Norepinephrine decreases synaptic inhibition in the rat hippocampus

The effects of norepinephrine (NE) on inhibitory synaptic potentials were studied on CA1 pyramidal neurons in the hippocampal slice in vitro. Norepinephrine caused the appearance of multiple population spikes in the CA1 region of the hippocampal slice, reminiscent of the actions of gamma-aminobutyric acid (GABA) antagonists. Intracellular recording revealed that NE causes a marked and reversible reduction in inhibitory postsynaptic potentials (IPSPs) recorded in CA1 pyramidal cells. This reduced IPSP results in a larger intracellular excitatory postsynaptic potential (EPSP), which can cause the cell to fire more than one action potential. This disinhibitory effect of NE appears to be mediated by an alpha-receptor, and occurs at a site presynaptic to the pyramidal cell, since NE does not change the reversal potential of the IPSP nor does it affect the amplitude or the reversal potential of iontophoretic GABA responses. In addition to reducing evoked IPSPs, NE causes an increase in the frequency of spontaneous IPSPs, suggesting that inhibition of interneuronal firing may not account for this disinhibitory action of NE.     

Conductance changes and inhibitory actions of hippocampal recurrent IPSPs

Intracellular recordings were obtained from CA1 pyramidal neurons in obliquely cut in vitro hippocampal slices. Recurrent IPSPs were elicited by antidromic stimulation of alvear fibers. The mechanisms by which IPSPs depress pyramidal cell excitability were investigated.Recurrent IPSPs could be reversed in sign by small hyperpolarizing currents applied through the recording electrode, indicating an increased membrane conductance. By using an AC bridge circuit it was found that the maximum impedance decrease usually occurred slightly before the peak of the IPSP. Otherwise the time course of the impedance change matched that of the IPSP itself.Inhibitory actions of the conductance increase were studied by adjusting the membrane potential to the IPSP equilibrium potential, thus allowing only the IPSP conductance to play an inhibitory role. Under these conditions non-linear summation of recurrent IPSPs with EPSPs originating in the apical dendrites could be demonstrated only during the initial 15–25 msec of the IPSP, which is the period of maximum conductance increase.The inhibition afforded by the hyperpolarization of the recurrent IPSP far outlasts the period of effective EPSP shunting by the inhibitory synaptic currents. The mechanisms of recurrent inhibition in the hippocampus thus appear similar to those operating in spinal motoneuron IPSPs.     

Properties of stereotyped series of postsynaptic potentials in hypoglossal motoneurons

A stereotyped series of postsynaptic potentials produced in cat hypoglossal motoneurons by stimulation of the cerebral cortex, the inferior alveolar nerve or the lingual nerve was studied. These include an excitatory postsynaptic potentials (EPSP) and subsequently 3 different types of inhibitory postsynaptic potential (IPSPs). The first is a short-lasting IPSP which was blocked by strychnine administration. The second is a γ-aminobutyric acid (GABA) IPSP which was blocked by picrotoxin administration. This IPSP was sensitive to membrane polarization and dependent on a conductance increase. The third is a long-duration hyperpolarizing potential which was enhanced by the injection of picrotoxin and insensitive to membrane polarization. Moreover, we have demonstrated that the amplitude of cortically induced EPSPs decreased greatly with depolarization.     

Bicuculline- and Phaclofen-Resistant Hyperpolarizations Evoked by Glutamate Applications to Stratum Lacunosum-Moleculare in CA1 Pyramidal Cells of the Rat Hippocampus In Vitro

In the hippocampus, different types of interneurons may mediate distinct gamma-aminobutyric acid (GABA) responses, i.e. the early and late inhibitory postsynaptic potentials (IPSPs). To verify this hypothesis, intracellular recordings were obtained from CA1 pyramidal cells (n=63) in rat hippocampal slices. Glutamate (1 mM) was locally ejected in stratum lacunosum-moleculare to activate interneurons in this region. Glutamate-evoked hyperpolarizing responses were characterized in pyramidal cells and compared to the early IPSP and the late IPSP elicited by stratum radiatum electrical stimulation. Several characteristics were similar for the glutamate-evoked IPSPs and late IPSPs: their amplitude was small (-3.4 versus -4.9 mV, respectively), each was associated with a small conductance increase (5.0 versus 9.3 nS, respectively), their peak latency was slow (124.4 versus 129.8 ms, respectively) and in the majority of cells, each displayed little response reversal. However, the equilibrium potential of the glutamate IPSP (-76.5 mV) was similar to that of the early IPSP (-73.8 mV). Perfusion with a low Ca2+ (0.5 mM)/high Mg2+ (8 mM) medium or with tetrodotoxin (1 microM), which blocked synaptic transmission, also reduced the glutamate IPSP. Therefore the glutamate IPSP may be mediated indirectly by inhibitory interneurons. The GABAA antagonist bicuculline (10 microM), or picrotoxin (10-20 microM), blocked the early IPSP, but not the glutamate IPSP. The GABAB antagonist phaclofen (1 mM) attenuated the late IPSP, but did not affect the glutamate IPSP. The results of these experiments suggest that glutamate stimulation of interneurons in stratum lacunosum-moleculare evokes a slow IPSP different from the GABA-mediated early and late IPSPs in CA1 pyramidal cells of the hippocampus.     

Evidence that guanosine triphosphate (GTP)-binding proteins control a synaptic response in brain: effect of pertussis toxin and GTP gamma S on the late inhibitory postsynaptic potential of hippocampal CA3 neurons

These experiments show that a synaptic response in brain, namely, the late inhibitory postsynaptic potential (IPSP) of hippocampal CA3 neurons in the rat hippocampal slice, was blocked by 2 compounds affecting guanosine triphosphate (GTP)-binding proteins. The first of these compounds, pertussis toxin, an inactivator of several GTP-binding proteins (G-proteins), excluding the GTP-binding protein that stimulates adenylyl cyclase, was injected intrahippocampally. The second compound, GTP gamma S, a nonhydrolyzable analog of GTP, was injected directly into postsynaptic neurons via the recording electrode. An ADP-ribosylation assay verified that the pertussis toxin had modified a major portion of the hippocampal pertussis toxin substrates of approximately 40,000 apparent molecular weight. Each agent blocked the conductance associated with both the late IPSP and the response to baclofen, an agonist for a putative receptor mediating the late IPSP (GABAB). These compounds did not block the mossy fiber excitatory postsynaptic potential (EPSP), the GABAA-mediated early IPSP, or the response to the GABAA agonist 4,5,6,7-tetrahydroisoxazolo-(5,4-C)-pyridin-3-ol. It is possible that these measurements underestimated the degree of blockade of the specific potassium conductance of the late IPSP since at least a portion of the GTP-gamma S-insensitive response was not a potassium conductance at all. Rather, it was a response with a reversal potential some 30 mV positive to that of the late IPSP. On the basis of these experiments, I propose that the transmitter receptor of the late IPSP activates a potassium conductance via a G-protein that is sensitive to blockade by pertussis toxin and that GTP gamma S and baclofen activate a conductance that depends upon the same G-proteins and/or potassium channels as does the late IPSP.     

Suppression of the "fast" IPSP when superimposed on the "slow" IPSP as a possible cause of priming in the mouse hippocampus

Extra- and intracellular responses of the mouse hippocampus were recorded at CA1 region after stimulation of two independent inputs from the Schaffer collateral/commissural fibres: conditioning or priming input (C1) and testing or primed one (C2). Duration and amplitude of primed field potentials (FP) and excitatory postsynaptic potentials (EPSP) as well as amplitudes of early (IPSPa) and late (IPSPb) components of inhibitory postsynaptic potentials (IPSP) were measured with variation of C1-C2 intervals from 0 to 1 s. An increase in the FP duration as well as EPSP duration and amplitude and suppression of the IPSP amplitude occurred after conditioning with intervals of 50-500 ms, maximal effect was at 200 ms ("priming" effect). These changes correlated with the amplitude of priming IPSPb. The most prominent effect was observed in cells with hyperpolarizing IPSPa. It is assumed that primed FP and EPSP increase due to suppression of the primed IPSPa, when it is superimposed on the priming IPSPb.     

Kindling induces transient fast inhibition in the dentate gyrus--CA3 projection

The granule cells of the dentate gyrus (DG) send a strong glutamatergic projection, the mossy fibre tract, toward the hippocampal CA3 field, where it excites pyramidal cells and neighbouring inhibitory interneurons. Despite their excitatory nature, granule cells contain small amounts of GAD (glutamate decarboxylase), the main synthetic enzyme for the inhibitory transmitter GABA. Chronic temporal lobe epilepsy results in transient upregulation of GAD and GABA in granule cells, giving rise to the speculation that following overexcitation, mossy fibres exert an inhibitory effect by release of GABA. We therefore stimulated the DG and recorded synaptic potentials from CA3 pyramidal cells in brain slices from kindled and control rats. In both preparations, DG stimulation caused excitatory postsynaptic potential (EPSP)/inhibitory postsynaptic potential (IPSP) sequences. These potentials could be completely blocked by glutamate receptor antagonists in control rats, while in the kindled rats, a bicuculline-sensitive fast IPSP remained, with an onset latency similar to that of the control EPSP. Interestingly, this IPSP disappeared 1 month after the last seizure. When synaptic responses were evoked by high-frequency stimulation, EPSPs in normal rats readily summate to evoke action potentials. In slices from kindled rats, a summation of IPSPs overrides that of the EPSPs and reduces the probability of evoking action potentials. Our data show for the first time that kindling induces functionally relevant activity-dependent expression of fast inhibition onto pyramidal cells, coming from the DG, that can limit CA3 excitation in a frequency-dependent manner.     

Hyperpolarizing synaptic potentials evoked in CA1 pyramidal cells by glutamate stimulation of interneurons from the oriens/alveus border of rat hippocampal slices. I. Electrophysiological response properties

To examine the inhibitory postsynaptic potentials (IPSPs) elicited in pyramidal cells by interneurons situated at the stratum oriens/alveus border (O/A), glutamate was applied by micropressure to this area during intracellular recordings from CA1 pyramidal cells. Glutamate stimulation evoked IPSPs (glut-IPSPs) of small amplitude (4 mV), delayed peak latency (100–110 ms), and long duration (300–400 ms). Recurrent activation of interneurons via glutamate stimulation of pyramidal cells by local application in stratum pyramidale (PYR) evoked recurrent IPSPs (PYR glut-IPSPs) with similar amplitude and time course as O/A glut-IPSPs. The mean equilibrium potential of O/A glut-IPSPs (?77 mV) was significantly different from that of the PYR glut-IPSPs (?71 mV), however, neither equilibrium potential was significantly different from that of the electrically evoked early IPSP in the same cells. Glutamate-evoked IPSPs elicited from O/A displayed some response reversal (27% reversal) like those evoked from PYR (41% reversal). The early IPSP evoked by electrical stimulation displayed significantly more response reversal (67% reversal) than glut-IPSPs. Both types of glut-IPSPs (O/A and PYR) were associated with moderate increases in membrane conductance (5.9 and 6.6 nS, respectively), which were significantly less than the conductance change associated with the early IPSP (45.8 nS). In interneurons within PYR, glutamate stimulation in PYR readily elicited a flurry of excitatory postsynaptic potentials, whereas glutamate stimulation in O/A elicited IPSPs. The electrophysiological properties of IPSPs elicited in pyramidal cells by glutamate stimulation of interneurons in O/A were similar to those of recurrent IPSPs evoked from PYR. Given that both of these types of glutamate-evoked IPSPs were mostly mediated via GABA_A receptor channels (Samulack DD, Lacaille J-C, 1993, Hippocampus 3:345–358), the small differences observed between equilibrium potentials, response reversals, and conductance changes could be due to a more electrotonically distant location from the soma of the synapses involved in O/A glut-IPSPs as compared to those of recurrent IPSPs elicited from PYR.     

Sustained and selective block of IPSPs in brain slices from rats made epileptic by intrahippocampal tetanus toxin.

A small dose of tetanus toxin (2-5 ng; 10 mouse LD50) injected into the rat hippocampus produces a chronic epileptic syndrome in which epileptic discharges recur intermittently for 6-8 weeks. Hippocampal slices prepared during this period and maintained in vitro generate both evoked and spontaneous epileptic discharges. The present study used slices prepared 8-18 days after injection of tetanus toxin or vehicle solution into both hippocampi to test whether or not synaptic inhibition was selectively impaired in this experimental epilepsy. Intracellular recordings were made from CA3 pyramidal layer neurones within the tetanus toxin focus, which was identified by field potential recordings of synchronous bursts evoked by afferent stimulation. The intrinsic properties of these neurones did not differ from comparable cells in control-injected rats. All cells generated excitatory postsynaptic potentials (EPSPs) following stimulation of stratum radiatum in CA3. In control slices EPSPs were followed by a 'fast' inhibitory postsynaptic potential (IPSP), peaking at 25-30 ms, with a mean amplitude (+/- SEM) of -6.7 mV (+/- 0.66). In the epileptic slices these were absent, and the EPSP prolonged so that the potential at 30 ms was a depolarisation of +6.6 mV (+/- 2.75). The slow IPSP at 120 ms dropped to -0.27 mV (+/- 0.18) from -3.97 mV (+/- 1.43) (11 cells in each group). The loss of IPSPs cannot be attributed to a shift in reversal potentials in the toxin-injected group because no IPSPs were unmasked by current injection (n = 11). IPSPs also occurred spontaneously in the neurones in control slices, with a mean amplitude of -1.30 mV. Their frequency decreased by a factor of 13 in cells from the chronic focus induced by tetanus toxin (P less than 0.0001, analysis of variance), but their amplitude did not change significantly (mean of -1.22 mV). Spontaneous EPSPs were significantly more frequent and slightly smaller in the toxin-injected group (mean amplitudes 1.35 and 1.13 mV respectively). Together these studies support the hypothesis that the chronically recurring seizures induced by low doses of tetanus toxin can be attributed to a substantial, persistent and selective reduction of inhibitory neurotransmission in the hippocampus.     

Lemniscal Input to Identified Neurons of the Central Nucleus of Mouse Inferior Colliculus: an Intracellular Brain Slice Study

Intracellular recordings were performed in 34 neurons in the central nucleus of the inferior colliculus in brain slice preparations of the mouse. Sixteen neurons recorded were stained intracellularly by injection of biocytin and identified as multipolar. After electrical stimulation of the lateral lemniscus, 32 of 34 neurons exhibited postsynaptic potentials (PSPs). Onset latencies of the PSPs were 5.0±2.8 ms (range 2-12 ms), presumably reflecting the lack of a significant monosynaptic input to most of the neurons recorded. An excitatory PSP (EPSP), often followed by a late inhibitory PSP (IPSP), was present in all neurons which received synaptic input. The IPSPs usually had a reversal potential positive to the cell's resting membrane potential, thus working as shunting inhibitors. Superfusion of the slice with the GABA_A antagonist bicuculline resulted in blockade of the IPSP and pronounced prolongation of the EPSP. In 50% of these cases, paroxysmal depolarizing shifts were observed in the presence of bicuculline. Blocking the non-NMDA glutamate receptors with 6,7-dinitroquinoxaline-2,3-dione resulted not only in the total disappearance of EPSPs but also of late IPSPs, indicating that the latter depend on the glutamatergic EPSPs. Furthermore, all neurons recorded must receive substantial innervation from sources within the inferior colliculus, together constituting a complex neuronal network in the inferior colliculus with an important role of the inhibitory neurotransmitter GABA in controlling network properties.     

Inhibitory and excitatory effects of CNS depressants on invertebrate synapses.

(1) The effects of pentobarbital were studied on the membrane properties and synaptic activity of crustacean neuromuscular junction preparations and molluscan neurons. (2) Pentobarbital selectivity depressed in a dose-dependent, reversible manner the exciatory postynaptic potentials (EPSPs) recorded at crustacean neuromuscular junctions without altering either inhibitory postsynaptic potentials (IPSPs) or post-synaptic membrane properties. (3) Pentobarbital depressed cholinergic EPSPs recorded in an identified molluscan neuron and depressed the depolarizing phase of biphasic PSP without affecting the hyperpolarizing phase of the BPSP on the same cell. Facilitation of the EPSP was not affected. (4) Pentobarbital did not appreciably alter the reversal potentials of the EPSP and IPSP. (5) Low concentrations of pentobarbital did not alter the appearance of spontaneously occurring IPSPs, while high concentrations changed the pattern of regular IPSP input to an irregular, burst-like pattern. (6) Pentobarbital and 5 other CNS depressants (cholralose, chloroform, ethanol, and urethane) increased the excitability and altered the current--voltage relations of a cell whose membrane properties have been proposed as a model of presynaptic terminal membranes. The effects were dependent on the species of external divalent cation present. (7) The results in these invertebrate systems may provide insight into the cellular basis of the depressant and excitatory effects of these agents.     

Postnatal development of neuronal connections in cat visual cortex studied by intracellular recording in slice preparation

Postnatal development of neuronal connections in cat visual cortex (area 17) was studied in slice preparations obtained from kittens aged 1–18 weeks after birth and adult cats by recording intracellularly excitatory (EPSP) and inhibitory postsynaptic potentials (IPSP) evoked in cortical cells by stimulation of white matter. The EPSPs were already present in all cells at 1 week of age. Their efficiency assessed by their maximum rate of rise was low initially and increased progressively with age. In contrast, the IPSPs were absent in half of the cells at 1 week and almost all of the cells came to demonstrate inhibition by 9 weeks except for a few layer II-III cells. At all ages about three-quarters of the IPSPs had GABA_A-mediated early and GABA_B-mediated late components with different time course, reversal potential and sensitivity to GABA antagonists, while the remaining IPSPs had only the early component. The efficiency of both IPSPs assessed by the associated conductance increase showed an increase of more than twice from 1 to 5 weeks, reaching the same level as adults. The time course of the development of inhibition demonstrated in this study paralleled the time course of the development of selective visual responsiveness in cortical cells, suggesting that the postnatal maturation of inhibitory connections is a basis of maturation of visual responsiveness.     

单侧液压脑损伤对大鼠双侧海马GFAP表达和CA1区突触传递的影响

目的研究单侧液压脑损伤(FPI)对大鼠双侧海马区胶质纤维酸性蛋白(GFAP)表达和CA1区突触传递的影响。方法建立大鼠单侧液压脑损伤模型,脑标本分为对照组(包括正常对照和假手术对照)、FPI损伤同侧组和FPI损伤对侧组。免疫组化法检测海马水平切片GFAP表达,对海马CA1区锥体神经元进行细胞内记录。结果FPI大鼠双侧海马齿状回门区和CA1区GFAP表达均比对照组明显增强。FPI损伤同侧组兴奋性输入-输出关系曲线的斜率比其他两组显著增大(P<0.05);FPI损伤同侧组和对侧组双脉冲易化(PPF)比值和抑制性突触后电位(IPSP)幅值均比对照组显著减小(P<0.05);FPI损伤同侧组和对侧组双脉冲抑制(PPD)比值均比对照组显著增大(P<0.05)。结论大鼠单侧液压脑损伤对双侧海马均可产生影响,导致双侧海马CA1区兴奋性突触传递增强,抑制性突触传递减弱。     

Effects of phenytoin on pyramidal neurons of the rat hippocampus

The effectsof phenytoin (35 μg/ml) on membrane properties and inhibitory postsynaptic potentials (IPSPs) in CA1 and CA3 pyramidal neurons of the in vitro rat hippocampus were examined. No significant change was observed on input resistance or resting membrane potential. Action potential amplitude, overshoot, rate of rise and rate of decay were decreased. IPSP conductance increase and reversal potential, evoked in CA3 cells through mossy fiber stimulation and in CA1 cells through recurrent and Schaffer's collateral stimulation, were unaffected.     

Depression of glutamatergic and gabaergic synaptic responses in striatal spiny neurons by stimulation of presynaptic GABAB receptors

The influence of γ-aminobutyric acid_B (GABA_B) receptor stimulation on the excitatory and inhibitory synaptic potentials and membrane properties of identified striatal spiny neurons was examined in a corticostriatal slice preparation. Stimulation of the subcortical white matter evoked a monosynaptic, excitatory postsynaptic potential (EPSP) and a polysynaptic, inhibitory postsynaptic potential (IPSP) in spiny neurons. The EPSP had two components: a large amplitude response which could be blocked by the kainate/quisqualate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10μM), and a small amplitue, long-duration depolarization which could be blocked by the N-methyl-D-aspartate receptor antagonist, d-(-)-2-amino-5-phosphonovaleric acid (APV, 100 μM). The IPSP was observed as a membrane depolarization when recorded from neurons at resting membrane potential. However, when neurons were injected with the Na⁺-channel blocker, QX-314, allowing cells to be depolarized above their spike thresholds, a prominent hyperpolarizing IPSP was readily observed which could be blocked by the GABA_A antagonist, bicuculline (10-50 μM). This bicuculline-sensitive IPSP was responsible for the inhibition of EPSP amplitude and probability of spike discharge revealed using paired stimulation of the subcortical white matter. The amplitude of both the EPSP and the IPSP were depressed by the GABA_B receptor agonist, p-chlorophenyl-GABA (baclofen, 0.5-100 μM) in a concentration-dependent manner. Baclofen also blocked paired stimulus inhibition of spike discharge. These effects of baclofen persisted in slices in which the cortex was removed and were reversed by the GABA_B receptor antagonist, 3-amino-3-hydroxy-2-(4-chlorophenyl)-propanesulphonic acid (saclofen, 100-500 μM). In contrast to its profound influence on synaptic input, baclofen did not alter resting membrane potential, input resistance, membrane current-voltage relationship, or spike threshold of the cells recorded, and therefore did not appear to exert direct postsynaptic effects on the striatal spiny neurons. Taken together, these data indicate that the depressant effects of baclofen on EPSPs are mediated through GABA_B receptors located on the terminals of glutamatergic afferents within the striatum. Moreover, the results suggest that the actions of baclofen on IPSPs and paired stimulus inhibition are produced by activation of GABA_B receptors within the striatum at a site presynaptic to spiny neurons, either on the terminals of GABAergic afferents or on an interposed non-spiny GABAergic cell. Thus, GABA_B hetero- and auto-receptors have the capacity to provide a negative feedback mechanism through which the major excitatory and inhibitory inputs to striatal spiny neurons are regulated. © 1993 Wiley-Liss, Inc.     

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.     

青蛙前视盖与视顶盖间神经传导的细胞内电生理研究(英文)

目的已有许多研究报告了青蛙的前视盖对视顶盖起抑制作用,但关于此神经活动的特性尚不清楚。本研究探讨了这种复杂的神经活动的机理。方法用细胞内记录方法,通过电刺激前视盖的神经细胞核来记录视顶盖细胞的神经活动。结果前视盖的电刺激在同侧视顶盖主要唤起了两种神经反应:一种是兴奋性(excitatory postsynaptic potential,EPSP)和抑制性突触后电位(an inhibitory postsynaptic potential,IPSP)同时出现,另一种是单纯的IPSP,后者在本记录中占主导地位。另外我们也记录到了某些投射到前视盖的视盖投射细胞的神经电位。它揭示了视顶盖和前视盖之间存在着交叉性的相互作用。短潜时的EPSP可能是通过单突触进行传导的,而大多数的IPSP是通过多突触方式进行神经信息传递的。几乎98%被记录的视盖细胞对前视盖的刺激显示出了抑制性反应。结论前视盖的神经细胞对视顶盖的神经活动发挥了强烈的抑制性作用。     

Neuropeptide FF inhibition of morphine effects in the rat hippocampus

Opioids have an excitatory effect on CA1 pyramidal neurons in the hippocampus due to the inhibition of γ-aminobutyric acid (GABA) release from interneurons. Electrophysiologically, this pyramidal cell excitation is manifest as an increase in extracellularly recorded population spikes, while the reduction in synaptic GABA release is manifest as a decrease in the amplitude of intracellularly recorded inhibitory postsynaptic potentials (IPSPs). Recent studies suggest that some of the behavioral effects of opioids, such as antinociception, can be inhibited antiopioid peptides such as neuropeptide FF (NPFF). In the present study, we have used the hippocampal response to opioids to examine the potential interactions between morphine and NPFF in vitro. Morphine alone (20–200 μM) caused reversible concentration-dependent increases in population spikes and decreases in IPSPs. In extracellular experiments, NPFF (1 μM) alone had no effect on population spikes, but significantly and concentration-dependently inhibited the morphine-induced increases in these responses. Intracellular experiments indicated that while NPFF had no effect on IPSP amplitude, or other pyramidal neurons membrane properties (membrane potential, input resistance, afterhyperpolarization, action potential frequency), it significantly reduced the decrease in IPSP amplitude caused by morphine. These results demonstrate that NPFF can attenuate the effects of morphine on population spikes and IPSPs in the hippocampus, and suggest that this effect occurs at a presynaptic site, possibly involving GABAergic interneurons.     

青蛙前视盖与视顶盖间神经传导的细胞内电生理研究

目的已有许多研究报告了青蛙的前视盖对视顶盖起抑制作用,但关于此神经活动的特性尚不清楚。本研究探讨了这种复杂的神经活动的机理。方法用细胞内记录方法,通过电刺激前视盖的神经细胞核来记录视顶盖细胞的神经活动。结果前视盖的电刺激在同侧视顶盖主要唤起了两种神经反应：一种是兴奋性（excitator ypostsynaptic potential,EPSP）和抑制性突触后电位（an inhibitory postsynaptic potential,IPSP）同时出现,另一种是单纯的IPSP,后者在本记录中占主导地位。另外我们也记录到了某些投射到前视盖的视盖投射细胞的神经电位。它揭示了视顶盖和前视盖之间存在着交叉性的相互作用。短潜时的EPSP可能是通过单突触进行传导的,而大多数的IPSP是通过多突触方式进行神经信息传递的。几乎98％被记录的视盖细胞对前视盖的刺激显示出了抑制性反应。结论前视盖的神经细胞对视顶盖的神经活动发挥了强烈的抑制性作用。