Postsynaptic calcium is necessary for the induction of LTP and LTD of monosynaptic EPSPs in prefrontal neurons: an in vitro study in the rat.
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Animals↗
Biomedical subjects
J C Hirsch
Publications and source records attributed to J C Hirsch.
Homo- and heterosynaptic changes in efficacy are expressed in prefrontal neurons: an in vitro study in the rat.
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2-Amino-5-phosphonovalerate↗
Blockade of NMDA receptors unmasks a long-term depression in synaptic efficacy in rat prefrontal neurons in vitro.
All the experiments were carried out in slices of rat prefrontal cortex maintained in vitro. The effect of 2-amino-5-phosphonovalerate (APV) was tested on the postsynaptic potential (PSP) recorded in layer V pyramidal cells, in response to single or high frequency stimulation of the superficial layers I-II. Wash-out of Mg2+ increased the amplitude and duration of the PSPs. This effect resulted from activation of N-methyl-D-aspartate (NMDA) receptors since it was suppressed by bath application of APV. Furthermore, in every cell tested in Mg2+ containing medium (N = 16), exposure to APV reversibly reduced both mono- and polysynaptic components of the PSPs, indicating that, even in the control solution, activation of NMDA-coupled channels contributed to these synaptic events. Finally, the anomalous voltage-dependence of the EPSP in the presence of Mg2+ and its sensitivity to APV suggests that at least a fraction of the NMDA receptors are postsynaptically located. Tetanization was applied to the afferents of cells bathed in control- or APV-medium. Long-term potentiation (LTP) or long-term depression (LTD) is defined as an increase or a decrease respectively, of the PSPs peak amplitude or initial slope, lasting 20 min. In the control medium, LTP in synaptic efficacy was observed in 34% of the cells and LTD in 48% (N = 23). When exposed to APV, none of the cells tested (N = 16) showed LTP of the response. In contrast, the tetanus induced a LTD of the PSP amplitude or slope in 14 out of these 16 cells. The percentage of cells showing LTD in synaptic efficacy (87%) when the NMDA receptors activation was blocked was significantly higher than that in control-medium.
2-Amino-5-phosphonovalerate↗
Use-dependent changes in synaptic efficacy in rat prefrontal neurons in vitro.
1. An in vitro slice preparation of rat prefrontal cortex was used to analyse the responses of layer V pyramidal cells to electrical stimulation of layer II. We also studied the long-lasting modifications of synaptic efficacy following high-frequency stimulation of the same region. 2. Stable intracellular recordings were obtained from forty-three regular spiking pyramidal cells. The input resistance was 56 +/- 18 M omega (mean +/- S.D.) at a resting membrane potential of -71 +/- 4 mV. 3. At rest, a single stimulus of increasing strength evoked a monophasic, purely depolarizing postsynaptic potential (PSP) of increasing amplitude. In neurons recorded with potassium acetate-filled micropipettes, membrane depolarization disclosed an excitatory-inhibitory (EPSP-IPSP) sequence (onset latency of the EPSP, 3.6 +/- 0.6 ms). 4. Superfusion with the non-N-methyl-D-aspartate (NMDA) receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) reduced the EPSP and suppressed the IPSP. The small EPSP which remained was blocked by the NMDA receptor antagonist, D,L-2-amino-5-phosphonovalerate (APV). 5. In five cells, administration of 0.5 mumol l-1 bicuculline revealed a postsynaptic NMDA component in the evoked response as evidenced by its anomalous voltage dependence in the presence of Mg2+ and its sensitivity to APV. In these cells the latency of the APV-sensitive EPSP was the same as that of the APV-insensitive EPSP. 6. In six cells superfused with a high-Mg2+, low-Ca2+ artificial cerebrospinal fluid (ACSF) a small monosynaptic EPSP remained which had the same latency as the PSP recorded in control ACSF. 7. Patterned high-frequency stimulation (50-100 Hz) was applied to the afferents of twenty-eight neurons (twenty-three of them were recorded in the presence of bicuculline). During the train the membrane potential depolarized some 20 mV and each stimulus evoked a small PSP. The tetanic stimulation was followed by a short-term enhancement of the PSP amplitude and a slight increase in membrane input resistance. 8. Out of the twenty-eight cells, twenty-four showed long-lasting (over 30 min) modifications of the PSP. Long-term depression (LTD) of the evoked PSP was observed in fourteen cells and long-term potentiation (LTP) in ten cells. There was no significant change in the steady-state membrane properties and in the latency of the response. 9. In 64% of the cells that showed LTD and 70% of those that showed LTP of synaptic efficacy, the latency of the enhanced or depressed component of the PSP was the same as the control.(ABSTRACT TRUNCATED AT 400 WORDS)
Action Potentials↗
Cefotaxime for cesarean section prophylaxis in labor. Intravenous administration vs. lavage.
To compare the efficacy of antibiotic prophylaxis through uterine lavage in women undergoing cesarean section in labor to the efficacy of the more standard, perioperative intravenous method, we prospectively randomized 100 women to receive either 2 g of cefotaxime in 1,000 mL of normal saline with a lavage protocol or 1 g of cefotaxime intravenously after cord clamping followed by 1-g doses 6 and 12 hours later. The two groups were similar with respect to age, gestational age, race, weight, length of labor and of ruptured membranes, use of internal monitoring, blood loss and number of vaginal examinations. Standard febrile morbidity and postpartum endomyometritis requiring antibiotic therapy occurred in 18% and 12%, respectively, of the lavage group and in 16% and 12%, respectively, of the intravenous group. Before the routine use of prophylactic antibiotics for cesarean section in labor on our service, the febrile morbidity and endomyometritis rates were 36% and 32%, respectively. The results confirm the benefit of prophylactic antibiotics for cesarean section in labor and demonstrate that the lavage and intravenous methods are similar with respect to efficacy.
Adult↗
Reticular control of thalamic transmission during behavioral states: a study in dorsal lateral geniculate nucleus relay neurons of the cat.
In behaving cats adapted to head restraint we examined the changes of spontaneous activity of dorsal lateral geniculate relay neurons provoked by weak stimulation of mesencephalic reticular formation during different states of sleep and alertness. The neurons were classified as fast- and slow-conducting neurons depending on their optic tract latency. When the reticular stimulation was delivered during slow-wave sleep, it increased the firing rate principally in slow neurons and suppressed the burst pattern. The increases occurred on a long depolarization in intracellular recordings (n = 9). The effect resembled one that was simultaneous with pontogeniculooccipital waves. Only slow neurons showed a correlation between the relative increases and the prestimulus firing rate. The excitatory effect was reduced and less frequent during wakefulness and paradoxical sleep in both latency groups. When reticular stimulation did not influence the spontaneous activity of the activated states, it also did not modify the optic tract-elicited hyperpolarization. The data tend to demonstrate that the efficiency of the reticular stimulation depends principally on the rate and pattern of the spontaneous activity which, itself, varies largely according to the behavioral state and moderately according to the optic tract latency.
Animals↗
A synaptically evoked late hyperpolarization in the rat dorsolateral geniculate neurons in vitro.
Intracellular potentials were recorded from presumed relay neurons in the rat dorsolateral geniculate nucleus maintained in vitro preparations. In this material, the neuronal circuit includes the excitatory optic tract which innervates monosynaptically both relay and intrinsic neurons, the latter providing a feed-forward GABAergic inhibition on the former. Electrical stimulation of the optic tract evokes in the dorsolateral geniculate neurons an early excitatory postsynaptic potential followed by an inhibitory postsynaptic potential which precedes a so far unreported long-lasting late hyperpolarization. The properties of the inhibitory postsynaptic potential are consistent with the notion that they are of disynaptic (feed-forward) origin and that they are the consequence of GABAA receptor activation. In contrast, the late hyperpolarization, which was found in almost every neuron, was enhanced by GABAA blockers, without accompanying changes in the resting membrane potential or the input resistance of the recorded cells. The late hyperpolarization had a lower threshold than the excitatory postsynaptic potential, a long latency (m = 38 +/- 4 ms, n = 10) and was of long duration (m = 308 +/- 57 ms, n = 10). The occurrence and threshold for producing these two potentials were uncorrelated, and paired stimulations of the optic tract showed a marked difference of their recovery time-courses. The late hyperpolarization could be elicited only by afferent stimulations; it never followed intracellularly induced depolarizations and/or anodal break calcium spikes. It was associated with a small conductance increase, sufficient, however, to inhibit high-frequency discharges induced by intracellular injection of depolarizing currents. The late hyperpolarization decreased in amplitude with membrane hyperpolarization and ultimately reversed polarity. The apparent reversal potential followed shifts in extracellular potassium concentration in an almost Nernstian relation (47 mV for a tenfold increase in [K]0). Involvement of GABAB receptors in the generation of this potential may be postulated since baclofen readily hyperpolarized the neurons and decreased their input resistance in the presence of GABAA blockers. We conclude that the late hyperpolarization is a postsynaptic potential mediated by an increased conductance to K ions. Our results further suggest that a minimal disynaptic feed-forward circuit impinging on the relay neurons of the dorsolateral geniculate nucleus is sufficient to subserve this late hyperpolarization.(ABSTRACT TRUNCATED AT 400 WORDS)
Action Potentials↗
Comparison of ceforanide and cephalothin prophylaxis in patients undergoing total joint arthroplasty.
One hundred one patients undergoing total hip and knee arthroplasty were randomly assigned to receive either two 1 gm doses of ceforanide or five doses of cephalothin perioperatively. Simultaneous plasma and cancellous bone specimens were obtained intraoperatively and assayed for antibiotic concentration. Ceforanide plasma and bone levels remained sustained over six hours. Cephalothin plasma and bone levels obtained three to four hours post administration were 91% lower than levels obtained one hour post-dose. Patients were examined for infection for up to 18 months following surgery. None of the patients developed an infected implant. The sustained plasma and bone levels achieved with ceforanide obviate the need for intraoperative dosing necessary with other agents.
Adult↗
Randomized, comparative trial of imipenem/cilastatin and moxalactam in the treatment of serious obstetric and gynecologic infections.
Thirty-four patients with pelvic inflammatory disease, postoperative, postabortal and postpartum infections were randomized to intravenous therapy with either 500 milligrams of imipenem and cilastatin sodium every six hours or 2 grams of moxalactam every eight hours for a minimum of four days. One patient in the moxalactam group was nonevaluable because of protocol noncompliance; three more patients had no bacteriologic pathogen isolated (two in the moxalactam group and one patient in the imipenem/cilastatin group). The two groups were similar with respect to age, diagnosis, etiologic agents and duration of therapy. Of the 17 evaluable patients in the imipenem/cilastatin group, all were complete clinical cures. Three patients in the imipenem/cilastatin group had persistence of at least one bacteriologic pathogen despite clinical cure and apparent laboratory evidence of susceptibility. Of the 13 evaluable patients in the moxalactam group, eight were complete clinical cures. Two more patients in that group were clinically improved enough to be discharged on oral antibiotics. There were three clinical failures in the moxalactam group, all of whom had group D streptococcus resistant to moxalactam. An additional three patients in the moxalactam group had other resistant organisms isolated despite clinical cure. Both drugs were well tolerated and no serious complications or side effects occurred in either group. Despite small numbers, our data suggest that imipenem and cilastatin is a more appropriate agent for initial treatment of obstetric and gynecologic infections than moxalactam.
Acute Disease↗
Dorsolateral geniculate neurons in vitro: reduced postsynaptic excitability following repetitive activation of the optic tract.
Monosynaptic activation of dorsolateral geniculate neurons of the rat was studied in the in vitro slice preparation. (1) As previously described by others, monosynaptic excitatory postsynaptic potentials (EPSPs) trigger at membrane potential negative to -60 mV a low threshold spike (Lts). In addition, we report that the Lts amplitude is linked to that of its underlying EPSP. (2) EPSPs, EPSP-Lts sequences and nonsynaptic Lts are followed by a long period of refractoriness during which a test response is decreased in amplitude and the Lts component is cut off. These results are discussed in relation to the generation of spontaneous bursting activity of thalamic neurons during natural sleep, which could be accounted for by the properties of the Lts alone.
Animals↗
Oscillations of the spontaneous slow-wave sleep rhythm in lateral geniculate nucleus relay neurons of behaving cats.
Intracellular recordings of 31 lateral geniculate nucleus relay neurons were performed in darkness in behaving cats in order to analyse electrical postsynaptic events which appeared during slow-wave sleep. A specific pattern characterized slow-wave sleep: a rapid depolarizing potential arising from baseline initiated a slow depolarization lasting for 40-60 ms which in turn most often elicited delayed fast spikes. This pattern recurred at a frequency of 6-12/s. The slow depolarizations were voltage dependent, usually not separated by any obvious phasic hyperpolarization and showed refractoriness. Other rapid depolarizing potentials occurring during the time course or at the end of a slow depolarization could have generated spike(s) but were followed by a rapid decay. Slow depolarizations were not observed during arousal or paradoxical sleep when the neurons tonically depolarized and displayed either rapid depolarizing potentials with a fast decay or repetitive firing and long high frequency bursts. In five of the studied neurons, decreases in frequency of the spontaneous rapid depolarizing potentials occurred during slow-wave sleep for 3-30 s oscillatory periods without any change in the behavioural state. During these periods all of the few remaining rapid depolarizing potentials arose from a flat baseline, had a higher amplitude and initiated a slow depolarization which always elicited a spike or burst of spikes after a brief delay. The slow-wave sleep rhythm decreased to 1-5/s. Simultaneously the baseline membrane potential hyperpolarized by a few millivolts and reached a level for reversal of inhibitory postsynaptic potentials. Imposed hyperpolarization of the membrane during wakefulness did not reveal any slow depolarization. But strong synaptic excitatory inputs and direct excitation (a break of the current pulse) from a hyperpolarized membrane did evoke the slow depolarization and eventually the fast spike(s) in both control and oscillatory neurons. A rhythm similar to that of slow-wave sleep was elicited during wakefulness by optic tract stimulation and was enhanced by membrane hyperpolarization. But under these conditions the rhythm was initiated by a phasic hyperpolarization and was composed of an alternating hyperpolarization-depolarization. Spontaneously and synaptically evoked rapid depolarizing potentials arising from baseline had a similar rising slope. The spontaneous ones initiated a slow depolarization leading to fast spike(s) during slow-wave sleep and could directly generate fast spike(s) during wakefulness.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Controlled, comparative study of moxalactam and cefazolin for prophylaxis of abdominal hysterectomy.
Moxalactam was compared with cefazolin and a control group to determine the efficacy and value of a third generation cephalosporin in abdominal hysterectomy antibiotic prophylaxis. One hundred patients were prospectively randomized in a double-blind manner between moxalactam and cefazolin. An additional 50 patients who were either allergic to penicillin or refused participation in this study were simultaneously observed to establish a base line level of infection on our service during this time period. Dosage for both antibiotic groups was 1 gram given intravenously or intramuscularly on call to the operating room followed by two 1 gram doses at six and 12 hours after the first dose. Standard febrile morbidity was 36, 30 and 42 per cent for moxalactam, cefazolin and control groups, respectively. Postoperative surgical infection requiring antibiotic treatment occurred in 8, 6 and 4 per cent, respectively; urinary tract infection or symptomatic findings, or both, requiring treatment occurred in 8, 10 and 10 per cent, respectively. No pelvic abscesses occurred in this series. In every statistical evaluation of postoperative morbidity, there were no differences noted among the three groups. Our results suggest no benefit from the use of prophylactic antibiotics in abdominal hysterectomy in terms of standard febrile or infectious morbidity or urinary tract pathologic findings. In addition, there was no difference between the two antibiotic groups.
Adolescent↗
The potential of digitally inserted tampons to induce vaginal lesions.
To determine the incidence of vaginal mucosal alterations associated with the use of digitally inserted tampons, 100 women were prospectively evaluated colposcopically for three consecutive menstrual cycles. Three groups of 20 women each used the regular, super, and super-plus sizes of a digitally inserted rayon and cotton tampon; two additional groups of 20 each used external sanitary protection or an applicator-inserted rayon polyacrylate tampon. Vaginal mucosal drying and layering were significantly more common in all tampon users than in pad users; vaginal mucosal ulceration was a more rare event, seen only in tampon users, and statistically more commonly in the rayon polyacrylate group. The incidence of these alterations was not related to the presence of Staphylococcus aureus. All ulcerations healed without treatment. The common occurrence and relatively benign nature of these changes are discussed in view of the concern that these changes might predispose a woman to developing toxic shock syndrome.
Adolescent↗
Modulation of postsynaptic activities of thalamic lateral geniculate neurons by spontaneous changes in number of retinal inputs in chronic cats. 1. Input-output relations.
The experiments were designed to explore the role of retinal inputs compared with that of the behavioral state in the modulation of the output of thalamic lateral geniculate neurons during sleep and wakefulness in cats with intact visual pathways. We made the following assumptions: the retinal dark discharge, while showing spontaneous pauses in activity, does not vary with the behavioral state; the optic tract inputs postsynaptically elicit subthreshold activities called S-potentials which in turn generate spikes, the degree of transformation being dependent on the level of alertness. On the basis of these assumptions, it could be expected that changes in retinal input frequency would modify the rate of the S-potentials. Therefore the effect of spontaneous decreases in frequency of S-potentials on the spike rate and pattern was examined in juxta- and intracellular recordings from chronically implanted cats during natural sleep and wakefulness. During quiet wakefulness and light slow-wave sleep, lateral geniculate relay neurons normally displayed numerous S-potentials associated with a moderate firing rate. Many neurons occasionally showed transient reductions in frequency of the S-potentials and an oversimplification of the discharges which combined a decreased rate with a prevalent rhythmical burst pattern. Antidromic responsiveness remained unchanged. The oscillatory periods recurred two to six times without any alteration in the control state level. They were not observed throughout wakefulness and paradoxical sleep, during which neuronal activity combined a high spike rate with a low S-potential rate. The modifications were confirmed by computation of the mean rates and of the inter-event intervals. The transfer ratio (spikes/S-potentials + spikes) significantly increased both during the oscillatory periods poor in S-potentials of quiet wakefulness and during active wakefulness. But the correlation between the transfer ratio and the spike frequency, which was high throughout the control behavioral states, faded during the periods poor in S-potentials. Thus the transient falls in the frequency of S-potentials which occurred spontaneously during quiet wakefulness caused burst discharges in lateral geniculate relay neurons, which resembled a sleep deepening, but also paralleled the effect of experimental deafferentation. The data indicate that the iterative spikes grouped in well spaced bursts which persisted during decreases in subthreshold postsynaptic activities result in an enhanced signal-to-noise ratio.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
The effect of midbrain reticular stimulation upon perigeniculate neurons activity during different states of the sleep-waking cycle in the cat.
Electrical stimulation of the mesencephalic reticular formation in chronic cats induced state-dependent effects on spontaneous firing of perigeniculate neurons. Perigeniculate neurons fired at lower rates during slow wave sleep than during wakefulness of paradoxical sleep. The stimulation caused a firing decrease in slow wave sleep; an effect which faded during wakefulness and paradoxical sleep and was superseded by a firing increase during periods of eye movements in 30% of the neurons. The responsiveness of perigeniculate neurons to optic tract and visual cortex stimulation either remained unchanged or was enhanced during the reticular induced firing changes.
Animals↗
Sleep-related variations of membrane potential in the lateral geniculate body relay neurons of the cat.
Membrane potential of lateral geniculate body relay neurons was monitored in chronic cats during the sleep-waking cycle. Neurons were tonically depolarized throughout paradoxical (P) sleep and the maximal level of polarization occurred during slow (S) sleep (mean difference of membrane potential between S and P sleep: + 10.2 +/- 1.3 mV, n = 6, range: 8-12 mV). Some features of the spontaneous activity of S and P sleep are briefly discussed in relation to the level of membrane potential. In particular it is suggested that the phasic depolarizations underlying the bursts of action potentials during S sleep, and which are reproduced retinal cell axons impinging upon the hyperpolarized membrane.
Animals↗
Electrophysiological study of the perigeniculate region during natural sleep in the cat.
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Action Potentials↗
[Effects of a cortical after-discharge on lateral geniculate neurones. Electrophysiological study in the chronic cat (author's transl)].
(1) A chronic preparation is described in which it is possible to record juxtacellularly from identified thalamo-cortical relay (TCR) neurones in lateral geniculate body (LGB) of normally respiring, nonanaesthetized cats during natural sleep. (2) Cellular events were analyzed during and after focal electrical stimulation of homotopic visual cortex. (3) Projection of cortical epileptiform after-discharge (EAD) was strictly limited to functionally related areas of LGB. Of the 47 neurones tested only 30% were activated. (4) During the 2 sec, 50 c/sec tetanus the cortically evoked IPSPs in TCR cells were replaced by facilitation of cortico-thalamic transmission as demonstrated by the occurrence of a burst of action potentials (AP) following the antidromic AP. (5) During the ensuing EAD, high frequency AP discharges occurred in the cortico-thalamic axons during each cortical wave. This period was accompanied by prolonged (50-300 msec) low amplitude rhythmic depolarisations leading to temporary spike inactivation of TCR neurones. Comparable inactivating responses were recorded during paradoxical sleep. (6) Between paroxysmal bursts facilitation of synaptic transmission to the optic tract stimulation was observed. (7) Persistence of a positive collision test after a spontaneous AP indicates that AP are orthodromically propagated during the EAD.
Action Potentials↗