Hypersensitivity pneumonitis in rabbits. Modulation of pulmonary inflammation by long-term aerosol challenge with antigen

Immunized rabbits that were aerosol challenged for 2 to 3 wk with pigeon dropping extract, an etiologic agent of hypersensitivity pneumonitis, developed chronic pulmonary inflammation associated with cell-mediated immunity in bronchoalveolar cells. However, prolonged aerosol challenge for 12 wk resulted in the diminution of pulmonary inflammation (modulation) and the loss of demonstrable cell-mediated immunity. This was probably not due to loss of sensitized lymphocytes that mediated pulmonary inflammation. Furthermore, rabbits undergoing modulation when they were challenged with an unrelated antigen were refractory to the development of pulmonary inflammation for at least 9 wk. After this refractory period, animals reimmunized and aerosol challenged with pigeon dropping extract displayed an anamnestic response and produced pulmonary lesions that were strikingly similar to the histopathology of human hypersensitivity pneumonitis.     

Operant conditioning studies of taste discrimination in the pigeon (Columba livia)

In the conditioning procedure employed in this study, pigeons were trained to dip their bills into a container and then to peck either at a left or at a right key, depending on whether the container was full of distilled water or of a solution of the substance being tested. The discrimination thresholds found (from one bird each) were 2 g/l (0.034 M) for NaCl, 2 g/l (0.024 M) for NaHCO₃, 1 g/l (0.013 M) for KCl, 0.5 g/l (0.005 M) for KHCO₃. Following the same procedure, two birds were then faced with the choice between the solution of the known substance and of a novel one. A higher degree of discrimination was found between NaHCO₃ and KHCO₃ than between NaHCO₃ and NaCl; in the latter case, choices appeared to be mostly based on the concentration of the two substances.     

Distribution of serotonin-immunoreactivity in the brain of the pigeon (Columba livia)

The distribution of serotonin (5-HT)-containing perikarya, fibers and terminals in the brain of the pigeon (Columba livia) was investigated, using immunohistochemical and immunofluorescence methods combined with retrograde axonal transport. Twenty-one different groups of 5-HT immunoreactive (IR) cells were identified, 2 of which were localized at the hypothalamic level (periventricular organ, infundibular recess) and 19 at the tegmental-mesencephalic and rhombencephalic levels. Ten of the cell groups were situated within the region of the midline from the isthmic to the posterior rhombencephalic level and constituted the raphe system (nucleus annularis, decussatio brachium conjunctivum, area ventralis, external border of the nucleus interpeduncularis, zona peri-nervus oculomotorius, zona perifasciculus longitudinalis medialis, zona inter-flm, nucleus linearis caudalis, nucleus raphe superior pars ventralis, nucleus raphe inferior). The 9 other cell populations belonged to the lateral group and extended from the posterior mesencephalic tegmentum to the caudal rhombencephalon [formatio reticularis mesencephali, nucleus ventrolateralis tegmenti, ectopic area (Ec) of the nucleus isthmo-opticus (NIO), nucleus subceruleus, nucleus ceruleus, nucleus reticularis pontis caudalis, nucleus vestibularis medialis, nucleus reticularis parvocellularis and nucleus reticularis magnocellularis]. Combining the retrograde axonal transport of rhodamine -isothiocyanate (RITC) after intraocular injection and immunohistofluorescence (fluoresceine isothiocyanate: FITC/5-HT) showed the centrifugal neurons (NIO, ec) to be immunonegative. Serotonin-IR fibers and terminals were found to be very broadly distributed within the brain and were particularly prominent in several structures of the telencephalon (archistriatum pars dorsalis, nucleus taeniae, area parahippocampalis, septum), diencephalon (nuclei preopticus medianus, magnocellularis, nucleus geniculatus lateralis pars ventralis, nucleus triangularis, nucleus pretectalis), mesencephalon-rhombencephalon (superficial layers of the optic tectum, nucleus ectomamillaris, nucleus isthmo-opticus and in most of the cranial nerve nuclei). Comparing the present results with those of previous studies in birds suggests some major serotonin containing pathways in the avian brain and clarifies the possible origin of the serotonin innervation of some parts of the brain. Moreover, comparing our results in birds with those obtained in other vertebrate species shows that the organization of the serotoninergic system in many regions of the avian brain is much like that found in reptiles and mammals.Abbreviations Ad Archistriatum pars dorsalis - alp area interpeduncularis - al ansa lenticularis - Ann nucleus annularis - APH area parahippocampalis - Av archistriatum pars ventralis - AVT area ventralis (Tsai) - bcd brachium conjunctivum descendens - BO bulbus olfactorius - ca commisssura anterior - CDL area corticoidea dorsolateralis - Cer cerebellum - cf fiber layer of the olfactory bulb - cg granular cell layer of the olfactory bulb - co chiasma opticum - ct commissura tectalis - dbc decussatio brachiorum conjunctivorum - DL nucleus dorsolateralis anterior thalami - DLP nucleus dorsolateralis posterior thalami - DM nucleus dorsomedialis thalami - dnt decussatio nervi trochlearis - E ectostriatum - Ec ectopic area of the nucleus isthmo-opticus - EM nucleus ectomamillaris - flm fasciculus longitudinalis medialis - fpl fasciculus prosencephali lateralis - FRL formatio reticularis lateralis mesencephali - FRM formatio reticularis medialis mesencephali - fu fasciculus uncinatus - GCt substantia grisea centralis - GLv nucleus geniculatus lateralis pars ventralis - gr granular cell layer of the cerebellum - HA hyperstriatum accessorium - HD hyperstriatum dorsale - HIS hyperstriatum intercalatus superior - HL nucleus habenularis lateralis - HM nucleus habenularis medialis - Hp hippocampus - HV hyperstriatum ventrale - ICo nucleus intercollicularis - i-flm inter fasciculus longitudinalis medialis - Imc nucleus ishmi pars magnocellularis - Ip nucleus interpeduncularis - Ipc nucleus isthmi pars parvocellularis - LA nucleus lateralis anterior thalami - La nucleus laminaris - LC nucleus linearis caudalis - LHy nucleus lateralis hypothalami - lm lemniscus medialis - LoC locus coeruleus - LPO lobus paraolfactorius - ls lemniscus spinalis - MLd nucleus mesencephalicus lateralis pars dorsalis - mo molecular layer of the cerebellum - MoV nucleus motorius nervi trigemini - Mp magnocellularis preopticus - N neostriatum - NIII nucleus nervi oculomotorii - nIII nervus oculomotorius - NIV nucleus nervi trochlearis - NV nucleus nervi trigemini nV nervus trigeminus - NVII nucleus nervifacialis - nVIII nervus octavus - NIO nucleus isthmo-opticus - om tractus occipitomesencephalicus - OPH hypothalamic periventricular organ - Os nucleus olivaris superior - Ov nucleus ovoidalis - PA paleostriatum augmentatum - Po nucleus pontis - POM nucleus preoticus medialis - PP paleostriatum primitivum - PrV nucleus sensorius principalis nervi trigemini - PT nucleus pretectalis - pu Purkinje cell layer - qf tractus quintofrontalis - Rai nucleus raphe inferior - RasV nucleus raphe superior pars ventralis - ReI recessus infundibularis - Rm nucleus reticularis magnocellularis - Rp nucleus reticularis parvocellularis - RPc nucleus reticularis pontis caudalis - RPO nucleus reticularis pontis oralis - Rt nucleus rotundus - Ru nucleus ruber - S septum - Sac stratum album centrale - SCH stratum cellulare hypothalami - Sgc stratum griseum centrale - Sgf stratum griseum et fibrosum superficiale - Sgfp stratum griseum et fibrosum periventriculare - Sop stratum opticum - SP nucleus subpretectalis - SPC nucleus superficialis parvocellularis - Spl nucleus spiriformis lateralis - Spm nucleus spiriformis medialis - SRt nucleus subrotundus - SuC nucleus subcoeruleus - to tractus opticus - Tn nucleus taeniae - TPc nucleus tegmenti pedunculo-pontinus pars compacta - Tr nucleus triangularis - tsm tractus septomesencephalicus - ttd nucleus et tractus descendens nervi trigemini - Tu nucleus tuberis - Vel nucleus vestibularis lateralis - Vem nucleus vestibularis medialis - Vlt nucleus ventrolateralis thalami - VT nucleus ventrolateralis tegmenti - Zp-flm zona perifasciculus longitudinalis medialis - Zp-NIII zona perinervus oculomotorius     

Cell populations of the ganglion cell layer: displaced amacrine and matching amacrine cells in the pigeon retina

Summary The proportion and size distribution of ganglion and non-ganglion cells in the ganglion cell layer of different areas of the pigeon retina was examined in whole-mounts of the retina by retrograde axonal transport of horseradish peroxidase (HRP) from large brain injections. A maximum of 98% of cells were labelled in the red field and a maximum of 77% in the peripheral yellow field. Unlabelled cell bodies were 30% smaller than labelled ganglion cells and had a mean diameter of 6.2 m and a size range of 4 to 9 m. The morphology of cells in the ganglion cell layer was examined by Golgi staining of retinal whole-mounts. Small glia, displaced amacrine and ganglion cells were found. Displaced amacrine cell bodies were about 30% smaller than ganglion cells and their size distribution was similar to the unlabelled cells in HRP preparations. Displaced amacrine cells had small rounded cell bodies (mean diameter 6.2 m) increasing in size with eccentricity, and a unistratified dendritic tree of fine, nearly radial, varicose dendrites in sublamina 4 of the inner plexiform layer. They had elliptical dendritic fields (mean diameter 66 m) aligned parallel to the retina's horizontal meridian. A population of amacrine cells was found with somas at the inner margin of the inner nuclear layer and soma and dendritic morphology matching those of displaced amacrines. These amacrine cells had unistratified dendritic trees at the junction of sublaminae 1 and 2 of the inner plexiform layer. Pigeon displaced amacrine cells and their matching amacrines are similar to starburst cells of the rabbit retina. They may participate in on and off pathways to ganglion cells and their lamination suggests that they are cholinergic.     

Acute effects of light and darkness on sleep in the pigeon (Columba livia)

In addition to entraining circadian rhythms, light has acute effects on sleep and wakefulness in mammals. To determine whether light and darkness have similar effects in birds, the only non-mammalian group that displays sleep patterns comparable to mammals, we examined the effects of lighting changes on sleep and wakefulness in the pigeon. We quantified sleep behavior (i.e., bilateral or unilateral eye closure) in pigeons maintained under a 12:12 LD cycle, and immediately following a change from a 12:12 to a 3:3 LD cycle. During both LD cycles, sleep was most prevalent during dark periods. During the 3:3 LD cycle, darkness had the greatest sleep promoting effect during the hours corresponding to the subjective night of the preceding 12:12 LD cycle, whereas light suppressed sleep across circadian phases. As previously suggested, the light-induced decrease in sleep in the subjective night might be partly mediated by the suppression of melatonin by light. Although the sleep promoting effect of darkness was modulated by the circadian rhythm, sleep in darkness occurred during all circadian phases, suggesting that darkness per se may play a direct role in inducing sleep. In addition to the effects of lighting on behavioral state, we observed an overall bias toward more right eye closure under all lighting conditions, possibly reflecting a response to the novel testing environment.     

The discriminative stimulus properties of LY233708, a selective serotonin reuptake inhibitor, in the pigeon

Rationale: Understanding the contribution of the various serotonin (5-HT) receptor subtypes to the behavioral effects of selective serotonin reuptake inhibitors (SSRIs) may contribute to the discovery of increasingly effective drugs for the treatment of conditions such as depression, panic and obsessive-compulsive disorders. Objectives: A drug discrimination procedure was used to determine whether the administration of an SSRI was associated with a specific interoceptive stimulus cue and to what extent that cue was related to activation of the 5-HT_1A receptor. Method: Pigeons were trained to discriminate 20 mg/kg of the short acting, SSRI, LY233708 dihydrochloride dihydrate [(–)-cis-1-(6-chloro-1,2,3,4- tetrahydro-1-methyl-2-naphthalenyl)piperazine] from saline. Results: LY233708 induced a specific, dose-related stimulus cue. The SSRIs, fluoxetine and citalopram, induced dose-related responding on the LY233708-associated key. In contrast, nisoxetine, a selective norepinephrine uptake inhibitor, induced responding on the saline-associated key. The prototypical 5-HT_1A agonist, 8-OH-DPAT [8-hydroxy-(2-di-n-propylamino)tetralin] substituted for LY233708. This generalization was blocked by the selective 5-HT_1A antagonist, WAY-100635 [N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridinyl) cyclohexanecarboxamide]. Conclusion: These data demonstrate that an SSRI can induce a specific, stable discriminative stimulus that appears to involve activation of the 5-HT_1A receptor in the pigeon. Received: 11 January 1999 / Final version: 7 May 1999     

Effects of chronic Δ9-tetrahyrocannabinol administration on schedule-controlled behavior of pigeons: Cross-tolerance to pentobarbital and barbital

Pigeons responding under a variable-interval (VI) 75-s schedule of food presentation were used to study cross-tolerance from ⁹-tetrahyrocannabinol (⁹-THC) to pentobarbital and barbital. After initial dose-effect functions for pentobarbital and barbital were determined, the birds received ⁹-THC injections for 6 weeks. This chronic administration regimen resulted in a greater than 100-fold tolerance to ⁹-THC. Redetermination of the pentobarbital and barbital dose-effect functions during the chronic ⁹-THC regimen revealed statistically significant shifts to the right for the pentobarbital (0.191 log unit) and barbital (0.078 log unit) dose-effect curves. All six birds showed tolerance to pentobarbital, while four of the six showed tolerance to barbital. Blood barbital levels before and after chronic ⁹-THC administration did not differ significantly. Tolerance to ⁹-THC was more prolonged and of much greater magnitude than the cross-tolerance to pentobarbital or barbital. The results demonstrate that cross-tolerance can develop from ⁹-THC to a barbiturate that normally undergoes little metabolism.     

Hair cell loss and regeneration after severe acoustic overstimulation in the adult pigeon

The extent of hair cell regeneration following acoustic overstimulation severe enough to destroy tall hair cells, was determined in adult pigeons. BrdU (5-bromo-2′-deoxyuridine) was used as a proliferation marker. Recovery of hearing thresholds in each individual animal was measured over a period of up to 16 weeks after trauma. In ears with loss of both short and tall hair cells, little or no functional recovery occurred. In ears with less damage, where significant functional recovery did occur, there were always a few rows of surviving hair cells left at the neural edge of the basilar papilla. In the region of hair cell loss, numerous BrdU labeled cells were found. However, only a small minority of these cells were regenerated hair cells, the majority being monolayer cells. Irrespective of the extent of the region of hair cell loss, regenerated hair cells were observed predominantly in a narrow strip at the transition from the abneural area of total hair cell loss and the neural area of hair cell survival. With increasing damage this strip moved progressively towards the neural edge of the papilla. No regeneration of hair cells was observed in the abneural region of total hair cell loss, even up to 16 weeks after trauma. The results indicate that there is a gradient in the destructive effect of loud sound across the width of the basilar papilla, from most detrimental at the abneural edge to least detrimental at the neural edge. Both tall and short hair cells can regenerate after sound trauma. Whether they do regenerate or not depends on the degree of damage to the area of the papilla where they normally reside. Regeneration of new hair cells occurs only in a narrow longitudinal band, which moves from abneural into the neural direction with increasing damage. In the area neural to this band, hair cells survive the overstimulation. In the area abneural to this band, sound damage is so severe, that no regeneration of hair cells occurs. As a consequence morphological and functional deficits persist.     

Quantitative immunogold evidence that glutamate is a neurotransmitter in afferent synaptic terminals within the isthmo-optic nucleus of the pigeon centrifugal visual system

A quantitative electron microscopic analysis of glutamate (GLU) immunoreactivity using the post-embedding immunogold technique was carried out within the isthmo-optic nucleus (ION) of the pigeon centrifugal visual system (CVS). Measurements were performed in each of eight different categories of axon terminals, including those that were GABA-immunoreactive (-ir), considered representing control profiles and identified using a single or double-label immunocytochemical procedure. The results demonstrated that the glutamate immunogold particle densities for both mitochondrial and vesicular pools and for total surface area of bouton profiles were significantly higher in P1a, P1b and P2b terminals and not significantly different in P4 and P5 terminals compared to those recorded in control GABA-ir terminals (P2a, P2c, P3). Moreover, the values measured in GLU-ir positive profiles were all significantly higher than in either P4 or P5 terminals. The results suggest that tectal neurons, which provide the main input to the ION cells, are either inhibitory GABA-ir possibly associated with P2c and/or P3 terminals or excitatory GLU-ir via P1a, P1b and P2b terminals. Such differential effects of tectal afferents may be the basis for the modulation of centrifugal activity and consequently of end target retinal ganglion cell responses. The data are relevant to hypotheses implicating the avian CVS in mechanisms of selective enhancement of visual attention to either novel or meaningful stimuli within the visual field.     

Feature detection of visual neurons in the nucleus of the basal optic root in pigeons

Previous studies have shown that the nucleus of the basal optic root in birds is involved in optokinetic nystagmus, and its neurons respond not only to large-field stimuli but also to a single object moving through their excitatory receptive fields. The present study provides electrophysiological evidence that basal optic neurons in pigeons respond vigorously to motion of a black leading edge. The orientation of the edge is also an essential factor affecting visual responses of these cells, showing that any deviation of the edge from the direction perpendicular to the preferred direction decreases visual responses in most cases. Furthermore, visual responses increase as the edge is lengthened within the excitatory receptive field. However, a square, semicircle and isosceles with an area ratio of 1.00: 0.39: 0.50 but with an identical leading edge elicit almost the same responses, which are not dependent on the shape and area of visual stimuli. It suggests that these feature extraction properties, similar to those of neurons in the nucleus lentiformis mesencephali, may be specialized for detecting optokinetic stimuli rich in luminance contrasts, but not for realizing pattern recognition.