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Biomedical subjects

J T Schmidt

Publications and source records attributed to J T Schmidt.

At least 19 recordsLinked to original sources
PubMed2005

Risk factors of frequent exacerbations in difficult-to-treat asthma.

Recurrent exacerbations are a major cause of morbidity and medical expenditure in patients with asthma. Various exogenous and endogenous factors are thought to influence the level of asthma control, but systematical data on the involvement of these factors in the recurrence of asthma exacerbations are scarce. In this study, 13 clinical and environmental factors potentially associated with recurrent exacerbations were investigated in 136 patients with difficult-to-treat asthma. Patients with more than three severe exacerbations (n = 39) in the previous year were compared with those with only one exacerbation per year (n = 24). A systematic diagnostic protocol was used to assess 13 potential risk factors. Factors significantly associated with frequent exacerbations included: severe nasal sinus disease (adjusted odds ratio (OR) 3.7); gastro-oesophageal reflux (OR 4.9); recurrent respiratory infections (OR 6.9); psychological dysfunctioning (OR 10.8); and obstructive sleep apnoea (OR 3.4). Severe chronic sinus disease and psychological dysfunctioning were the only independently associated factors (adjusted OR 5.5 and 11.7, respectively). All patients with frequent exacerbations exhibited at least one of these five factors, whilst 52% showed three or more factors. In conclusion, the results show that recurrent exacerbations in asthma are associated with specific co-morbid factors that are easy to detect and that are treatable. Therapeutic interventions aimed at correcting these factors are likely to reduce morbidity and medical expenditure in these patients.

Adolescent↗
PubMed2000

MK801 increases retinotectal arbor size in developing zebrafish without affecting kinetics of branch elimination and addition.

Visual activity refines the retinotopic map formed on tectum during regeneration and development in goldfish through an N-methyl-D-aspartate (NMDA) receptor-mediated mechanism. Retinal arbors are enlarged in fish with unrefined maps. Here, we examined the effect of NMDA receptor blockers on the development of retinotectal arbors in zebrafish. Since visual behaviors begin 68-79 h postfertilization, we blocked NMDA receptors by immersion of larvae in MK801, AP5, or CPP starting at either 48 or 72 h. We then labeled axons with DiI at 72 or 96 h and examined them 5-9 h later. Arbors at 101-105 h (31 cases) were larger than at 77-79 h (11 cases): The average number of branches increased from 4.0 to 7.6 and the area (convex polygon method) increased by 42%. Blocking NMDA receptors with MK801 from 72 to 101-105 h significantly enlarged arbor size, but the number of branches remained roughly the same. The length and area of the arbors were both significantly increased (21% and 36%), whereas the width increased by a smaller amount (6%). This increase was reflected in longer distances between branches within the arbor (interbranch segments, +13%) as well as in the summed length of all branches (+28%). This selective effect on the extent but not number of branches is in agreement with our previous report of strobe effects in both developing and regenerating projections in goldfish, and supports the role of NMDA receptors in the first 24 h of synaptic transmission. We also used DiO to label arbors in time-lapse images taken at hourly intervals from 77 to 112 h. These sequences confirmed that individual arbors grew during this time, but showed that rates of branch addition and deletion and branch lifetimes were unaltered by the MK801 treatment. This is consistent with a simple model of random insertion of new branches and selective activity-driven elimination of those at the periphery to keep the normal arbor focused. Blocking NMDA receptors is postulated to randomize the elimination allowing the periphery to expand, thus accounting for the enlarged areas, without change in branch numbers or branch dynamics.

2-Amino-5-phosphonovalerate↗
PubMed1999

Adenosine A1 and class II metabotropic glutamate receptors mediate shared presynaptic inhibition of retinotectal transmission.

Presynaptic inhibition is one of the major control mechanisms in the CNS. Previously we reported that adenosine A1 receptors mediate presynaptic inhibition at the retinotectal synapse of goldfish. Here we extend these findings to metabotropic glutamate receptors (mGluRs) and report that presynaptic inhibition produced by both A1 adenosine receptors and group II mGluRs is due to G(i) protein coupling to inhibition of N-type calcium channels in the retinal ganglion cells. Adenosine (100 microM) and an A1 (but not A2) receptor agonist reduced calcium current (I(Ca2+)) by 16-19% in cultured retinal ganglion cells, consistent with their inhibition of retinotectal synaptic transmission (-30% amplitude of field potentials). The general metabotropic glutamate receptor (mGluR) agonist 1S,3R-1-amino-cyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD, 50 microM) and the selective group II mGluR receptor agonist (2S, 2'R,3'R)-2-(2',3'-dicarboxy-cyclopropyl)glycine (DCG-IV, 300 nM) inhibited both synaptic transmission and I(Ca2+), whereas the group III mGluR agonist L-2-amino-4-phosphono-butyrate (L-AP4) inhibited neither synaptic transmission nor I(Ca2+). When the N-type calcium channels were blocked with omega-conotoxin GVIA, both adenosine and DCG-IV had much smaller percentage effects on the residual 20% of I(Ca2+), suggesting effects mainly on the N-type calcium channels. The inhibitory effects of A1 adenosine receptors and mGluRs were both blocked by pertussis toxin, indicating that they are mediated by either G(i) or G(o). They were also inhibited by activation of protein kinase C (PKC), which is known to phosphorylate and inhibit G(i). Finally, when applied sequentially, inhibition by adenosine and DCG-IV were not additive but occluded each other. Together these results suggest that adenosine A1 receptors and group II mGluRs mediate presynaptic inhibition of retinotectal synaptic transmission by sharing a pertussis toxin (PTX)-sensitive, PKC-regulated G(i) protein coupled to N-type calcium channels.

Adenosine↗
PubMed1998

Up-regulation of protein kinase C in regenerating optic nerve fibers of goldfish: immunohistochemistry and kinase activity assay.

Protein kinase C (PKC) activation has been associated with synaptic plasticity in many projections, and manipulating PKC in the retinotectal projection strongly affects the activity-driven sharpening of the retinotopic map. This study examined levels of PKC in the regenerating retinotectal projection via immunostaining and assay of activity. A polyclonal antibody to the conserved C2 (Ca2+ binding) domain of classical PKC isozymes (anti-panPKC) recognized a single band at 79-80 kD on Western blots of goldfish brain. It stained one class of retinal bipolar cells and the ganglion cells in normal retina, as shown previously. Strong staining was not present in the optic fiber layer of retina or in optic nerve, optic tract, or terminal zone in tectum, with the exception of a single fascicle of optic nerve fibers that by their location and by L1 (E587) staining were identified as those arising from newly added ganglion cells at the retinal margin. Normal tectal sections showed dark staining of a subclass of type XIV neuron with somas at the top of the periventricular layer and an apical dendrite ascending to stratum opticum. In regenerating retina, swollen ganglion cells stained darkly and stained axons were seen in the optic fiber layer. In regenerating optic nerve (2-11 weeks postcrush), all fascicles of optic fibers stained darkly for both PKC and L1(E587). At 5 weeks postcrush, PKC staining could also be seen in the medial and lateral optic tracts and stratum opticum at the front half of the tectum and very lightly over the terminal zones. PKC activity was measured in homogenized tissues dissected from a series of fish with unilateral nerve crush from 1 to 5 weeks previously. Activity levels stimulated by phorbols and Ca2+ were measured by phosphorylation of a specific peptide and referred to levels measured in the opposite control side. Regeneration did not increase overall PKC activity in retina or tectum, but in optic nerve there was an 80% rise after the first week. The increased activity verifies that the increased staining in nerve represented an up-regulation of functional PKC during nerve regeneration.

Animals↗
PubMed1998

Role for cell adhesion and glycosyl (HNK-1 and oligomannoside) recognition in the sharpening of the regenerating retinotectal projection in goldfish.

Cell-adhesion molecules (CAMs) are thought to play crucial roles in development and plasticity in the nervous system. This study tested for a role for cell adhesion and in particular, the recognition of two glycosyl epitopes (HNK-1 and oligomannoside) in the activity-driven sharpening of the retinotopic map formed by the regenerating retinal fibers of goldfish. HNK-1 is a prominent glycosyl epitope on many CAMs and extracellular matrix (ECM) molecules, including NCAM, L1, ependymin, and integrins, which have all been implicated in synaptic plasticity. To test for a role of HNK-1 in the sharpening process, we used osmotic minipumps to infuse HNK-1 antibodies for 7-21 days into the tectal ventricle starting at 18 days after optic nerve crush. Retinotopic maps recorded at 76-86 days postcrush showed a lack of sharpening similar to that seen previously with two antibodies to ependymin, an HNK-1-positive ECM component present in cerebrospinal fluid. The multiunit receptive fields at each point averaged 26 degrees versus 11-12 degrees in regenerates infused with control antibodies or Ringer's alone. The HNK-1 epitope also binds to the G2 domain of laminin to mediate neuron-ECM adhesion. To test for a role for laminin, a polyclonal antibody was similarly infused and also prevented sharpening to approximately the same degree. The results support a role for the HNK-1 epitope and laminin in retinotectal sharpening. The oligomannoside epitope (recognized by monoclonal antibody L3) on the CAM L1 interacts with NCAM on the same cell to promote stronger L1 homophilic interactions between cells. Both an L1-like molecule and NCAM are prominently reexpressed in the regenerating retinotectal system of fish. Infusion of oligomannosidic glycopeptides resulted in decreased sharpening, with multiunit receptive fields that averaged 22.7 degrees. Infusions of mannose-poor glycopeptides less prominently disrupted sharpening, with average multiunit receptive fields of 18 degrees. Thus, oligomannosidic glycans in particular may play a role in retinotopic sharpening. Blocking glycan-mediated interactions between CAMs and ECM molecules could decrease the extent of exploratory growth of retinal axon collaterals, preventing them from finding their retinotopic sites, or could interfere with L1 or NCAM and laminin binding at the synaptic densities preventing stabilization of retinotopically appropriate synapses. Together, these results support a prominent role for cell adhesion and glycan epitopes in visual synaptic plasticity.

Animals↗
PubMed1998

Adenosine A1 receptors mediate retinotectal presynaptic inhibition: uncoupling by C-kinase and role in LTP during regeneration.

Presynaptic adenosine receptors inhibit transmitter release at many synapses and are known to exist on retinotectal terminals. In this paper we show that adenosine decreases retinotectal field potentials by approximately 30% and investigate the mechanism. First, as judged by the effects of specific calcium channel blockers, retinotectal transmission was mediated almost exclusively by N-type calcium channels, which are known to be modulated by adenosine A1 receptors. Transmission was completely blocked by either omega-Conotoxin GVIA (-100%, N-type blocker) or omega-Conotoxin MVIIC (-99%, N-, P- and Q-type blocker) and was not significantly affected by omega-Agatoxin IVA [+1.7 +/- 9. 3% (SE), P-,Q-type blocker], but was augmented slightly by nifedipine(+9.3 +/- 2.1%, L-type blocker). Second, the adenosine inhibition was presynaptic, as indicated by a 43% increase in paired-pulse facilitation. Third, the selective A1 agonist cyclohexyl adenosine (CHA) at 50 nM caused a 21% decrease in amplitude and the selective A2 agonist N6-[2-(3, 5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA) at 100 nM caused a 24% increase. Fourth, the selective A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) alone produced an increase in the field potential, suggesting a tonic inhibition mediated by endogenous adenosine. Fifth, pertussis toxin eliminated adenosine inhibition implicating Gi or Go protein coupling. Sixth, C-kinase activation eliminated the A1-mediated inhibition. In regenerating projections, adenosine also caused a decrease in transmission (-30 +/- 12%), but after induction of long-term potentiation (LTP) via trains of stimuli or via treatment with the phosphatase inhibitor okadaic acid, the adenosine response was converted to an augmentation. Because LTP is associated with C-kinase activation, this is consistent with C-kinase uncoupling the A1 receptor from inhibiting N-type Ca2+ channels. This uncovers the A2-mediated augmentation as demonstrated in normals with DPMA. Such an effect could account in part for the LTP of immature synapses and the change from rapidly fatiguing to robust synaptic transmission.

Adenosine↗
PubMed1996

Rapid activity-dependent sprouting of optic fibers into a local area denervated by application of beta-bungarotoxin in goldfish tectum.

The retinotectal projection is known to be capable of extensive long-term expansion of connections, but it is not known how fast such changes can occur or what triggers sprouting of terminals. We studied sprouting of optic fibers into an area denervated by local microinjection of beta-bungarotoxin (beta-BTX), a specific presynaptic neurotoxin with phospholipase A2 activity that destroys nerve terminals at the neuromuscular junction. After injection of 0.1 pmol of beta-BTX, the optic terminals fired spontaneously with decreasing amplitude and became silent within 1 to 2 h. Outside the injection zone, the retinotectal map was normal, so the silent zone was associated with a scotoma in the visual field. Horseradish peroxidase (HRP) staining of the entire optic nerve showed a denervated region at the injection site with beaded, degenerating fibers at its edge. Between 3 and 9 days later, optic units were recorded within the injection zone whose receptive fields lay just outside the scotoma in the visual field, indicating that intact surrounding terminals had sprouted into the area. These sprouts made functional connections, as indicated by field potential recordings and current source-density analysis. At this time, HRP staining also demonstrated retinal innervation within the injection zone. By 12 days, normal maps with no scotoma were recorded and HRP staining was normal at the injection site, indicating that the beta-BTX-damaged fibers had regenerated to reclaim their tectal sites. The results show that the retinotectal projection of goldfish is very dynamic, since intact optic fibers can sprout into adjacent vacant postsynaptic territory within 2 to 3 days, much faster than previously reported. In a final experiment, we showed that this sprouting is activity-dependent, since it could be prevented by blocking retinal activity with intraocular tetrodotoxin (TTX) during the first 2 days postinjection, even though TTX block of activity does not block regeneration in this system. One possible mechanism for this rapidly triggered sprouting is that arachidonic acid liberated by beta-BTX acts as a sprouting factor to attract surrounding healthy fibers into the denervated region but requires activity at the terminals to be effective.

Animals↗
PubMed1996

Myosin light chain kinase: expression in neurons and upregulation during axon regeneration.

Myosin light-chain kinase (MLCK) regulates actin-myosin II interactions in nonskeletal muscle cells, and the use of specific pharmacological inhibitors has implicated MLCK in retinal growth cone motility and neurite outgrowth. To further establish the existence and functions of MLCK in neurons, we isolated cDNAs encoding two forms of goldfish MLCK that were differentially expressed in the brain and gut and we sequenced the form most abundantly expressed in the brain (GFMLCK1). In situ hybridization with a cRNA probe specific to GFMLCK1 revealed widespread expression in CNS neurons, including tectal periventricular neurons and cerebellar and medullary neurons. After optic nerve crush, expression was markedly increased in the retinal ganglion cells. Expression peaked during the phase of axonal outgrowth, which, when taken together with our previous pharmacological studies, further supports a role for MLCK in growth cone motility.

Amino Acid Sequence↗
PubMed1995

[Life-threatening angioedema as a side effect of angiotensin-converting-enzyme (ACE) inhibitors].

During the past years, angioedema occurring in association with angiotensin converting enzyme (ACE) inhibitors is seen more and more often. This is due to the increasing use of these drugs for hypertension and congestive heart failure. If the diagnosis is missed and prescription of the ACE inhibitor is prolonged, recurrent and more severe episodes of angioedema may occur. In case of involvement of the upper airway and respiratory distress, the condition may be life-threatening. We demonstrate three such patients, men of 84, 73 and 63 years old. First of all, the airway should be secured. Administration of epinephrine may be indicated. Further use of ACE inhibitors is contraindicated.

Aged↗
PubMed1994

C-kinase manipulations disrupt activity-driven retinotopic sharpening in regenerating goldfish retinotectal projection.

Regenerating optic axons initially branch over a wide area in tectum to form a crude retinotopic map. The map is sharpened, and retinotopically appropriate synapses are stabilized via NMDA receptors that detect, via summation of EPSPs, the coincident activity of neighboring ganglion cells that make synapses onto common tectal cells. Sharpening shares a number of properties with long-term potentiation (LTP) in hippocampus. This study tested whether protein kinase C (PKC) activation is necessary for sharpening as it is for LTP. Intraocular (IO) or intracranial (IC) injections of kinase inhibitors or activators were made every other day from 19 to 37 days postcrush (sensitive period), and the projections formed were later recorded. Retinotopic sharpening was prevented by IC injection of the following agents: (1) general kinase inhibitors sphingosine and H7 (100-200 microM in fluid above brain), (2) active but not inactive phorbols (TPA, 1 microM), and (3) calphostin C (1 microM), a specific and irreversible PKC inhibitor. The mature projection on the opposite tectum, however, when examined was not unsharpened. Lack of sharpening was reflected in multiunit fields at each tectal point that averaged 27 degrees-30 degrees versus 11 degrees in Ringers and inactive phorbol control regenerates. Intraocular injections of either TPA (1 microM), or calphostin C (1 microM) also prevented sharpening (26 degrees and 32 degrees multiunit fields), suggesting action on PKC axonally transported to the presynaptic terminals. Calphostin C had no noticeable effect on the firing patterns of retinal ganglion cells. The endogenous activator of PKC, arachidonic acid (AA), disrupted sharpening at 20 microM or higher (IC injection, 32 degrees multiunit fields), while a control fatty acid, elaidic acid, had no effect. Although AA at 5 microM showed no effect, and diacylglycerol at 5 microM exhibited only small effects, together they produced a large synergistic effect (32 degrees multiunit fields). Such synergy mirrors the synergy in the activation of several isoforms of PKC. Actual concentrations in the extradural fluid around the brain were assayed via injections of 3H-AA. Levels fell about sixfold after a day and by an additional fivefold the second day before the next injection. The results confirm that activity-driven retinotopic sharpening is very sensitive to manipulations of kinases, especially PKC.

Animals↗
PubMed1994

Kinase requirement for retinal growth cone motility.

Since cytoplasmic Ca2+ levels are reported to regulate neurite elongation, we tested whether calcium-activated kinases might be necessary for growth cone motility and neurite elongation in explant cultures of goldfish retina. Kinase inhibitors and activators were locally applied by micropipette to retinal growth cones and the responses were observed via phase-contrast videomicroscopy. In some cases, growth rates were also quantified over several hours after general application in the medium. The selective inhibitors of protein kinase C, calphostin C (0.1-1 microM) and chelerythrin (up to 50 microM), caused no obvious changes in growth cones or neurite elongation, and activators of PKC (phorbols, arachidonic acid, and diacylglycerol) also were generally without effects, although phorbols slowed the growth rate. Inhibitors of protein kinase A and tyrosine kinases also produced no obvious effects. The calmodulin antagonists, calmidazolium (0.1 microM), trifluoperazine (100 microM), and CGS9343B (50 microM), however, caused a reversible growth cone arrest with loss of filopodia and lamellipodia. The growth cone became a club-shaped swelling which sometimes moved a short distance back the shaft, leaving evacuated filaments at points of strong filopodial attachments. A similar reversible growth cone arrest occurred with the general kinase inhibitors: H7 at 200 but not at 100 microM, and staurosporine at 100 but not 10 nM, suggesting possible involvement of a calmodulin-dependent kinase (camK) rather than PKC. The selective inhibitor of camKII, KN-62 (tested up to 50 microM), produced no effects, but the specific myosin light-chain kinase (MLCK) inhibitors ML-7 (3-5 microM) and ML-9 (5-10 microM) reversibly reproduced the effect, suggesting that MLCK rather than camKII is necessary for growth cone motility. The MLCK inhibitors' effects both on growth cone morphology and on F-actin filaments (rhodamine-phalloidin staining) were similar to those caused by cytochalasin D (5 microM), and are discussed in light of findings that inhibiting MLCK disrupts actin filaments in astrocytes and fibroblasts.

Actins↗
PubMed1993

Activity-driven sharpening of the retinotectal projection in goldfish: development under stroboscopic illumination prevents sharpening.

Blocking or synchronizing activity during regeneration of the retinotectal projection prevents both the sharpening of the retinotopic map recorded on tectum and the refinement of the structure of individual arbors within the plane of the map, and this refinement is triggered by N-methyl-D-aspartate (NMDA) receptors. We tested whether activity-driven refinement also occurs during development of the projection in larval and young adult goldfish. Shortly after hatching, larval goldfish were placed into tanks within light-tight chambers illuminated by a xenon strobe at 1 Hz for 14 h of each daily cycle. Fish were reared for 1.5-2 years, until large enough to record in our retinotectal mapping apparatus (6 cm length). Age- and size-matched controls had normal maps with multiunit receptive fields (MURFs) recorded at each tectal point of 10.8 degrees (0.16 S.E.M., n = 5), whereas the strobe-reared fish had only roughly retinotopic maps with much enlarged MURFs averaging 26.7 degrees (1.41 S.E.M., n = 5). This enlargement represents an abnormal convergence onto each tectal point, as the maps failed to sharpen during development. The arbors of individual retinal axons were stained with horseradish peroxidase (HRP) in larval fish and in adult strobe-reared and control fish. They were drawn with camera lucida from tectal whole mounts, and analyzed for spatial extent in the plane of the retinotopic map, order of branching, number of branch endings, depth of termination, and caliber of the parent axon. Arbors from larval fish (1-2 weeks) were small (approximately 50 x 40 microns) with less than 10 branches, occupied a single strata, and could not be separated into different classes by caliber of axon. The 87 arbors stained in control adult fish (6 cm long) were much like previously examined adult arbors, with those from fine, medium, and coarse axons averaging 115, 166, and 194 microns in extent, respectively, and having 17-24 branch endings. The 110 arbors from 12 strobe-reared fish were often abnormal. Although the fasciculation was normal, the extrafascicular routes were abnormal with reversing turns. The axons often had branches along their course, and these branches were scattered across a wider extent, rather than forming a distinct cluster. In contrast, neither the number of branches nor the depths of termination was significantly changed in any group. The coarse caliber arbors were most abnormal, being 64% longer and 30% wider than controls. The fine caliber arbors were also significantly larger by about 20%, but the medium caliber arbors were not enlarged.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Ependymin as a substrate for outgrowth of axons from cultured explants of goldfish retina.

Ependymin, a prominent protein of the brain's extracellular fluid (ECF) was previously implicated in the consolidation of memory and in the activity-driven sharpening of the retinotectal projection. Because both these phenomena probably involve the growth and elaboration of appropriate synapses, we have tested whether ependymin can serve as a substrate for the growth of axons from goldfish retinal ganglion cells in a culture assay. Ependymin (Ep), laminin (LAM), polylysine (PL), and Concanavalin A (Con A) were plated on glass coverslips either uniformly or in striped patterns. Ep alone, either soluble or partly polymerized (by dropping calcium concentration and pH), was a good substrate for axonal outgrowth, as good or better than PL and Con A, but not as good as LAM. Neurites grew faster on LAM (71 microns/h) than on Ep (32 microns/h) or on PL (22 microns/h). Fasciculation was low on LAM, intermediate on Ep, and highest on PL. In exclusive side-by-side stripe assays, axons preferred LAM over Ep, but gave weak or no preference for Ep over Con A or PL. With stripes of LAM + Ep alongside pure LAM, the axons preferred the mixture of LAM + Ep. When antibodies to Ep were plated in stripes over continuous Ep substrate, the axons avoided the antibody-blocked stripes and grew on the Ep stripes. Antibodies to Ep did not, however, block growth on laminin substrates, nor did antibodies to LAM block growth on Ep. Dot blots and western blots showed very little cross recognition between the antibodies. Ependymin is a good substrate for neurite outgrowth, which is normally present in ECF, and adhesion to Ep is independent of LAM and possibly additive to it.

Animals↗
PubMed1991

The long latency component of retinotectal transmission: enhancement by stimulation of nucleus isthmi or tectobulbar tract and block by nicotinic cholinergic antagonists.

The optic tectum of teleosts contains high concentrations of nicotinic and muscarinic acetylcholine receptors and receives putative cholinergic innervation from both nucleus isthmi in the tegmentum and a population of intrinsic tectal cells. Using in vitro preparations of goldfish brain, we have examined the effects of cholinergic antagonists and stimulation of nucleus isthmi on the tectal response to optic nerve stimulation. Our results show that: (1) a long latency component of the retinotectal field potential is polysynaptic in origin and occurs in isolated tectum; (2) this component can spread across the tectum from a beam of stimulated fibers and can appear in areas where the monosynaptic response is small or absent; (3) both monosynaptic and long latency components of the field potential are enhanced by prior stimulation of nucleus isthmi or the tectobulbar tract (15-300 ms); (4) both the long latency component of the field potential and the effects of stimulation of nucleus isthmic or tectobulbar tract are blocked by low concentrations of nicotinic antagonists; and (5) in deeper tectum a second polysynaptic response uncovered by pharmacological block of inhibition is not blocked by nicotinic antagonists. These results indicate that the cholinergic neurons intrinsic to tectum have a role in the spread of retinotectal excitation by nicotinic actions, and that stimulation of nucleus isthmi or tectobulbar tract facilitates activity in this system. There is in addition a separate recurrent excitatory circuit in tectum.

Alcuronium↗