Inhibition Of Phase Research Articles

Unilateral cholinergic stimulation of the rabbit's cerebellar flocculus: asymmetric effects on optokinetic responses

In previous work, we have demonstrated an acceleration of the buildup of slow-phase velocity of optokinetic nystagmus (OKN) after bilateral floccular injection of the aselective cholinergic agonist carbachol (Tan and Collewijn 1991; Tan et al. 1992a). In the present study we investigated the effects of unilateral floccular injections of carbachol. Such unilateral injections specifically enhanced the buildup of OKN slow-phase velocity in the direction toward the injected flocculus (ipsiversive). During binocular optokinetic stimulation, this enhancement was expressed in the motion of both eyes. Acceleration of the eye contralateral to the injected flocculus increased from 1 to about 2 degrees/s2, while the acceleration of the ipsilateral eye increased from 1 to about 1.5 degrees/s2. In contrast, buildup of contraversive OKN was unchanged. No changes were found in the steady-state OKN and optokinetic afternystagmus (OKAN). Monocular optokinetic stimulation was only effective in the nasal direction, and the effects of unilateral injection of carbachol were disconjugate. Ipsiversive OKN was enhanced only in the contralateral, seeing eye, while the response of the ipsilateral, covered eye was unchanged. We hypothesize that the directionally specific effect of unilateral cholinergic floccular stimulation on OKN is due to enhancement of predominantly the excitatory phase of modulation of the Purkinje cell's simple-spike activity by carbachol, without a marked effect of carbachol on the inhibitory phase of simple-spike modulation.

Inhibitory effects of excitatory amino acids on pyramidal cells of the in vitro turtle medial cortex.

The electroencephalogram of the in vitro brain of the turtle Chrysemys d' orbigny shows spontaneous random large sharp waves (LSWs) which may be compared to interictal spikes. In order to evaluate the role of excitatory amino acids (EAAs)--in particular through the N-methyl-D-aspartate (NMDA) receptor--in the generation of LSWs, the bath application of NMDA and its antagonists 3-((+/-)-2-carboxypiperazin-4y)-propyl-1-phosphonic acid (CPP) and DL-2-amino-5-phosphonovaleric acid (APV), was performed in the whole open hemisphere (WOH) in vitro. Field recordings in WOH showed that both CPP and APV unexpectedly increased LSW amplitude. Consistently, NMDA in the bath suppressed the LSWs. Iontophoretically applied glutamate, kainate and NMDA produced a hyperpolarization of intracellularly recorded medial cortex pyramidal cells both in WOH and in slices. The EAA-induced hyperpolarization was tetrodotoxin (TTX) and bicuculline sensitive and reversed close to -70 mV. It would therefore seem to be due to the activation of gamma-aminobutyric acid (GABA) interneurons. The NMDA could also produce an excitation of pyramidal cells--always following a previous inhibitory phase. In some cases rhythmic bursting discharges or plateau potentials were observed. These NMDA effects were mainly elicited by a direct effect on pyramidal cells. A long-lasting hyperpolarizing response following the NMDA excitatory phase was also observed. This long-lasting response was an intrinsic property of pyramidal cells since it was TTX resistant. This study demonstrates that GABAergic interneurons from the turtle medial cortex can be activated by EAAs, a mechanism that can account for the effects of NMDA antagonists on LSWs.

Inhibitory synaptic currents in rat cerebellar Purkinje cells: modulation by postsynaptic depolarization.

1. Synaptic currents were recorded in voltage-clamped cerebellar Purkinje cells using the tight-seal whole-cell recording technique. Cells were dialysed with a CsCl solution and were held at -60 or -70 mV. Inhibitory interneurones (basket and stellate cells) were stimulated using an extracellular pipette positioned in the molecular layer. Blockers of excitatory glutamatergic synapses were included in the bath solution. 2. Evoked synaptic currents were observed after a latency of 3-4 ms. The time course of synaptic currents could in most cases be fitted to a biexponential curve, with a rise time constant, tau on, of 1-3 ms and a decay time constant, tau off, of 7-13 ms. These currents were blocked by bicuculline. 3. The mean amplitude of evoked synaptic currents increased in discrete steps when the voltage applied to the stimulating pipette was increased. At each level, very prominent fluctuations of the amplitude were observed among trials. 4. Complex synaptic currents corresponding to repetitive activity of the presynaptic interneurone were occasionally observed, particularly with high intensity presynaptic stimulation. This repetitive activity could lead to bursts of synaptic currents lasting for several seconds. 5. Following a depolarizing voltage train in the postsynaptic Purkinje cell, the amplitude of evoked synaptic currents was first inhibited, and then potentiated. The inhibition was accompanied by a small but consistent increase in tau off and by no alteration in tau on. When using small intensity presynaptic stimuli, it was found that the probability of failures was greatly enhanced. The inhibitory phase lasted for about 1 min before giving way to potentiation. The potentiation returned to the control with a time to half-decay of 12.9 +/- 0.9 min. 6. The present results give further evidence to a previously proposed hypothesis that the inhibition produced by Purkinje cell depolarization is mainly presynaptic. The longer lasting potentiation, on the other hand, has most probably a postsynaptic origin. Cerebellar Purkinje cells receive inhibitory GABAergic inputs from two classes of interneurones located in the molecular layer (reviewed in Palay & Chan-Palay, 1974; Ito, 1984). Basket cells are closest to the Purkinje cell layer and address their inhibitory signal primarily to the soma and to the main dendrites. Stellate cells are more externally located and have contacts with the more distal part of the dendritic arborization of Purkinje cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Ionic modulation of the effects of heparin on plasminogen activation by tissue plasminogen activator: The effects of ionic strength, divalent cations, and chloride

Ionic strength, divalent cations, and Cl − modulate the ability of the glycosaminoglycan heparin to stimulate the activation of human plasminogen (Pg) by tissue-type Pg activator. Kinetic analysis of Pg activation indicates that heparin is inhibitory, stimulatory, or nonstimulatory as a function of ionic strength. While increasing ionic strength inhibits Pg activation in the absence of heparin, in its presence an activation phase followed by an inhibitory phase is observed. Divalent cations, inhibitors of activation in the absence of heparin, increase the rate of activation in its presence. Kinetic analysis demonstrates that divalent cations augment the heparin stimulatory effect a maximum of 60-fold due to increases in k cat without changes in K m of the reaction. This effect is heparinspecific, since activation is not affected by Ca 2+ in the presence of heparan sulfate or de-N-sulfated heparin. Also, Cl − inhibits Pg activation in the presence of heparin by acting as a competitive inhibitor ( K ic of 100 m m). Furthermore, inhibition by Cl − reduces the overall magnitude of heparin stimulation of Pg activation. These results suggest that physiologic ions in combination with heparin may be significant effectors of Pg activation in the vascular microenvironment.

Expiratory bulbospinal neurons of dogs. I. Control of discharge patterns by pulmonary stretch receptors

To better understand expiratory bulbospinal (EBS) neuronal processing of afferent patterns from slowly adapting pulmonary stretch receptors (PSRs), the responses of these caudal medullary neurons to various inflation patterns were analyzed in thiopental sodium-anesthetized paralyzed dogs. Normocapnic ventilation was obtained from lung inflations delivered during the neural inspiratory phase of control respiratory cycles by a solenoid ventilator triggered by the onset of phrenic nerve activity. Test inflation patterns, delivered during the neural expiratory (E) phase of specific cycles, were separated by 6-10 control cycles and consisted of slow augmenting and decrementing ramps and steps. Transpulmonary pressure (Pt) was used as an index of PSR activity, and the discharge patterns of single EBS neurons were quantified using cycle-triggered histograms. Based on the time course of the discharge pattern during no-inflation cycles, two types of neurons were identified. Type D, the most common, exhibited a decrementing-like pattern, while type A exhibited an augmenting-plateau pattern. Plots of discharge frequency vs. Pt for type D neurons consisted of a linear excitatory phase (1 less than Pt less than 4.6 mmHg) and a linear inhibitory phase (4.6 less than Pt less than 12 mmHg). Type A neurons exhibited only a linear inhibitory phase for 3.3 less than Pt less than 12 mmHg. Because the responses to step inflations (4 s duration) exhibited only a small amount of time dependency, and the activation Pt of PSRs, but not of the other pulmonary receptors with vagal fibers, is in the proper range, it appears that PSRs may mediate both excitatory and inhibitory components of the neuronal response. These data suggest that discharge patterns of the caudal EBS neurons in dogs are highly dependent on the time course of Pt in a predictable manner, and implicate the importance of instantaneous lung volume in the control of the E musculature and the optimization of the breathing pattern.

Prostaglandin E 2 can bimodally inhibit and stimulate the epididymal adipocyte adenylyl cyclase activity

Measurements of prostaglandin E 2 (PGE 2)-induced adenylyl cyclase acivity in membranes isolated from epididymal rat adipocytes revealed inhibition of cAMP production at low concentrations of PGE 2 (<10 mM) and stimulation at higher concentrations. This biphasic effect of PGE 2 was obtained when adenylyl cyclase was stimulated with GTP or NaF. In the presence of forskolin only the inhibitory phase by PGE 2 was observed. Suplprostone, a PGE 2 analogue, did not affect cAMP synthesis in the presence of either GTP or NaF; however, in the presence of forskolin, it inhibited cAMP production similarly to PGE 2. Treatment of the membranes with cholera or pertussis toxin did not alter the biphasic effect of PGE 2 on cAMP production. These findings raise the possibility that PGE 2 acts through several receptor subtypes which are coupled to GTP binding proteins different from the classical Gi or Gs proteins.

Dissociation of serotoninergic and dopaminergic components in acute effects of 1-methy 1-4-pheny 1-1,2,3,6-tetrahydropyridine in mice

Behavioural and neurochemical effects of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment in mice have been studied in order to determine the change in the neurotransmitter profile of the following areas of the brain: substantia nigra (SN), nucleus caudatus putamen (NCP), limbic system (LS tuberculum olfactorium and nucleus accumbens), medulla oblongata (MO) and cerebellum (CER). Subcutaneous administration of MPTP (40 mg/kg) caused behavioural syndromes including restlessness, straub tail, hindlimb abduction, tremor, jumping, bradykinesia and akinesia in Balb/c mice. There existed a well-defined biphasic profile of motor activity comprising of an initial excitatory phase followed by an inhibitory phase lasting about two and a half and five hours, respectively. A significant rise in 5-hydroxytryptamine (5-HT) content together with a decreased 5-HT utilization as evidenced by lower 5-hydroxyindole acetic acid (5-HIAA) to 5-HT ratio in the above brain areas demarcated the excitatory phase, whereas the inhibitory phase was distinguished by a significant decrease in dopamine (DA) content along with an increased turnover of the amine as shown by a higher homovanillic acid (HVA) to DA ratio in the functionally important nuclei of the extrapyramidal system like SN, NCP and LS. Methysergide, a nonspecific 5-HT receptor blocker, but not ketanserin, a specific 5-HT 2 antagonist, prevented the occurrence of the initial excitatory phase without affecting the depressive phase. Administration of apomorphine, a dopamine agonist, 30 minutes prior to MPTP was ineffective, whereas its application 90 minutes after MPTP prevented the occurrence of bradykinesia and akinesia. Interestingly, treatment with haloperidol, the dopamine ( D 1 D 2 ) antagonist, before and after MPTP administration caused an early onset and prolongation of the inhibitory phase without affecting the initial hyperexcitement. The results provide direct evidence for the involvement of Serotoninergic and dopaminergic mechanisms in the genesis of the early and late syndromes of acute MPTP poisoning respectively.

Papaverine reduces the sodium permeability of the apical membrane and the potassium permeability of the basolateral membrane in isolated frog skin.

The effect of papaverine, an inhibitor of the phosphodiesterase responsible for breakdown of cAMP, on the transepithelial sodium transport across the isolated frog skin was investigated. Serosal addition of papaverine caused initially an increase in the short-circuit current (SCC), a doubling of the cellular cAMP content and a depolarization of the intracellular potential under SCC conditions (Vscc). The initial increase in the SCC was followed by a pronounced decrease both in the SCC and in the natriferic action of antidiuretic hormone (ADH), but papaverine had no inhibitory effect on the ability of ADH to increase the cellular cAMP content. As SCC declines, no hyperpolarization was observed. The I/V relationship across the apical membrane during the inhibitory phase, revealed that papaverine reduces the sodium permeability of the apical membrane (PNaa) as well as intracellular sodium concentration. These observations and the previously noted effect of papaverine on Vscc indicates that papaverine must have an effect on the cellular Cl or K permeability. The basolateral Na,K,2Cl cotransporter was blocked with bumetanide, which should bring the cellular chloride in equilibrium. Bumetanide had no effect on basal SCC and Vscc. When papaverine was added to skins preincubated with bumetanide, the effect of papaverine on SCC and Vscc was unchanged. Therefore, the depolarization of Vscc, observed during the papaverine-induced inhibition of the SCC, must be due to a reduction in the cellular K permeability. In conclusion, it is suggested that papaverine reduces the sodium permeability of the apical membrane and the potassium permeability of the basolateral membrane of the frog skin epithelium.

Neurotensin: dual effect on the motor activity of rat duodenum

The effects of neurotensin on mechanical activity of rat duodenum were investigated using an isometric-isovolumic preparation. Neurotensin (1 pM to 10 nM) induced a concentration-dependent, tetrodotoxin (TTX)-insensitive fall in both endoluminal pressure and isometric tension. At higher concentrations of neurotensin (1 nM to 1 μM) the relaxation was followed by a concentration-dependent TTX-insensitive contraction, detected only by an increase in endoluminal pressure. Different concentrations of neurotensin were required to desensitize the relaxant and the contractile actions of the neuropeptide. The relaxation was antagonized by apamin, while the contractile response was blocked by nifedipine. Neurotensin, when tested separately on longitudinal and circular muscular strips, caused relaxation of the longitudinal strips. Circular strips showed contractions in response to neurotensin, following an inhibitory phase, if the strips were spontaneously or pharmacologically activated. The results suggest the presence of two sets of neurotensin receptors with a differential localization between the two muscular layers in rat duodenum.

Characterization of dopamine receptors associated with steroid secretion in frog adrenocortical cells.

We investigated the type of receptors involved in the mechanism of action of dopamine on corticosteroid secretion from the frog interrenal (adrenal) gland, using the in-vitro perifusion technique. Exposure of dispersed interrenal cells to 50 microM dopamine for 20 min had a biphasic effect on corticosterone and aldosterone secretion, i.e. a transient stimulation followed by an inhibitory phase. Repeated administration of equimolar pulses of dopamine, given at 150-min intervals, resulted in an enhancement of corticosteroid secretion followed by a subsequent blockade of the stimulatory phase of the response. In contrast, the dopamine-evoked inhibition of corticosteroid release did not show any sensitization or desensitization phenomena. Infusion of repeated pulses of the D1 receptor agonist SKF38393 (32 microM) stimulated corticosteroid release and mimicked the sensitization-desensitization phenomenon induced by dopamine. Repeated administration of the D2 receptor agonist LY171555 (50 microM) resulted in a reproducible inhibition of corticosterone and aldosterone secretion. These results suggested the presence of two different receptors for dopamine, i.e. D1 and D2, on frog adrenocortical cells, responsible respectively for the stimulatory and inhibitory effects of dopamine on steroid secretion. However, bromocriptine (50 microM) and CV205-502 (50 microM), two other D2 receptor agonists, had no effect on corticosteroid release. In addition, several classical D2 receptor antagonists failed to block the effect of dopamine on steroidogenesis. It was also observed that (-)sulpiride, a specific D2 antagonist, did not alter dopamine-induced inhibition of inositol phosphate formation. On the other hand, dopamine and the selective D1 and D2 antagonists SKF38393 and LY171555 did not affect the formation of cyclic AMP by interrenal tissue. Taken together, these data indicate that dopamine directly regulates corticosteroid secretion from frog adrenocortical cells. The effect of dopamine is not coupled to adenylate cyclase activity but is probably mediated through the phosphoinositide-turnover pathway. The pharmacological characteristics of the receptors involved in the mechanism of action of dopamine clearly differ from those of the D1 and D2 subtypes previously described in mammals.

Adenosine receptor-induced cAMP changes in D384 astrocytoma cells and the effect of bradykinin thereon.

In human D384 astrocytoma cells, cyclic AMP accumulation can be conveniently studied after labelling of the adenosine triphosphate pool (15 fmol cell-1) with [3H]adenine. In this study, adenosine had a biphasic effect on cyclic AMP accumulation, which was scarcely altered by blocking adenosine uptake and metabolism. Low concentrations of adenosine led to an inhibition of cyclic AMP accumulation, and higher concentrations led to stimulation. No effect of adenosine on cyclic AMP was observed unless phosphodiesterase was inhibited by rolipram. The A1 receptor antagonist DPCPX attenuated the inhibitory phase of adenosine response, and enhanced the cyclic AMP accumulation induced by adenosine analogues. The cyclic AMP accumulation was stimulated by NECA greater than ADO greater than CGS 21680 greater than CV 1808 greater than CPA greater than or equal to CHA, indicating mediation by A2 receptors. The stimulatory effect of NECA was much more effectively blocked by the combined A1 and A2 receptor antagonist CGS 15943 (KB 4 nmol l-1) than by the A1 antagonist DPCPX (KB 110 nmol l-1). Treatment of the cells with pertussis toxin (0.2 microgram ml-1 for 2.5 h) potentiated the cyclic AMP response to adenosine analogues significantly. The cyclic AMP response to NECA was enhanced by the protein kinase C activator phorbol dibutyrate even after pertussis toxin treatment. By contrast, nanomolar concentrations of bradykinin, which increases Ca(2+)-levels and protein kinase C activity in D384 cells, reduced NECA-induced cyclic AMP accumulation in control and pertussis toxin-treated cells. Thus, D384 cells possess both A1 and A2 adenosine receptors influencing cyclic AMP in opposite directions.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between mast cell degranulation and jejunal myoelectric alterations in intestinal anaphylaxis in rats

The effects of two degranulators of mast cells and intestinal anaphylaxis on jejunal myoelectric activity were compared in rats fasted for 15 hours. Attempts to antagonize the motility changes were performed using antagonists of histamine and serotonin and a cyclooxygenase and lipoxygenase inhibitor. Hooded Lister rats were chronically fitted with electrodes implanted in the jejunal wall. A group of rats was sensitized to egg albumin and challenged 14 days later by intraduodenal infusion of antigen. Sensitized animals had serum titers ≥ 1:64. The other group was administered with mast cells degranulators. Both 48/80 (1 mg/kg), a degranulator of connective mast cells, and bromolasalocid (2 mg/kg), acting on connective and mucosal mast cells, induced a phase of total spiking inhibition followed by a progressive irregular spiking activity until the recovery of migrating myoelectric complex pattern (about 3 hours after injection). In contrast, antigen challenge disrupted the migrating myoelectric complex pattern, which was replaced by a peculiar pattern characterized by propagated spike burst, lasting 98 ± 11.3 minutes. Chlorpheniramine (1 mg/kg) antagonized only the inhibitory phase induced by degranulators and was ineffective on the intestinal anaphylaxis-induced motor changes. Methysergide (1 mg/kg) and indomethacin (5 mg/kg) significantly reduced the degranulator effects as well as the anaphylaxis-induced alterations of intestinal motility. It is concluded that anaphylaxis-induced motor disturbances are relevant to mucosal mast cell degranulation involving 5-hydroxytryptamine and arachidonic acid derivative products, whereas histamine release appears to be a minor component.

Influence of PGF 2α on gastrointestinal activity in the conscious piglet

In 5 conscious piglets with electrodes implanted on the antrum pylori, duodenum, jejunum and ileum, the effect of intravenous infusion of PGF 2α 1 and 10 μg/kg/min during 2 h, on gastrointestinal electrical activity was studied. The influence of the PG, 10 −8 to 10 −4 M, on longitudinal tissue strips from the same segments was also examined. The in vitro results demonstrate that PGF 2α has only a weak contractile effect on duodenal and jejunal strips. This effect was enhanced in the presence of atropine and indomethacin. In the in vivo part of the study PGF 2α induced an inhibition of antral electrical activity as evidenced by a prolongation of the inhibitory phases and a reduction of the frequency of the fast oscillations. In the small intestine only ileal activity was changed significantly. PGF 2α provoked an increase in the phase II or irregular spiking activity and an increase in the interval of the migrating myoelectrical complexes in this segment.

Effect of infusion of a diarrheogenic dose of PGE 2 on gastrointestinal electrical activity in the conscious piglet

In 5 conscious piglets with electrodes implanted on the antrum pylori and small intestine, phasic and integrated electrical activity was daily recorded. PGE 2, 10 μg/kg/min, was infused intravenously during 1.5 h and the induced changes in electrical activity were analyzed. Clinical appearance was also studied. PGE 2 induced an inhibition in both antral and intestinal activity. In the antrum this inhibition was characterized by a decrease in the frequency of electrical control activity and fast oscillations, and an increase in the duration of the inhibitory phase. Small intestinal recordings revealed an increase in the quiescence phase for the duodenum and a decrease in the integrated total activity for the duodenum, jejunum and ileum, induced by a decrease in phase II activity. PGE 2 was without influence on phase III activity and the recycling of the migrating myoelectrical complexes. All piglets developed a severe diarrhea. Vomiting, sedation, fever and shivering were observed in most animals. These data suggest that the diarrheogenic effect of PGE 2 is not provoked by an increase in small intestinal motility. Moreover, the direct effect of this PG is a partial inhibition of gastrointestinal electrical activity.

Influence of indomethacin on endotoxin-induced changes in gastrointestinal myoelectrical activity and some haematological and clinical parameters in the conscious piglet.

The effect of indomethacin, administered intravenously at 5 mg/kg, on the changes in gastrointestinal myoelectrical activity, rectal body temperature, clinical appearance and some haematological parameters induced by intravenous bolus injection of endotoxin, at 10 micrograms/kg, was examined in conscious piglets with electrodes implanted in the antrum pylori, duodenum, jejunum and ileum. Indomethacin inhibited the endotoxin-induced febrile response and the accompanying clinical signs. However, it was without influence on the induced leukopenia and shift to the left. Indomethacin both delayed the onset of and shortened the endotoxin-induced increase in the duration of the antral inhibitory phase and the duodenal phase I activity. It therefore appears that prostanoids are probably not the main factors involved in the endotoxin-induced haematological and gastrointestinal myoelectrical activity changes in the piglet.

Effect of the GABAA agonist muscimol on prolactin secretion from human prolactin-secreting adenomas and GH3 rat pituitary tumour cells.

The effect of muscimol, a specific potent GABAA receptor agonist, on prolactin release from human prolactin-secreting tissue was investigated using a perifusion system. Perifusion studies on normal rat anterior pituitary tissue, which has identical GABA receptors to those found in normal human pituitary glands, show that muscimol has a specific biphasic effect on prolactin release. This is characterized by an initial transient stimulation (222.3 +/- 21.6% of basal) lasting for 5-10 min followed by a more prolonged inhibitory phase (63.9 +/- 3.1% inhibition of basal). Five human prolactin-secreting adenomas were studied, and in none of the tumours could a biphasic response be demonstrated. One of the prolactin-secreting adenomas had a blunted inhibitory response, but the other 4 showed no inhibitory effect of muscimol on prolactin release. Muscimol had no significant effect on basal or thyrotropin-releasing-hormone (TRH)-stimulated prolactin secretion from GH3 rat pituitary tumour cells. These studies suggest that the GABAergic effect on prolactin secretion is absent or altered in both rat and human prolactin-secreting tumour cells.

Three types of inhibitory postsynaptic potentials generated by interneurons in the anterior thalamic complex of cat.

1. These experiments were carried out to study how thalamic interneurons generate inhibitory postsynaptic potentials (IPSPs) in relay cells. Intracellular recordings were performed in the anterior thalamic (AT) nuclei, a nuclear group in which interneurons constitute the only intrathalamic source of gamma-aminobutyric acid (GABA). 2. In the AT complex, as in most dorsal thalamic nuclei, interneurons can influence relay cells through their presynaptic dendrites (PSDs) and their axons. This dual mode of action is paralleled by a different termination pattern of prethalamic fibers and cortical axons on interneurons. Prethalamic fibers, which in the AT nuclei arise in the mammillary bodies (MBs), end mostly on PSDs, whereas cortical terminals usually synapse on the parent dendrites of PSDs. We therefore took advantage of the differential mode of termination of cortical and MB afferents on interneurons to infer the respective roles of the axons and PSDs of interneurons in the genesis of the IPSPs recorded from relay cells. 3. In all responsive AT cells, cortical stimuli delivered at low frequency (less than or equal to 0.5 Hz) evoked a biphasic IPSP, with an early and a late phase, having a total duration of 221.96 +/- 8.18 ms (mean +/- SE). The early part of the IPSP (termed A) had a reversal potential (ER) close to the equilibrium potential for Cl- ions: -79.25 +/- 2.14 mV. Furthermore, it reversed in polarity after impalement of the cells with KCl-filled pipettes. The late IPSP (termed B) always began before the end of the early IPSP, 45.93 +/- 2.50 ms after the onset of the A-IPSP. The B-IPSP had an ER of -109 +/- 2.4 mV and was not affected by Cl- injection. 4. By contrast, MB stimuli delivered at low frequency (less than or equal to 0.5 Hz) evoked a triphasic IPSP having a total duration of 220.5 +/- 9.42 ms in most (61.2%) AT cells. The IPSP with the shortest latency (termed a) was evoked only by MB stimuli. Before the return of the membrane potential to the resting level, a second hyperpolarizing potential began (7.41 +/- 0.46 ms after the onset of the a-IPSP). This second inhibitory phase was biphasic and had electrophysiological characteristics similar to the biphasic A- and B-IPSP evoked by cortical stimulation. Both the MB-evoked a- and A-IPSPs had an ER close to the equilibrium potential for Cl- ions (-72.22 +/- 0.68 and -72 +/- 0.82 mV, respectively) and reversed in polarity after impalement of the cells with KCl-filled pipettes.(ABSTRACT TRUNCATED AT 400 WORDS)

Excitatory synaptic potentials in kainic acid-denervated rat CA1 pyramidal neurons

Intracellular recordings were performed in the CA1 region of the rat hippocampus following an ipsilateral intraventricular injection of kainic acid. Seven days postlesion, graded bursts of up to four action potentials could be evoked by stimulation of the stratum radiatum. The evoked EPSPs underlying these bursts showed a prolonged 10-90% rise time and half-width compared to control EPSPs, an absence of a significant inhibitory phase, and an increase in magnitude and duration at depolarized resting levels. The evoked EPSPs also exhibited a significant decrease in amplitude and time course in response to D-APV (D-2-amino-5-phosphonovaleric acid; 1-20 microM), though this effect was variable from cell to cell. The prolonged time course, voltage sensitivity, and response to a selective NMDA antagonist confirmed that the major component of the EPSP in neurons from lesioned slices was mediated by NMDA receptors. The partial denervation of the CA1 area induced by the kainic acid led to both an enhanced NMDA-mediated excitatory phase and a decrease in postsynaptic inhibition, resulting in the pronounced hyperexcitability noted in the lesioned slices.

Differential synaptic effects on physiological flexor hindlimb motoneurons from cutaneous nerve inputs in spinal cat

1. We previously demonstrated in the spinal cat that superficial peroneal cutaneous nerve stimulation produced strong reflex contraction in tibialis anterior (TA) and semitendinosus (St) muscles but unexpectedly produced mixed effects in another physiological flexor muscle, extensor digitorum longus (EDL). The goal of the present study was to further characterize the organization of ipsilateral cutaneous reflexes by examining the postsynaptic potentials (PSPs) produced in St, TA, and EDL motoneurons by superficial peroneal and saphenous nerve stimulation in decerebrate, spinal cats. 2. In TA and St motoneurons, low-intensity cutaneous nerve stimulation that activated only large (A alpha) fibers [i.e., approximately 2-3 times threshold (T)], typically produced biphasic PSPs consisting of an initial excitatory phase and subsequent inhibitory phase (EPSP, IPSP). Increasing the stimulus intensity to activate both large (A alpha) and small (A delta) myelinated cutaneous fibers supramaximally (15-45 T) tended to enhance later excitatory components in TA and St motoneurons. 3. In EDL motoneurons, 2-3 T stimulation of the superficial peroneal nerve evoked initial inhibition (of variable magnitude) in 7/10 EDL motoneurons tested, with either excitation (n = 2) or mixed effects (n = 1) observed in the remaining EDL motoneurons. Saphenous nerve stimuli produced excitation either alone, or preceded by an inhibitory phase in EDL. Increasing the stimulus intensity enhanced later inhibitory influences from superficial peroneal and excitatory influences both from superficial peroneal and saphenous nerve inputs in EDL motoneurons. 4. Short-latency (less than 1.8 ms) EPSPs were observed in a few motoneurons in all reflex pathways examined, except for EPSPs in EDL motoneurons evoked by saphenous stimulation. IPSPs with central latencies less than 1.8 ms were also produced by both saphenous (TA, n = 1; EDL, n = 2) and superficial peroneal (EDL, n = 4) nerve stimulation. 5. The results, in comparison with other reports employing spinal and nonspinal preparations, suggest that removal of influences from higher centers reveals inhibitory circuits from the superficial peroneal and saphenous nerves to EDL motoneurons in the spinal preparation. The inhibitory inputs observed are thought to reflect the activation of "specialized" reflex pathways. Additionally, the demonstration of short-latency EPSPs and IPSPs suggest that the minimal linkage in both the excitatory and inhibitory cutaneous reflex pathways examined is disynaptic. The results are discussed in relation to previous studies on classically conditioned flexion reflex facilitation in spinal cat.

The masseteric reflex evoked by tooth and denture tapping

The characteristics of the masseter reflex evoked by tapping a maxillary incisor were compared with the reflex pattern evoked by tapping a corresponding denture tooth after insertion of an immediate denture. Up to three inhibitory phases (I-1, I-2 and I-3), followed by excitation, were found on an averaged EMG. The tapping force threshold for the early inhibitory phase was lower than for the late phases. The pattern of the reflex was generally the same before and after insertion of the denture, but the threshold values increased. After insertion of the denture, the threshold for I-1 increased from 1 +/- 0.3N to 2.2 +/- 0.4N, the threshold for I-2 increased from 2.4 +/- 0.8N to 3.8 +/- 0.9N, and the threshold for I-3 increased from 5.1 +/- 0.6N to 8.3 +/- 0.9N. The latency period for I-1 also increased from 12.3 +/- 0.5 ms to 13.1 +/- 0.3 ms after insertion of the denture. After relining, the threshold for evoking I-1 decreased from 2.7 +/- 1.2N to 1.2 +/- 0.6N. It was assumed that the mechanoreceptors situated in the mucosa under the denture base could take over the functional role of the periodontal mechanoreceptors for evoking the masseter reflex during tapping, and that these afferents probably had connections to the same interneurones.