus intensities. In contrast, the onset latency of the IPSP increased with decreasing stimulus intensity. Notably, the stimulus threshold for evoking IPSPs was generally lower than for EPSPs. At stimulus intensities well above threshold, the IPSP onset was only slightly delayed with respect to the EPSP onset. These results indicate that the EPSP can be characterized as a monosynaptic and glutamate-mediated synaptic response. The IPSP, however, appears to be mediated by a disynaptic feed-forward pathway involving both glutamate and GABAA receptors. Recurrent and lateral inhibitory interactions have previously been proposed to be predominant organizational principles in the caudate-putamen and nucleus accumbens. This study indicates that feed-forward inhibition is an additional principle governing the activities of striatal neural networks.

Involvement of GABA systems in feedback regulation of glutamate-and GABA-mediated synaptic potentials in rat neostriatum.

1. Neostriatal neurones were recorded intracellularly from a rat corticostriatal slice preparation. Depolarizing postsynaptic potentials (DPSPs) were evoked by either cortical or intrastriatal stimulation. 2. Kynurenic acid (600 microM), an antagonist of excitatory amino acids, reduced the cortically-evoked DPSPs by 88% while the intrastriatally evoked potentials were reduced by 48%. Bicuculline (100 microM) produced only a slight inhibition of the cortically evoked DPSPs (12%), but clearly depressed intrastriatal potentials (52%). 3. The effects of (-)-baclofen, a gamma-aminobutyric acid (GABA)B receptor agonist, were studied on the cortically evoked DPSPs. In all the tested neurones (-)-baclofen, added to the superfusion medium, caused a concentration-dependent decrease of these potentials (half-maximal effect (EC50) = 800 nM). This effect was not affected by bicuculline. (-)-Baclofen did not change the membrane potential, the input resistance, current-evoked firing frequency, or postsynaptic responses to exogenously applied glutamate. 4. The effects of (-)-baclofen on the DPSPs were compared to those produced by application of GABA and muscimol. GABA and muscimol decreased the DPSPs and caused a membrane depolarization coupled with a decrease of the membrane resistance. Bicuculline (100 microM) blocked the GABA-induced changes of the membrane potential and of the resistance, but not the decrease of the synaptic potentials. All the effects produced by muscimol were blocked by bicuculline. 5. Following intrastriatal stimulation a residual kynurenate-insensitive potential persisted; this potential was blocked by bicuculline (100 microM). (-)-Baclofen produced a dose-dependent decrease of this potential (EC50 = 800 nM). The postsynaptic responses to exogenously applied GABA were unchanged by (-)-baclofen. 6. The amplitude of kynurenate and bicuculline-sensitive DPSPs were stable at a frequency of 0.1 Hz. At frequencies between 0.3 and 3 Hz both these potentials were attenuated with the second stimulus and after about five stimuli a steady state was reached. Membrane potential and input resistance were not affected by these frequencies of stimulation. 7. Application of the GABA uptake inhibitor nipecotic acid (100-300 microM) clearly reduced the amplitude of both kynurenate-and bicuculline-sensitive DPSPs evoked at low frequencies of stimulation (0.01-0.3 Hz), but had lower effects at higher stimulation rates (1-3 Hz). Application of nipecotic acid increased the duration of membrane responses to exogenously applied GABA.(ABSTRACT TRUNCATED AT 400 WORDS)

Contribution of NMDA receptors to postsynaptic potentials and paired-pulse facilitation in identified neurons of the rat nucleus accumbens in vitro

The principal aim of this study was to characterize the transmitter mechanisms mediating fast postsynaptic potentials in identified neurons of the rat nucleus accumbens. Using the biocytin-avidin labeling technique, impaled neurons were identified as medium spiny neurons. The basic membrane characteristics of these neurons were determined. Local electrical stimulation or stimulation of the corpus callosum elicited a depolarizing postsynaptic potential consisting of an EPSP often followed by an IPSP. The quisqualate/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (4 microM) abolished most of the depolarizing postsynaptic potential. The N-methyl-D-aspartate receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid depressed a small part of the decay phase of the depolarizing postsynaptic potential. Paired-pulse facilitation of postsynaptic potentials was found using interstimulus-intervals between 10 and 150 ms. N-methyl-D-aspartate receptors were found to contribute only slightly to the facilitation of the decay phase of the depolarizing postsynaptic potential, but not to its rising phase. This contribution was particularly clear under conditions of reduced GABAA receptor mediated inhibition. The present study indicates that postsynaptic responses of medium spiny neurons in the nucleus accumbens to local stimulation or stimulation of neocortical afferents are primarily mediated by quisqualate/kainate receptors. The contribution of NMDA receptors is normally limited to a portion of the decay phase of these responses, but is enlarged in the absence of GABAergic inhibition and following paired-pulse stimulation.

Intracellular recordings from rat nucleus accumbens neurons in vitro

Intracellular recordings were obtained from rat nucleus accumbens (NAC) neurons in brain slice preparations. Local stimulations evoked depolarizing postsynaptic potential (DPSP). Injections of low density depolarizing currents decreased the amplitude of the DPSP and reversed a later portion of the DPSP into a hyperpolarizing potential. Superfusion of pentobarbital facilitated the reversal of this later portion of DPSP and bicuculline abolished this polarity reversal. These data suggested that the DPSP evoked by local stimulation consisted of a combination of an excitatory and an inhibitory postsynaptic potential, and that the latter was probably mediated by γ-aminobutyric acid.

Local stimulation induced GABAergic response in rat striatal slice preparations: Intracellular recordings on QX-314 injected neurons

Gamma-aminobutyric acid (GABA)ergic responses evoked by electrical stimulation in the neostriatal slice preparation were studied in neurons injected intracellularly with Na-conductance blocker QX-314. Local stimulation elicited depolarizing postsynaptic potentials (DPSPs) in the QX-314-injected neurons when the membrane potential was morenegative than −60 mV. When DPSPs were minimized by depolirizing current injection in the QX-314-injected neuron, hyperpolarization was clearly observed following local stimulation. The maximum duration of the hyperpolarizing response to strong local stimulation was about 130 ms. The hyperpolarizing response was blocked by the addition of bicuculine or picrotoxin to the Ringer solution. Intracellular Cl - injections produced changes in the pattern of the local stimulations-induced responses; the initial depolarizing response was followed by a relatively large amplitude long duration depolarization. The polarity of the long duration of depolarizing response could not be reversed by depolarizing currents which were normally sufficient to reverse the polarity of DPSPs in the neurons without Cl - injection. The application of pentobarbital enhanced the amplitude and the duration of the hyperpolarizing responses. The revealed potential of the pentobarbital-enhanced response was estimated to be −60 mV. On the basis of their reversal potential, sensitivity to injected Cl -, sensitivity to GABA blockers picrotoxin and bicuculine, and the effect of pentobarbital, these hyperpolarizing responses are shown to be GABAergic Cl - mediated inhibitory postsynaptic potentials (IPSPs).

Active membrane properties of rat neostriatal neurons in an in vitro slice preparation.

The active membrane properties of rat neostriatal neurons have been studied in an in vitro slice preparation. All the neurons examined had resting membrane potentials of more than 50 mV and generated action potentials with amplitudes exceeding 70 mV. The morphological characteristics of the neurons identified by intracellular labeling with HRP indicated that they were medium spiny neurons. Depolarizing current injection through the recording microelectrode generated slow depolarizing potentials and repetitive action potentials with frequencies ranging from less than 10 Hz to over 300 Hz. Adaptation of action potentials was observed when long duration depolarizing current was injected. Depolarizing current injections revealed that the membrane of the striatal neuron had an anomalous rectification when the membrane potential was depolarized to the resting potential. A possible bases for the anomalous rectification might involve inactivation of K-conductance and slow inward Ca- and/or Na-currents. Local electrical stimulation evoked depolarizing postsynaptic potentials (DPSPs) followed by long-lasting small depolarizations. In a double stimulation test, a potentiation of the test DPSP was observed at interstimulus time interval of up to 80 ms. Post-tetanic potentiation of DPSPs was also seen in these neurons. Tests utilizing depolarizing current injection, intracellular Cl- injection, and Cl-conductance blocking drugs indicated that the DPSPs were composed of EPSPs and overlapping IPSPs. The nature of the long-lasting small depolarization succeeding the DPSPs could not be conclusively determined. However, available data suggest that the slow inward Ca-current may be responsible for this response.(ABSTRACT TRUNCATED AT 250 WORDS)