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PubMed2003

Exposing ferrets to cigarette smoke and a pharmacological dose of beta-carotene supplementation enhance in vitro retinoic acid catabolism in lungs via induction of cytochrome P450 enzymes.

In our previous studies, we found lower levels of retinoic acid (RA) in the lungs of ferrets exposed to cigarette smoke and/or a pharmacological dose of beta-carotene. To determine whether this is involved in excessive catabolism of RA via cytochrome P450 (CYP) induction, we carried out in vitro incubations of RA with the lung microsomal fractions of ferrets with or without CYP inhibitors and antibodies against CYP. The polar metabolites (4-oxo-RA and 18-hydroxy-RA) of RA metabolism after the incubation were analyzed by HPLC. Expressions of CYP (1A1, 1A2, 2E1 and 3A1) were examined using Western blot analysis. Incubation of various concentrations of RA with the lung microsomal fraction from ferrets exposed to cigarette smoke, a pharmacological dose of beta-carotene or their combination dose-dependently increased the levels of 4-oxo-RA and 18-hydroxy-RA compared with that of the control ferrets. At all RA concentrations, this increase was the greatest in lung tissue from the combined treatment group. Furthermore, this enhanced RA catabolism was substantially (approximately 80%) inhibited by nonspecific CYP inhibitors (disulfiram and liarozole), but was partially (approximately 50%) inhibited by resveratrol (CYP1A1 inhibitor), alpha-naphthoflavone (CYP1A2 inhibitor) and antibodies against CYP1A1 and CYP1A2. Cigarette smoke exposure and/or pharmacological doses of beta-carotene increased levels of CYP1A1 and 1A2 by three- to sixfold but not levels of 2E1 and 3A1 in ferret lung tissue. These findings suggest that low levels of RA in the lung of ferrets exposed to cigarette smoke and/or pharmacological doses of beta-carotene may be caused by the enhanced RA catabolism via induction of CYP, CYP1A1 and CYP1A2 in particular, which provides a possible explanation for enhanced lung carcinogenesis seen with pharmacological doses of beta-carotene supplementation in cigarette smokers.

Analysis of Variance↗
PubMed1983

Steroid metabolism in the corpus luteum of the ferret.

Implantation in the ferret is believed to be induced by a luteal substance which acts in concert with progesterone (P4) and which is secreted sometime between Days 6 and 8 of pregnancy. This experiment was designed to identify the steroid products synthesized by ferret corpora lutea (CL) on these 2 days of pregnancy. CL were dissected from ferrets on Day 6 or 8 of pregnancy and incubated with [3H] pregnenolone (P3), [3H] P4, or [3H] dehydroepiandrosterone (DHEA). Controls with no tissue or with 50 microliters packed blood cells were incubated at the same time. After incubation of Day 6 CL with [3H] P3 for 180 min, 39% of the added label was found incorporated into P4, 3% into 17 alpha-hydroxyprogesterone (17 alpha-OHP4) and 1% into androstenedione (A). Incubation of Day 8 CL with the same precursor resulted in 35%, 1% and 0.65% of the label being incorporated into the previously mentioned products, respectively. Incubations of Days 6 and 8 ferret CL with [3H] P4 or [3H] DHEA confirmed these results, demonstrating activity of C21-steroid, 17 alpha-hydroxylase and delta 5-isomerase, 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). These results suggest that ferret CL primarily accumulate steroids of the delta4 pathway on both Days 6 and 8 of pregnancy, with P4, 17 alpha-OHP4, A and testosterone (T) being the most abundant products after in vitro incubation. Thus, ferret CL appear to metabolize steroids in a manner similar to that observed in rats, sows and mares.

17-Hydroxysteroid Dehydrogenases↗
PubMed1985

Coital stimuli controlling luteinizing hormone secretion and ovulation in the female ferret.

A series of experiments focused on the masculine coital behaviors controlling pituitary luteinizing hormone (LH) secretion and reflex ovulation in the estrous female ferret. An initial experiment investigated which coital stimuli from the male are required to induce ovulation. It was found that corpus luteum formation, which served as an index of ovulation, occurred in estrous female ferrets only if the male achieved a penile intromission. Neck gripping, mounting, and pelvic thrusting behavior without intromission by the male failed to induce ovulation. A second experiment investigated the timing and magnitude of the coitus-induced LH surge associated with ovulation. Blood was obtained via jugular catheters from estrous females in various mating situations. Plasma LH concentrations were measured by a heterologous radioimmunoassay that was validated for use in the ferret. A significant surge in plasma LH occurred only when an intromission was achieved by the stud male. Plasma LH was significantly elevated 2.0 h after the introduction of the male, peak values were reached 6.0 h later, and this elevation lasted on average 5.7 hours (5/5 females). No LH rise occurred in 2/2 female ferrets in which only neck gripping, mounting, and pelvic thrusting, but no intromission, were allowed to occur. The ferret mating pattern and the resultant LH response differ from those seen in three other induced ovulators (cat, vole, and rabbit) in which the male's intromission latency and duration are much shorter than in the ferret, and in which a distinctive peak in plasma LH often occurs within 1 h after mating.

Animals↗
PubMed1993

Luteal protein secretion during preimplantation in the ferret.

Ferret CL were collected on Days 5-11 of pregnancy or pseudopregnancy and incubated in McCoy's medium with radiolabeled amino acids to determine the ability of ferret CL to synthesize and secrete proteins during the preimplantation period. Products recovered from the medium were separated by one- and two-dimensional SDS-PAGE followed by fluorography and were quantified by densitometry. Selected secretory proteins were tentatively identified with specific antibodies on Western blots. Ferret CL synthesized and secreted a relatively large number of radiolabeled products. The predominant secretory proteins had molecular masses of 16, 22, 28, 32, 47, 68, and 185 kDa and were secreted at all stages of the preimplantation period. There were no qualitative changes in ferret luteal protein synthesis and secretion between Days 5-11 of pregnancy, and neither ovine prolactin (oPRL) nor dibutyryl cAMP (dcAMP) affected the pattern of protein secretion. However, oPRL (100 and 1000 ng/ml) increased incorporation of radiolabeled amino acids into luteal proteins during a 36-h incubation. The relative mobility of a 185-kDa radiolabeled product was identical to that of alpha 2-macroglobulin (alpha 2M) subunits. Antibody to human alpha 2M cross-reacted with a product (185 kDa) in ferret luteal extracts and culture medium, and the partially purified protein (185 kDa) inhibited trypsin activity. The major radiolabeled secretory protein (32 kDa) exhibited weak cross-reaction with antibody to a human tissue inhibitor of metalloproteinase (TIMP). This study demonstrates the wide range of proteinaceous secretory products of the ferret CL, two of which have been tentatively identified as protease inhibitors.

Animals↗
PubMed1995

Patterns of melatonin secretion during sexual maturation in female ferrets.

These studies were an examination of the changes in function of the pineal gland and its secretory product, melatonin, during sexual maturation induced by stimulatory photoperiod in ferrets. Plasma melatonin patterns were determined for 48-h intervals in ferrets undergoing photoperiod-stimulated sexual maturation. Sampling regimens were conducted when ferrets were 10, 15, 16, and 23 wk of age. Clear daily rhythms in melatonin concentrations were apparent in ferrets as young as 10 wk of age. Melatonin secretion increased with the onset of darkness each day and fell with lights-on the next morning. When the photoperiod was changed from a short day (8L:16D) to a long day (16L:8D) at 15 wk of age, the melatonin rise did not contract immediately to the shorter dark phase for at least the first two nights. By 1 wk after imposition of the new, long-day photoperiod, however, the pattern of melatonin concentrations in plasma was synchronized to the new photoperiod. These studies show that ferrets can detect photoperiod at a much younger age than that at which they can respond to long days with accelerated maturation and further, that while the pineal gland mediates the photoperiod-induced maturation of ferrets, other factors are involved in the 5-6-wk interval between the onset of long days and the maturational response of the hypothalamo-hypophyseal-gonadal axis in this species.

Aging↗
PubMed2002

Conditions for in vitro maturation and artificial activation of ferret oocytes.

The ferret represents an attractive species for animal modeling of lung diseases because of the similarity between ferret and human lung biology and its relatively small size and short gestation time. In an effort to establish experimental protocols necessary for cloning ferrets, optimized conditions for in vitro maturation and artificial activation of ferret oocytes were examined. Cumulus-oocyte complexes were harvested from ovaries of superovulated ferrets, and in vitro maturation was evaluated in three different culture media: medium 1 (TCM-199 + 10% FBS), medium 2 (TCM-199 + 10% FBS with eCG [10 IU/ml] and hCG [5 IU/ml]), or medium 3 (TCM-199 + 10% FBS with eCG, hCG, and 17beta-estradiol [2 microg/ml]). After 24 h of maturation in vitro, the maturation rate of oocytes cultured in medium 2 (70%, n = 79) was significantly greater (P < 0.01) than those of oocytes cultured in the other two media (27%-36%, n = 67-73). At 48 h, similar maturation rates (56%-69%, n = 76-87) were observed for all three types of media. For activation experiments, oocytes cultured in medium 2 were stimulated with electrical and chemical stimuli either individually or in combination. Treatment with cycloheximide and 6-dimethylaminopurine (6-DMAP) following electrical stimulation resulted in 43% (n = 58) of the oocytes developing to the blastocyst stage. Such an activation rate represented a significant improvement over those obtainable under other tested conditions, including individual treatment with electrical pulses (10%, n = 41), cycloheximide (3%, n = 58), or 6-DMAP (5%, n = 59). Blastocysts derived from in vitro activation appeared to be normal morphologically and were composed of an appropriate number of both inner cell mass (mean +/- SEM, 10.3 +/- 1.1; n = 11) and trophectoderm (60.8 +/- 2.9, n = 11) cells. These results have begun to elucidate parameters important for animal modeling and cloning with ferrets.

Animals↗
PubMed1979

Comparisons of virulence of influenza virus recombinants in ferrets in relation to their behaviour in man and their genetic constitution.

Two parent viruses, A/Finland/4/74(H3N2) and A/Okuda/57(H2N2), virulent and attenuated respectively for man, showed similar differences of virulence in ferrets as judged by estimations of 50% minimal infectious doses (MID50), the level and persistence of nasal infection, the height and duration of pyrexia and the level of lung infection. In ferrets, two recombinant clones, WRL 94(H3N2) and WRL 105(H3N2), were almost as virulent as A/Finland and indistinguishable from one another, a result which agreed well with genetic analysis (Hay et al. 1977); the RNA pieces of these recombinants appeared identical and largely derived from the virulent parent (A/Finland). The results in ferrets did not agree with tests on clone WRL 94 in small numbers of human volunteers but they were not inconsistent with those on clone WRL 105 in larger numbers. It is possible therefore that careful tests in ferrets may yield more accurate information on the virulence of strains than limited tests in human volunteers. A rapid test for virulence in ferrets is described. It could be used to screen many additional recombinants thereby yielding information on the genetical basis of virulence and indicating possible vaccine strains for more thorough testing in ferrets and in man.

Animals↗
PubMed1983

Drug effects on afterdischarge and seizure threshold in lissencephalic ferrets: an epilepsy model for drug evaluation.

In normal and lissencephalic ferrets with chronically implanted electrodes, two antiepileptic drugs, (E)-2-[(amino)phenylmethylen]-benzo [b] thiophen-3(2H)-on (AF-CX 921 XX) and carbamazepine (CBZ), were compared. The variables included afterdischarges (AD) and seizures induced by cortical electrical stimulations (ES). Both drugs were given orally, 100 mg/kg of pure substance. ES was applied before and 1, 2, 3, 4, 5, and 24 h after drug administration. Lissencephaly was produced by a single intraperitoneal injection of 15 mg methylazoxymethanol acetate to pregnant animals. The administration of both drugs resulted in increases of the AD threshold current to 240% in the normal and to 170% in the lissencephalic ferrets, in comparison with control stimulations (the difference significant at p less than 0.001). Moreover, duration of the AD was shorter (p less than 0.01) than before the drugs. Seizure threshold also increased 170% after AF-CX 921 XX and 175% after CBZ in normal and 153% and 138% in lissencephalic ferrets, respectively. The difference between the two drugs was significant. However, in contrast to the threshold, duration of seizures during AF-CX 921 XX administration was significantly shorter (p less than 0.05) than during CBZ. In general, lissencephalic ferrets responded less than normal ferrets to both drugs, but AF-CX 921 XX had a greater inhibitory effect on the duration of seizures. The lissencephalic ferret is proposed as an animal model of epilepsy with diffuse developmental defects.

Animals↗
PubMed1994

Relaxation in ferret ventricular myocytes: unusual interplay among calcium transport systems.

Transport systems responsible for removing Ca2+ from the myoplasm during relaxation in isolated ferret ventricular myocytes were studied using caffeine-induced contractures. Internal calcium concentration ([Ca2+]i) was measured with the fluorescent calcium indicator indo-1, and the results were compared with our recent detailed characterizations in rabbit and rat myocytes. Relaxation and [Ca2+]i decline during a twitch in ferret myocytes were fast and similar to that in rat myocytes (i.e. half-time, t 1/2 approximately 100-160 ms). During a caffeine-induced contracture (SR Ca2+ accumulation prevented), relaxation was still relatively fast (t 1/2 = 0.57 s) and similar to relaxation in rabbit supported mainly by a strong Na(+)-Ca2+ exchange. When both the SR Ca2+ uptake and Na(+)-Ca2+ exchange are blocked (by caffeine and 0 Na+, 0 Ca2+ solution) relaxation in the ferret myocyte is remarkably fast (approximately 5-fold) compared with rabbit and rat myocytes. The decline of the Cai2+ transient was also fast under these conditions. These values were similar to those in rat under conditions where relaxation is due primarily to Na(+)-Ca2+ exchange. Additional inhibition of either the sarcolemmal Ca(2+)-ATPase or mitochondrial Ca2+ uptake caused only modest slowing of the relaxation of caffeine-induced contracture in 0 Na+, 0 Ca2+ (t 1/2 increased to approximately 3 s). In rabbit myocytes the relaxation t 1/2 is slowed to 20-30 s by these procedures. Even when the systems responsible for slow relaxation in rabbit ventricular myocytes are inhibited (i.e. sarcolemmal Ca(2+)-ATPase and mitochondrial Ca2+ uptake) along with the SR Ca(2+)-ATPase and Na(+)-Ca2+ exchange, relaxation and [Ca2+]i decline in ferret myocytes remain rapid compared with rabbit myocytes. Ca2+ taken up by mitochondria in rabbit myocytes during a caffeine contracture in 0 Na+, 0 Ca2+ solution gradually returns to the SR after caffeine removal, but this component appears to be much smaller in ferret myocytes under the same conditions. We tested for possible residual Ca2+ transport by each of the four systems which suffice to explain Ca2+ removal from the cytoplasm in rabbit (SR Ca(2+)-ATPase, Na(+)-Ca2+ exchange, sarcolemmal Ca(2+)-ATPase and mitochondrial Ca2+ uptake). We conclude that there is an additional calcium transport system at work in ferret myocytes. For this additional system, our results are most compatible with a trans-sarcolemmal Ca2+ transport, but neither a cation exchanger nor a Ca(2+)-ATPase with characteristics like that in other cardiac cells. This additional system appears able to transport Ca2+ nearly as fast as the Na(+)-Ca2+ exchange in rat ventricular myocytes.

Animals↗
PubMed2005

Modulation of gastro-oesophageal vagal afferents by galanin in mouse and ferret.

The neuropeptide galanin is found in the central and peripheral nervous systems. It may have excitatory or inhibitory actions via three subtypes of G-protein-coupled receptor, and it modulates the mechanosensitivity of somatic sensory fibres. We aimed to determine if galanin also modulates vagal afferent mechanosensitivity, and to localize endogenous sources. The responses of ferret and mouse gastro-oesophageal vagal afferents to graded mechanical stimuli were investigated in vitro. The effects of galanin and/or the galanin receptor antagonist galantide on these responses were quantified. Immunohistochemistry for galanin was performed in ferret and mouse proximal stomach and nodose ganglion. In ferrets, retrograde labelling of gastric afferents to the nodose ganglion was combined with immunohistochemistry. When exposed to galanin (1-10 nM), 18/31 ferret and 12/15 mouse gastro-oesophageal afferents (tension, mucosal and tension/mucosal receptors) showed inhibition of mechanosensitivity. Four of 31 ferret afferents showed potentiation of mechanosensitivity, and 9/31 were unaffected (2/15 and 1/15 in mouse, respectively). Galanin effects were reversed after washout or by galantide (10-30 nM). Galantide given alone increased mechanosensitivity. Galanin immunoreactivity was found in nodose neurones, including those innervating the stomach in ferret. Enteric neurones were also galanin immunoreactive, as were endings associated with myenteric ganglia and smooth muscle. We conclude that galanin potently modulates mechanosensitivity of gastro-oesophageal vagal afferents with either facilitatory or inhibitory actions on individual afferent fibres. Both intrinsic and extrinsic (vagal) neurones contain galanin and are therefore potential sources of endogenous galanin.

Afferent Pathways↗
PubMed1983

Presence of oligoclonal immunoglobulin G bands and lack of matrix protein antibodies in cerebrospinal fluids and sera of ferrets with measles virus encephalitis.

Young adult ferrets were immunized with measles vaccine and 5 to 6 weeks later inoculated intracerebrally with Vero cells persistently infected with cell-associated strain D.R. of measles virus isolated from a patient with subacute sclerosing panencephalitis. Of nine ferrets which survived the infection for 3 weeks or longer, five showed neurological signs. At the time of death they had widespread inflammation in their brains, and cell-associated virus was isolated from three ferrets sacrificed from 5 weeks to 7 months after inoculation. Four ferrets did not develop clinical signs, but two of these had mild inflammation in the brain 7 months and 2 1/2 years after inoculation, respectively. Cerebrospinal fluids drawn by cisternal puncture from infected ferrets at the time of sacrifice had neutralizing titers against measles virus similar to the titers found in sera, but antibody against the measles virus matrix protein was not detectable. Cerebrospinal fluid showed increased immunoglobulin G (IgG) and had distinct measles virus-specific oligoclonal IgG bands. The intensity of the bands correlated with the neutralizing titers of the fluids. These results confirm and extend earlier findings and indicate that persistent measles virus infection in ferrets is similar to human subacute sclerosing panencephalitis and can be used to study certain aspects of persistent brain infections leading to subacute encephalitis.

Animals↗
PubMed1993

Pneumocystis carinii organisms obtained from rats, ferrets, and mice are antigenically different.

Pneumocystis carinii infections were developed in animals immunosuppressed by dexamethasone treatment either from activation of latent infection (ferret) or by transtracheal inoculation with P. carinii-infected lung tissue from the homologous species (rat or mouse). Convalescent-phase antisera were obtained by stopping dexamethasone treatment after 2 to 4 weeks and allowing animals 5 to 8 weeks for recovery. P. carinii harvests from infected lungs were purified by differential filtration, solubilized in buffer containing urea, sodium dodecyl sulfate (SDS), and 2-mercaptoethanol, subjected to SDS-polyacrylamide gel electrophoresis, and blotted to polyvinylidene difluoride sheets for Western immunoblot analysis. These lung preparations are hereafter referred to as P. carinii antigens. Convalescent-phase antisera from each animal species were reacted on Western blots of P. carinii antigens prepared from organisms isolated from rats, ferrets, or mice. Each combination of P. carinii antigens and antisera from the same species of animal reacted with three or more P. carinii antigen proteins. Convalescent-phase mouse antisera reacted with P. carinii antigens from mice but not rats or ferrets. Convalescent-phase rat antisera reacted with P. carinii antigens from rats and mice but not ferrets, and convalescent-phase ferret antisera showed reactions with ferret and mouse P. carinii antigens but not rat antigens. These findings indicate antigenic differences among P. carinii strains infecting these animals.

Animals↗
PubMed1997

Canine distemper virus (CDV) infection of ferrets as a model for testing Morbillivirus vaccine strategies: NYVAC- and ALVAC-based CDV recombinants protect against symptomatic infection.

Canine distemper virus (CDV) infection of ferrets causes an acute systemic disease involving multiple organ systems, including the respiratory tract, lymphoid system, and central nervous system (CNS). We have tested candidate CDV vaccines incorporating the fusion (F) and hemagglutinin (HA) proteins in the highly attenuated NYVAC strain of vaccinia virus and in the ALVAC strain of canarypox virus, which does not productively replicate in mammalian hosts. Juvenile ferrets were vaccinated twice with these constructs, or with an attenuated live-virus vaccine, while controls received saline or the NYVAC and ALVAC vectors expressing rabies virus glycoprotein. Control animals did not develop neutralizing antibody and succumbed to distemper after developing fever, weight loss, leukocytopenia, decreased activity, conjunctivitis, an erythematous rash typical of distemper, CNS signs, and viremia in peripheral blood mononuclear cells (as measured by reverse transcription-PCR). All three CDV vaccines elicited neutralizing titers of at least 1:96. All vaccinated ferrets survived, and none developed viremia. Both recombinant vaccines also protected against the development of symptomatic distemper. However, ferrets receiving the live-virus vaccine lost weight, became lymphocytopenic, and developed the erythematous rash typical of CDV. These data show that ferrets are an excellent model for evaluating the ability of CDV vaccines to protect against symptomatic infection. Because the pathogenesis and clinical course of CDV infection of ferrets is quite similar to that of other Morbillivirus infections, including measles, this model will be useful in testing new candidate Morbillivirus vaccines.

Animals↗
PubMed1989

Tissue-specific isoform regulation of Na+-K+-ATPase by thyroid hormone in ferrets.

We have shown previously that in the ferret heart there are two isoforms of Na+-K+-ATPase, alpha(+) and alpha, and that these isoforms undergo developmental changes. In the present study, we examine regulation of the isoenzymes by thyroid hormone, which is well known to increase activity of Na+-K+-ATPase in different tissue preparations. Ferrets were injected with L-thyroxine (T4) (0.5 mg/kg, sc) for 3 wk. The T4-treated ferrets gained 58 +/- 32 g body wt compared with 366 +/- 24 g for the control ferrets. Plasma 3,5,3'-triiodothyronine concentrations of the T4-treated animals increased about eightfold 16-18 h after the last injection. The number of alpha(+)- and alpha-subunits in heart homogenates estimated by [3H]ouabain binding was 3.5 +/- 0.1 and 2.5 +/- 0.1 pmol/mg protein, respectively [alpha(+)/alpha = 1.40]. In the T4-treated ferrets, there was no significant increase of the alpha(+)-isoform (3.2 +/- 0.2 pmol/mg protein), whereas the number of alpha-isoform increased significantly to 4.1 +/- 0.3 pmol/mg protein [alpha(+)/alpha = 0.78]. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of partially purified cardiac plasma membrane preparations reveals similar pattern of changes of the isoenzymes. In the kidney, however, there was no significant change in the number of alpha-isoform, which is the predominant isoform in the kidney, and T4 does not appear to induce synthesis of alpha(+)-isoform in the kidney. It is concluded that thyroid hormone induces both isoform- and tissue-specific regulation of the Na+-K+-ATPase alpha-subunits in the ferret. These specific regulations of the isoforms seem to suggest important physiological roles of the isoenzymes.

Animals↗
PubMed1993

Plasticity of autonomic control of emesis in irradiated ferrets.

To investigate the plasticity of the emetic response to irradiation, five groups of ferrets (with the appropriate controls) had either the vagal or the splanchnic nerves transected and either were immediately irradiated under urethan anesthesia or were irradiated in a conscious state at 0.5-4, 4-9, and 24 h and 7 days after nerve transection. All the ferrets used in this study had the left carotid artery and the right jugular vein catheterized several hours before irradiation so that blood pressures could be monitored. In ferrets that were irradiated while anesthetized, bilateral abdominal vagotomy performed immediately before 6-Gy irradiation prevented emesis. Acute bilateral abdominal splanchnicectomy markedly reduced emesis in such cases but had no statistically significant effect in conscious ferrets. The incidence of emesis in conscious controls laparotomized 0.5-4 h before irradiation was 50% after 2 Gy and 100% after 6 Gy. Intact conscious controls were tested with 10 Gy only and showed a 100% incidence of emesis after this dose. Bilateral abdominal vagotomy, performed on ferrets 4-9 h before 8-Gy irradiation of conscious animals, markedly reduced the incidence of radiation-induced emesis. When performed 24 h before irradiation, it abolished emesis. In contrast, vagotomy was ineffective when performed 7 days before irradiation. The data suggest that, after 2-8 Gy, the vagi are the major emetic pathway in conscious ferrets and the splanchnic nerves may, under certain conditions, constitute second or alternate pathways.

Animals↗
PubMed1997

Response properties of neurons in the inferior colliculus of the monaurally deafened ferret to acoustic stimulation of the intact ear.

Response properties of neurons in the central nucleus of the inferior colliculus (ICC) were investigated after unilateral cochlear removal at various ages during infancy. Nineteen ferrets had the right cochlea surgically ablated, either in adulthood or on postnatal day (P) 5, 25, or 40, 3-18 mo before recording. Adult ablations were made on the same day as ("acute," n = 3), or 2-3 mo before ("chronic," n = 3), recording. Two ferrets were left binaurally intact. Single-unit (n = 702) and multiunit (n = 1,819) recordings were made in the ICC of barbiturate-anesthetized ferrets ipsilateral (all ages) or contralateral (P5 and acute adult only) to the intact ear. In binaurally intact animals, tonal stimulation of the contralateral ear evoked excitatory activity at the majority (94%) of recording loci, whereas stimulation of the ipsilateral ear evoked activity at only 33% of recording loci. In acutely ablated animals, the majority of contralateral (90%) and ipsilateral (70%) loci were excited by tonal stimulation of the intact ear. In chronically ablated animals, 80-90% of loci were excited by ipsilateral stimulation. Single-unit thresholds were generally higher for low-best frequency (BF) than for high-BF units, and higher in the ipsilateral than in the contralateral ICC. Analysis of covariance showed highly significant differences between all of the ipsilateral and contralateral groups, but no effects of age at ablation or survival time following ablation, other than that the group ablated at P25 had higher mean ipsilateral thresholds than the groups ablated at P5 or, acutely, in adulthood. Cochlear ablation at P5, 25, or 40 resulted in a significant increase in dynamic ranges of ipsilateral ICC unit rate-intensity functions relative to acutely ablated animals. Dynamic ranges of units in the contralateral ICC of P5-ablated ferrets were also significantly increased compared with those of acutely ablated animals. Cochlear ablation at P5, 25, or 40 resulted in a significant increase in single-unit spontaneous discharge rates in the ICC ipsilateral but not contralateral (P5 only) to the intact ear. These data show that unilateral cochlear removal in adult ferrets leads to a rapid and dramatic increase in the proportion of neurons in the ICC ipsilateral to the intact ear that is excited by acoustic stimulation of that ear. In addition, the data confirm that, in ferrets, cochlear removal in infancy leads to a further increase in responsiveness of individual neurons in the ipsilateral ICC. Finally, the data show that responses in the ICC contralateral to the intact ear are largely but not completely unchanged by unilateral cochlear removal.

Acoustic Stimulation↗
PubMed1988

Modulation by the thyroid state of intracellular calcium and contractility in ferret ventricular muscle.

The purpose of this study was to determine whether the cardiac contractile abnormalities induced by hyperthyroidism or hypothyroidism are caused by changes in intracellular Ca2+ handling or by alterations in the distribution of isoenzymes of ventricular myosin. Right ventricular papillary muscles obtained from euthyroid ferrets and ferrets treated with L-thyroxine (hyperthyroid) or methimazole (hypothyroid) were loaded with the calcium indicator aequorin for recording intracellular Ca2+ levels during isometric contraction. In muscles from the hypothyroid ferrets, peak tension was reduced and the duration of contraction prolonged compared to the controls; these changes were associated with a Ca2+ transient of decreased amplitude and prolonged duration. Hyperthyroidism produced opposite changes in the time course of the Ca2+ transient and the associated isometric contraction. Native polyacrylamide gel electrophoresis was performed on myosin extracted from the right ventricular free wall of control and treated ferrets. The hyperthyroid state was associated with new myosin formation as indicated by the appearance of three myosin bands on the pyrophosphate gel. Gels of myosin from hypothyroid and euthyroid ferrets showed a single band that migrated with the slowest of the three bands from the hyperthyroid ferrets. These results suggest that changes in both Ca2+ handling and myosin isoenzymes may contribute to the contractile abnormalities observed in hyperthyroidism. Alterations in intracellular Ca2+ handling alone may account for the contractile changes induced by hypothyroidism.

Animals↗
PubMed2000

An analysis of orientation and ocular dominance patterns in the visual cortex of cats and ferrets.

We report an analysis of orientation and ocular dominance maps that were recorded optically from area 17 of cats and ferrets. Similar to a recent study performed in primates (Obermayer & Blasdel, 1997), we find that 80% (for cats and ferrets) of orientation singularities that are nearest neighbors have opposite sign and that the spatial distribution of singularities deviates from a random distribution of points, because the average distances between nearest neighbors are significantly larger than expected for a random distribution. Orientation maps of normally raised cats and ferrets show approximately the same typical wavelength; however, the density of singularities is higher in ferrets than in cats. Also, we find the well-known overrepresentation of cardinal versus oblique orientations in young ferrets (Chapman & Bonhoeffer, 1998; Coppola, White, Fitzpatrick, & Purves, 1998) but only a weak, not quite significant overrepresentation of cardinal orientations in cats, as has been reported previously (Bonhoeffer & Grinvald, 1993). Orientation and ocular dominance slabs in cats exhibit a tendency of being orthogonal to each other (Hubener, Shoham, Grinvald, & Bonhoeffer, 1997), albeit less pronounced, as has been reported for primates (Obermayer & Blasdel, 1993). In chronic recordings from single animals, a decrease of the singularity density and an increase of the ocular dominance wavelength with age but no change of the orientation wavelengths were found. Orientation maps are compared with two pattern models for orientation preference maps: bandpass-filtered white noise and the field analogy model. Bandpass-filtered white noise predicts sign correlations between orientation singularities, but the correlations are significantly stronger (87% opposite sign pairs) than what we have found in the data. Also, bandpass-filtered noise predicts a deviation of the spatial distribution of singularities from a random dot pattern. The field analogy model can account for the structure of certain local patches but not for the whole orientation map. Differences between the predictions of the field analogy model and experimental data are smaller than what has been reported for primates (Obermayer & Blasdel, 1997), which can be explained by the smaller size of the imaged areas in cats and ferrets.

Algorithms↗