Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention.

IMPORTANCE: Effective cancer prevention is based on accurate molecular diagnosis and results of genetic family screening, genotype-informed risk assessment, and tailored strategies for early diagnosis. The expanding etiology for hereditary pheochromocytomas and paragangliomas has recently included SDHA, TMEM127, MAX, and SDHAF2 as susceptibility genes. Clinical management guidelines for patients with germline mutations in these 4 newly included genes are lacking. OBJECTIVE: To study the clinical spectra and age-related penetrance of individuals with mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes. DESIGN, SETTING, AND PATIENTS: This study analyzed the prospective, longitudinally followed up European-American-Asian Pheochromocytoma-Paraganglioma Registry for prevalence of SDHA, TMEM127, MAX, and SDHAF2 germline mutation carriers from 1993 to 2016. Genetic predictive testing and clinical investigation by imaging from neck to pelvis was offered to mutation-positive registrants and their relatives to clinically characterize the pheochromocytoma/paraganglioma diseases associated with mutations of the 4 new genes. MAIN OUTCOMES AND MEASURES: Prevalence and spectra of germline mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes were assessed. The clinical features of SDHA, TMEM127, MAX, and SDHAF2 disease were characterized. RESULTS: Of 972 unrelated registrants without mutations in the classic pheochromocytoma- and paraganglioma-associated genes (632 female [65.0%] and 340 male [35.0%]; age range, 8-80; mean [SD] age, 41.0 [13.3] years), 58 (6.0%) carried germline mutations of interest, including 29 SDHA, 20 TMEM127, 8 MAX, and 1 SDHAF2. Fifty-three of 58 patients (91%) had familial, multiple, extra-adrenal, and/or malignant tumors and/or were younger than 40 years. Newly uncovered are 7 of 63 (11%) malignant pheochromocytomas and paragangliomas in SDHA and TMEM127 disease. SDHA disease occurred as early as 8 years of age. Extra-adrenal tumors occurred in 28 mutation carriers (48%) and in 23 of 29 SDHA mutation carriers (79%), particularly with head and neck paraganglioma. MAX disease occurred almost exclusively in the adrenal glands with frequently bilateral tumors. Penetrance in the largest subset, SDHA carriers, was 39% at 40 years of age and is statistically different in index patients (45%) vs mutation-carrying relatives (13%; P < .001). CONCLUSIONS AND RELEVANCE: The SDHA, TMEM127, MAX, and SDHAF2 genes may contribute to hereditary pheochromocytoma and paraganglioma. Genetic testing is recommended in patients at clinically high risk if the classic genes are mutation negative. Gene-specific prevention and/or early detection requires regular, systematic whole-body investigation.

Experience with the use of a partial ossicular replacement prosthesis with a ball-and-socket joint between the plate and the shaft.

BACKGROUND: In the further development of alloplastic prostheses for use in middle ear surgery, the Dresden and Cologne University Hospitals, working together with a company, introduced a new partial ossicular replacement prosthesis in 2011. The ball-and-socket joint between the prosthesis and the shaft mimics the natural articulations between the malleus and incus and between the incus and stapes, allowing reaction to movements of the tympanic membrane graft, particularly during the healing process. STUDY DESIGN: Retrospective evaluation METHODS: To reconstruct sound conduction as part of a type III tympanoplasty, partial ossicular replacement prosthesis with a ball-and-socket joint between the plate and the shaft was implanted in 60 patients, with other standard partial ossicular replacement prosthesis implanted in 40 patients and 64 patients. Pure-tone audiometry was carried out, on average, 19 and 213 days after surgery. Results of the partial ossicular replacement prosthesis with a ball-and-socket joint between the plate and the shaft were compared with those of the standard prostheses. RESULTS: Early measurements showed a mean improvement of 3.3 dB in the air-bone gap (ABG) with the partial ossicular replacement prosthesis with a ball-and-socket joint between the plate and the shaft, giving similar results than the standard implants (6.6 and 6.0 dB, respectively), but the differences were not statistically significant. Later measurements showed a statistically significant improvement in the mean ABG, 11.5 dB, compared with 4.4 dB for one of the standard partial ossicular replacement prosthesis and a tendency of better results to 6.9 dB of the other standard prosthesis. CONCLUSIONS: In our patients, we achieved similarly good audiometric results to those already published for the partial ossicular replacement prosthesis with a ball-and-socket joint between the plate and the shaft. Intraoperative fixation posed no problems, and the postoperative complication rate was low.

Treatment of cervical paragangliomas: is surgery the only way?

PURPOSE: To analyze the results after surgery or stereotactic radiotherapy (SRT) in the treatment of cervical paragangliomas. Against this background, the decision-making algorithm used in the treatment of carotid body tumors (CBTs) and vagal paragangliomas (VPs) was reevaluated relative to the existing literature on the topic. MATERIALS AND METHODS: Retrospective study between 2000 and 2012. A total of 27 CBTs and nine VPs in 32 patients were treated. Shamblin class I: 59.3% (n=16); class II: 29.6% (n=8); class III: 11.1% (n=3). Treatment modalities were surgery, radiotherapy, or observation. The end points for analysis were long-term tumor control and integrity of the cranial nerves. RESULTS: 21 CBTs and seven VPs underwent surgery; SRT was performed in three CBTs and two VPs. Three CBTs were clinically observed. Permanent nerve paresis followed after surgery for CBTs in five patients (20%) and in all patients with VPs. No impaired cranial nerve function resulted after SRT. The median follow-up period was 4.7 years. The tumor control rate after therapy for CBTs and VPs was 100%. One CBT that received clinical observation showed slow tumor progression. CONCLUSIONS: A surgical procedure should be regarded as the treatment of choice in patients with small CBTs. In larger CBTs, particularly in elderly patients with unimpaired cranial nerves, radical surgery should be regarded critically. As surgery for VPs caused regularly impairment of cranial nerves with functional disturbances of various degrees a comprehensive consultation with the patient is mandatory and nonsurgical strategies should be discussed.

First experience with the fiber-enabled CO2 laser in stapes surgery and a comparison with the "one-shot" technique.

OBJECTIVE: To compare bone conduction after fiber-enabled CO2 laser perforation of the stapes footplate with conduction after the "one-shot" technique during stapedotomy in patients with otosclerosis. STUDY DESIGN: Retrospective clinical study. SETTING: Tertiary reference center. MATERIALS AND METHODS: We evaluated data from 178 patients who had undergone primary stapedotomy for suspected stapedial ankylosis. The stapes footplate was perforated using a fiber-enabled CO2 laser in 89 patients and the "one-shot" technique in the other 89. Only consecutive surgery was considered. Bone conduction thresholds were determined at 0.5, 1, 2, and 4 kHz on the first and third postoperative days in all patients; 172 patients were followed up after 1 month. Audiograms were compared with preoperative bone conduction. RESULTS: The postoperative bone conduction threshold on Day 1 was significantly worse at almost all frequencies. At 0.5 and 2 kHz, it improved within a month and was significantly different from the preoperative value. Bone conduction threshold at 4 kHz showed the greatest deterioration immediately after surgery, improving considerably in 1 month but remaining worse than at baseline. Only at 1 kHz was there no significant immediate hearing loss. Direct comparison of the fiber-enabled CO2 laser and the "one-shot" technique showed no statistically significant differences. CONCLUSION: Compared with the "one-shot" technique, the fiber-enabled CO2 laser can be used safely in stapes surgery, without great risk to the patient. In our opinion, it has practical advantages, especially in difficult anatomic conditions.

Bone conduction after stapes surgery: comparison of CO2 laser and manual perforation.

OBJECTIVE: To compare bone conduction after 2 different ways of perforating the stapes footplate during stapedotomy in patients with otosclerosis. STUDY DESIGN: Retrospective clinical study. SETTING: Tertiary reference center. MATERIALS AND METHODS: This study evaluated data from 302 patients (61.2% women) who had undergone primary surgery for stapedial ankylosis between 2000 and 2010. Bone conduction thresholds at 0.5, 1, 2, and 4 kHz were determined on the first and fourth postoperative days in all patients; 280 patients were followed up after 1 month and 125 after 1 year. Audiograms were compared with preoperative bone conduction.A laser was used to open the stapes footplate in 180 patients; manual perforation was performed in 122. RESULTS: Immediately postoperatively the bone conduction threshold was significantly worse at almost all frequencies. At lower frequencies (0.5 and 1 kHz), it improved to baseline within the first 4 days. At 2 kHz, the threshold on Day 4 remained significantly worse than baseline and improved only after 1 month, then exceeding the preoperative value. Bone conduction at 4 kHz still tended to be worse than baseline 1 month after surgery, but the difference was no longer statistically significant 1 year later. A direct comparison with classic stapedotomy showed a trend in favor of the laser technique, but the difference was not statistically significant. CONCLUSION: Both laser and classic techniques can be used successfully in stapes surgery without causing long-term damage to the inner ear. Direct comparison shows a trend in favor of laser stapedotomy.

Head and neck paragangliomas: clinical and molecular genetic classification.

Head and neck paragangliomas are tumors arising from specialized neural crest cells. Prominent locations are the carotid body along with the vagal, jugular, and tympanic glomus. Head and neck paragangliomas are slowly growing tumors, with some carotid body tumors being reported to exist for many years as a painless lateral mass on the neck. Symptoms depend on the specific locations. In contrast to paraganglial tumors of the adrenals, abdomen and thorax, head and neck paragangliomas seldom release catecholamines and are hence rarely vasoactive. Petrous bone, jugular, and tympanic head and neck paragangliomas may cause hearing loss. The internationally accepted clinical classifications for carotid body tumors are based on the Shamblin Class I-III stages, which correspond to postoperative permanent side effects. For petrous-bone paragangliomas in the head and neck, the Fisch classification is used. Regarding the molecular genetics, head and neck paragangliomas have been associated with nine susceptibility genes: NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2 (SDH5), and TMEM127. Hereditary HNPs are mostly caused by mutations of the SDHD gene, but SDHB and SDHC mutations are not uncommon in such patients. Head and neck paragangliomas are rarely associated with mutations of VHL, RET, or NF1. The research on SDHA, SDHAF2 and TMEM127 is ongoing. Multiple head and neck paragangliomas are common in patients with SDHD mutations, while malignant head and neck paraganglioma is mostly seen in patients with SDHB mutations. The treatment of choice is surgical resection. Good postoperative results can be expected in carotid body tumors of Shamblin Class I and II, whereas operations on other carotid body tumors and other head and neck paragangliomas frequently result in deficits of the cranial nerves adjacent to the tumors. Slow growth and the tendency of hereditary head and neck paragangliomas to be multifocal may justify less aggressive treatment strategies.

Function-preserving therapy for jugulotympanic paragangliomas: a retrospective analysis from 2000 to 2010.

OBJECTIVES/HYPOTHESIS: Treatment for jugulotympanic paragangliomas (JTPs) is shifting from radical toward function-preserving surgery. Alternative primary treatments are available, such as stereotactic radiotherapy (SRT) and radiosurgery. The aim of this study was to analyze the results after primary function-preserving surgery with or without adjuvant radiotherapy, or primary SRT, in the treatment of JTPs. STUDY DESIGN: Retrospective analysis. METHODS: From 2000 to 2010, 45 patients (mean age, 62.5 years) received function-preserving treatment for JTPs-four type A paragangliomas (8.9%), 19 type B (42.2%), 13 type C (28.9%), and nine type D (20%) in the Fisch classification. The patients were retrospectively assigned to three groups: primary function-preserving surgery, primary stereotactic radiotherapy, and close follow-up. The end points for analysis were long-term tumor control, cranial nerve function, and hearing. RESULTS: A total of 64.4% of the patients (n = 29) received primary surgery, with complete resection in 18. Eleven patients had surgical tumor reduction, with fractionated postoperative radiotherapy (mean 53.5 Gy; range, 50-56 Gy) in five cases and radiosurgery (18 Gy) in one case; five patients received close follow-up. Twelve patients (26.7%) underwent primary radiotherapy (11 with SRT [mean, 50 Gy]; one with radiosurgery [16 Gy]). Four patients (8.9%) received a wait-and-scan strategy. The mean follow-up was 46.8 months. The overall tumor control rate was 97.2%. CONCLUSIONS: With these high tumor control rates, consistent with the literature, function-preserving therapy for JTPs currently appears to offer the greatest benefit for patients.

Head and neck paragangliomas: clinical and molecular genetic classification

Head and neck paragangliomas are tumors arising from specialized neural crest cells. Prominent locations are the carotid body along with the vagal, jugular, and tympanic glomus. Head and neck paragangliomas are slowly growing tumors, with some carotid body tumors being reported to exist for many years as a painless lateral mass on the neck. Symptoms depend on the specific locations. In contrast to paraganglial tumors of the adrenals, abdomen and thorax, head and neck paragangliomas seldom release catecholamines and are hence rarely vasoactive. Petrous bone, jugular, and tympanic head and neck paragangliomas may cause hearing loss. The internationally accepted clinical classifications for carotid body tumors are based on the Shamblin Class I-III stages, which correspond to postoperative permanent side effects. For petrous-bone paragangliomas in the head and neck, the Fisch classification is used. Regarding the molecular genetics, head and neck paragangliomas have been associated with nine susceptibility genes: NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2 (SDH5), and TMEM127. Hereditary HNPs are mostly caused by mutations of the SDHD gene, but SDHB and SDHC mutations are not uncommon in such patients. Head and neck paragangliomas are rarely associated with mutations of VHL, RET, or NF1. The research on SDHA, SDHAF2 and TMEM127 is ongoing. Multiple head and neck paragangliomas are common in patients with SDHD mutations, while malignant head and neck paraganglioma is mostly seen in patients with SDHB mutations. The treatment of choice is surgical resection. Good postoperative results can be expected in carotid body tumors of Shamblin Class I and II, whereas operations on other carotid body tumors and other head and neck paragangliomas frequently result in deficits of the cranial nerves adjacent to the tumors. Slow growth and the tendency of hereditary head and neck paragangliomas to be multifocal may justify less aggressive treatment strategies.

Results obtained with a new superelastic nitinol stapes prosthesis in stapes surgery.

OBJECTIVE: The trimmable nitinol-polytetrafluoroethylene stapes prosthesis is a novel prosthesis that features a band-shaped nitinol loop. Unlike the SMart prosthesis, which uses the heat-activated self-crimping property of the alloy for fixation to the long process of the incus, this new prosthesis uses the property of superelasticity. The objective of the present study was to assess the hearing outcomes and intraoperative handling of the first 31 prostheses to be implanted in a primary stapes operation and to compare the results and experience thus obtained with those previously achieved with SMart prostheses. STUDY DESIGN: Retrospective clinical study. SETTING: Tertiary reference center. PATIENTS: The results obtained in the first 31 patients (16 women and 15 men) in whom a nitinol prosthesis was implanted in a primary stapes operation between May 2009 and April 2010 were assessed and compared with those obtained in the first 31 patients (23 women and 8 men) to receive a SMart prosthesis between October 2004 and September 2005. INTERVENTION: Primary stapes surgery. MAIN OUTCOME MEASURES: Audiometry was performed preoperatively, and after a mean follow-up period of 26.9 days (standard deviation [SD], ± 16 d) in the nitinol group and 26.2 days (SD, ± 22 d) in the SMart group. Audiometry was repeated in 18 patients in the nitinol group and in 21 patients in the SMart group after a mean period of 480 days (SD, ± 118 d) and 495 days (SD, ± 160 d), respectively. RESULTS: All the nitinol-polytetrafluoroethylene prostheses were implanted without problem. Fixation was simpler than with the SMart piston prosthesis. In the nitinol group, mean ABG3000 and ABG4000 were 9.5 dB (SD, ± 5.7 dB) and 10.7 dB (SD, ± 6.1 dB), respectively, with an improvement of 21.8 dB (SD, ± 8.0 dB) and 21.7 dB (SD, ± 7.9 dB), respectively. The corresponding values in the SMart piston group were 8.9 dB (± 4.3 dB) and 10.0 dB (± 5.2 dB), respectively, with an improvement of 21.2 ± 8.2 dB and 20.8 ± 8.3 dB, respectively. At the second follow-up, the values in the nitinol group were 4.4 dB (SD, ± 3.1 dB) for ABG3000 and 6.5 dB (SD, ± 4.3 dB) for ABG4000, with a mean improvement of 27.9 ± 6.0 dB and 27.0 ± 6.9 dB, respectively, whereas in the SMart group, the values were 5.7 ± 5.0 dB for ABG3000 and 6.4 ± 4.0 dB for ABG4000, with a mean improvement of 24.9 ± 7.2 and 24.7 ± 7.9 dB, respectively. These results did not differ to a statistically significant extent between the 2 groups. CONCLUSION: The hearing outcomes obtained with the new superelastic nitinol prosthesis were similar to those that we had obtained previously with the SMart prosthesis. The fixation mechanism is simpler than with other types of prosthesis; however, the loop of the prosthesis seems not to be equally suitable for all diameters of the long process of the incus.

Involvement of the anterior semicircular canal in posttraumatic benign paroxysmal positioning vertigo.

OBJECTIVE: To study the involvement of the different semicircular canals in posttraumatic benign paroxysmal positioning vertigo (BPPV) with special reference to the anterior canal (AC). STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: Seventy-four BPPV patients. INTERVENTIONS: Neurotologic assessment with video-oculography; treatment of BPPV with the canalith repositioning procedure appropriate for the affected semicircular canal. MAIN OUTCOME MEASURES: Number of patients with AC, posterior canal (PC), horizontal canal (HC), and multiple-canal involvement in posttraumatic versus idiopathic BPPV. RESULTS: 85.1% of patients were classified as idiopathic BPPV, whereas 14.9% had a history of posttraumatic BPPV. The prevalence of AC BPPV was significantly higher in the posttraumatic group (27.3%) compared with that in the idiopathic group (3.2%; Fisher's exact test: p = 0.021). Multiple-canal (combined) BPPV was observed more frequently after head trauma (27.3%) compared with the idiopathic form of the disorder (1.6%; p = 0.009). In particular, the risk for combined AC/PC BPPV was greater in posttraumatic than idiopathic cases (odds ratio, 13.78; 95% confidence interval, 1.13-167.8). No significant differences were observed for the involvement of the PC and HC between the two groups. Two cases of combined AC/PC BPPV are presented with particular respect to the underlying trauma mechanism. CONCLUSION: Head trauma is a risk factor for AC and combined BPPV, in particular AC/PC BPPV. Involvement of the AC should especially be considered in patients who experienced head trauma resulting in a nonupright position of the body.

Retrospective analysis of the results of implanting Nitinol pistons with heat-crimping piston loops in stapes surgery.

The study presented here evaluates the hearing results after the implantation of a new nickel-titanium (Nitinol) prosthesis in stapes surgery; on heating, this prosthesis crimps itself around the long process of the incus. In addition, we compare the outcome with results published in the literature. The medical records of all patients who underwent surgery for otosclerosis with implantation of a Nitinol piston during the period 2004-2006 were evaluated retrospectively. 83 patients (58 women and 25 men), with a provisional diagnosis of otosclerosis that was confirmed during surgery in all but one of the cases, were treated by primary stapes surgery (85 ears). We were able to include 53 patients (55 ears) who had audiograms with air and bone conduction preoperatively and both 2-6 weeks and about 1 year after surgery. We found a mean air-bone gap (ABG) for the frequencies 0.5, 1, 2 and 4 kHz (ABG4000) of 10.4 ± 5.5 dB after a mean postoperative follow-up period of 24.5 ± 16 days, and of 7.4 ± 3.7 dB after 462 ± 119 days. For the frequencies 0.5, 1, 2 and 3 kHz (ABG3000), the results were 9.1 ± 4.8 and 6.4 ± 3.9 dB. The differences in preoperative versus postoperative air-bone gap, referred to as ABGC, after 25 and 462 days, respectively, were 19.4 ± 8.9 and 22.3 ± 8.8 dB for AGB4000, and 19.5 ± 8.8 and 22.2 ± 8.9 for ABG3000. Very good results were achieved with a new nickel-titanium prosthesis that crimps itself around the long process of the incus, thus facilitating stapes surgery and at the same time stabilizing the high quality of the results. However, no long-term results after 10 years or more, which would allow a final judgment, are yet available.

First experience with a new titanium clip stapes prosthesis and a comparison with the earlier model used in stapes surgery.

OBJECTIVES/HYPOTHESIS: The aim of the study was to gain the first clinical experience with a new titanium clip prosthesis in stapes surgery, and to compare this model with its predecessor. We placed particular emphasis on the practicability of fixing the prosthesis to the long process of the incus and on the postoperative improvement in hearing. STUDY DESIGN: Retrospective chart review. METHODS: The study included 23 patients who had a CliP Piston àWengen fitted and 21 patients with a Soft CliP Piston (both from Kurz Medizintechnik, Dusslingen, Germany). Air and bone conduction were tested preoperatively and 5 to 6 weeks after surgery in all patients, as well as after about 1 year in a subgroup. RESULTS: We found a mean air-bone gap of 8.5 +/- 5.2 dB in the frequencies 0.5, 1, 2, and 3 kHz for the patients with a CliP Piston àWengen at follow-up audiometry after an average of 31 days, and of 6.4 +/- 3.7 dB for 11 patients after 412 days. The corresponding figures for patients with Soft CliP Pistons were 8.9 +/- 4.1 dB after 44 days, and 6.3 +/- 5.6 dB for 10 patients after 419 days. There were no statistically significant differences. All the prostheses were implanted without difficulty. CONCLUSIONS: The two stapes prostheses studied gave good early audiometric results that showed no difference. After a short learning period, both could be pushed onto the long process of the incus with similar ease, although subjectively the new design of the Soft CliP seemed to adapt better to the different diameters of the process and took up less space in the middle ear.

Clinical predictors for germline mutations in head and neck paraganglioma patients: cost reduction strategy in genetic diagnostic process as fall-out.

Multiple genes and their variants that lend susceptibility to many diseases will play a major role in clinical routine. Genetics-based cost reduction strategies in diagnostic processes are important in the setting of multiple susceptibility genes for a single disease. Head and neck paraganglioma (HNP) is caused by germline mutations of at least three succinate dehydrogenase subunit genes (SDHx). Mutation analysis for all 3 costs approximately US$2,700 per patient. Genetic classification is essential for downstream management of the patient and preemptive management of family members. Utilizing HNP as a model, we wanted to determine predictors to prioritize the most heritable clinical presentations and which gene to begin testing in HNP presentations, to reduce costs of genetic screening. Patients were tested for SDHB, SDHC, and SDHD intragenic mutations and large deletions. Clinical parameters were analyzed as potential predictors for finding germline mutations. Cost reduction was calculated between prioritized gene testing compared with that for all genes. Of 598 patients, 30.6% had SDHx germline mutations: 34.4% in SDHB, 14.2% SDHC, and 51.4% SDHD. Predictors for an SDHx mutation are family history [odds ratio (OR), 37.9], previous pheochromocytoma (OR, 10.9), multiple HNP (OR, 10.6), age

Presynaptic protein distribution and odour mapping in glomeruli of the olfactory bulb of Xenopus laevis tadpoles.

The sensory input layer in the olfactory bulb (OB) is typically organized into spheroidal aggregates of dense neuropil called glomeruli. This characteristic compartmentalization of the synaptic neuropil is a typical feature of primary olfactory centres in vertebrates and most advanced invertebrates. In the present work we mapped the location of presynaptic sites in glomeruli across the OB using antibodies to presynaptic vesicle proteins and presynaptic membrane proteins in combination with confocal microscopy. In addition the responses of glomeruli upon mucosal application of amino acid-odorants and forskolin were monitored using functional calcium imaging. We first describe the spatial distribution of glomeruli across the main olfactory bulb (MOB) in premetamorphic Xenopus laevis. Second, we show that the heterogeneous organization of glomeruli along the dorsoventral and mediolateral axes of the MOB is associated with a differential distribution of synaptic vesicle proteins. While antibodies to synaptophysin, syntaxin and SNAP-25 uniformly labelled glomeruli in the whole MOB, intense synaptotagmin staining was present only in glomeruli in the lateral, and to a lesser extent in the intermediate, part of the OB. Interestingly, amino acid-responsive glomeruli were always located in the lateral part of the OB, and glomeruli activated by mucosal forskolin application were exclusively located in the medial part of the OB. This correlation between odour mapping and presynaptic protein distribution is an additional hint on the existence of different subsystems within the main olfactory system in larval Xenopus laevis.

Response profiles to amino acid odorants of olfactory glomeruli in larval Xenopus laevis.

Glomeruli in the vertebrate olfactory bulb (OB) appear as anatomically discrete modules receiving direct input from the olfactory epithelium (OE) via axons of olfactory receptor neurons (ORNs). The response profiles with respect to amino acids (AAs) of a large number of ORNs in larval Xenopus laevis have been recently determined and analysed. Here we report on Ca(2+) imaging experiments in a nose-brain preparation of the same species at the same developmental stages. We recorded responses to AAs of glomeruli in the OB and determined the response profiles to AAs of individual glomeruli. We describe the general features of AA-responsive glomeruli and compare their response profiles to AAs with those of ORNs obtained in our previous study. A large number of past studies have focused either on odorant responses in the OE or on odorant-induced responses in the OB. However, a thorough comparison of odorant-induced responses of both stages, ORNs and glomeruli of the same species is as yet lacking. The glomerular response profiles reported herein markedly differ from the previously obtained response profiles of ORNs in that glomeruli clearly have narrower selectivity profiles than ORNs. We discuss possible explanations for the different selectivity profiles of glomeruli and ORNs in the context of the development of the olfactory map.