Faculty Bibliography

A prominent feature of cortical pyramidal neurons is the presence of an apical dendrite, and the spatial organization of synaptic contacts within the dendritic arbor is critical for neuronal integration and function (Stuart et al., 1999). Here we report that the time scales for synaptic plasticity and temporal interactions are shorter for proximal inputs than for distal inputs onto the apical dendrite of layer 2/3 pyramidal neurons. Whole-cell recordings were made from the soma and apical dendrite of layer 2/3 pyramidal cells in slices of rat visual cortex. Independent EPSPs were evoked by focal extracellular stimulation near the apical dendrite (<15 mum) either proximally (<50 mum) or distally (>100 mum). Spike-timing-dependent long-term depression (LTD) was induced by repetitively pairing a postsynaptic spike with a subsequent EPSP. The timing requirements for LTD were prolonged for distal inputs (<100 ms post-before-pre) relative to proximal inputs (<50 ms). We next examined if post-before-pre pairing produced some immediate effect that might be responsible for LTD induction. When evoked after a backpropagating action potential, the amplitude of distal EPSPs was suppressed up to 75 ms afterward, while proximal inputs were suppressed only up to 30 ms. BAPTA prevented the late phase of distal suppression, showing that EPSPs are regulated by a calcium-dependent process initiated by the backpropagating spike. Including 4-AP in the recording electrode widened both the time window for proximal EPSP suppression and the window for induction of spike-timing LTD, suggesting that suppression of the EPSP may contribute to LTD induction. These results demonstrate that proximal and distal regions of the apical dendrite are differentially sensitive to the temporal pattern of input. This spatial axis for temporal interactions may have important functional consequences for synaptic development and integration

Neurons of the inferior olivary nucleus (IO) form the climbing fibers that excite Purkinje cells of the cerebellar cortex. IO neurons are electrically coupled through gap junctions, and they generate synchronous, subthreshold oscillations of membrane potential at approximately 5-10 Hz. Experimental and theoretical studies have suggested that both the rhythmicity and synchrony of IO neurons require electrical coupling. We recorded from pairs of IO neurons in slices of mouse brainstem in vitro. Most pairs of neurons from wild-type (WT) mice were electrically coupled, but coupling was rare and weak between neurons of knock-out (KO) mice for connexin36, a neuronal gap junction protein. IO cells in both WT and KO mice generated rhythmic membrane fluctuations of similar frequency and amplitude. Oscillations in neighboring pairs of WT neurons were strongly synchronized, whereas the oscillations of KO pairs were uncorrelated. Spontaneous oscillations in KO neurons were not blocked by tetrodotoxin. Spontaneously oscillating neurons of both WT and KO mice generated occasional action potentials in phase with their membrane rhythms, but only the action potentials of WT neuron pairs were synchronous. Harmaline, a beta-carboline derivative thought to induce tremor by facilitating rhythmogenesis in the IO, was injected systemically into WT and KO mice. Harmaline-induced tremors were robust and indistinguishable in the two genotypes, suggesting that gap junction-mediated synchrony does not play a role in harmaline-induced tremor. We conclude that electrical coupling is not necessary for the generation of spontaneous subthreshold oscillations in single IO neurons, but that coupling can serve to synchronize rhythmic activity among IO neurons.

Neurons possess multiple voltage-dependent conductances specific for their function. To investigate how low-threshold outward currents improve the detection of small signals in a noisy background, we recorded from gerbil medial superior olivary (MSO) neurons in vitro. MSO neurons responded phasically, with a single spike to a step current injection. When bathed in dendrotoxin (DTX), most cells switched to tonic firing, suggesting that low-threshold potassium currents (I(KLT)) participated in shaping these phasic responses. Neurons were stimulated with a computer-generated steady barrage of random inputs, mimicking weak synaptic conductance transients (the 'noise'), together with a larger but still subthreshold postsynaptic conductance, EPSG (the 'signal'). DTX reduced the signal-to-noise ratio (SNR), defined as the ratio of probability to fire in response to the EPSG and the probability to fire spontaneously in response to noise. The reduction was mainly attributable to the increase of spontaneous firing in DTX. The spike-triggered reverse correlation indicated that, for spike generation, the neuron with I(KLT) required faster inward current transients. This narrow temporal integration window contributed to superior phase locking of firing to periodic stimuli before application of DTX. A computer model including Hodgkin-Huxley type conductances for spike generation and for I(KLT) (Rathouz and Trussell, 1998) showed similar response statistics. The dynamic low-threshold outward current increased SNR and the temporal precision of integration of weak subthreshold signals in auditory neurons by suppressing false positives

Objective: Based on a few reports that describe obstructive sleep apnea (OSA) patients as having an increased risk of acute upper airway obstruction (UAO) after pharmacological sedation, this population is less likely to receive sedation prior to surgery. Our objective was to evaluate pediatric patients with sleep-disordered breathing who received preoperative sedation to determine if there was an increase in preoperative airway obstruction. Design: Retrospective chart review from 1995 to 2000. Setting: Two tertiary care academic medical centers. Patients: Sixty-five children (mean age= 4.7 +/- 2.3 years; 49 boys, 16 girls) diagnosed with sleep-disordered breathing by sleep study or clinical evaluation that received preoperative midazolam hydrochloride. Outcome measure: The occurrence of preoperative adverse events defined as UAO, hypoventilation, desaturation, bradycardia, or sustained lethargy that required active intervention after the administration of midazolam hydrochloride within 24 It of surgery. Results: None of the 65 children evaluated in this study experienced respiratory compromise requiring intervention after the administration of preoperative sedation. Potential risk factors such as patients' age, sex, weight, comorbidities, midazolam hydrochloride dose, and severity of sleep apnea did, not appear to affect outcome. Conclusion: The preliminary data suggested that preoperative sedation might be safely administered to children with mild or moderate sleep-disordered breathing, and possibly to children with severe OSA, if children are closely observed prior to surgery. Further prospective studies are needed to confirm these results. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved

OBJECTIVES: The differential diagnosis and treatment of patients with chronic cough, paradoxical vocal fold motion, and disordered breathing can be a challenge to most practicing otolaryngologists. Tracheobronchial (ie, asthma, bronchitis, and tracheal stenosis), laryngeal (ie, vocal fold paralysis and neoplasms), and rhinologic (ie, allergies and rhinosinusitis) etiologies are commonly diagnosed and treated effectively. However, occasionally one is faced with patients who are refractory to medical treatment and have no obvious rhinologic, laryngeal or pulmonary cause. STUDY DESIGN AND SETTING: We conducted a review of the literature. METHODS: We present a thorough review of the current medical literature exploring the complex neurologic mechanisms involved in the production of cough and the relationship between gastroesophageal reflux disease, vagal neurapathy, and paradoxical vocal fold motion. RESULTS: The diagnosis and successful treatment of chronic cough can be complex. It requires a thorough understanding of the neurologic mechanisms behind cough excitation and suppression. Successful treatment strategies include aggressive management of the patient's reactive airway disease, gastroesophageal reflux disease, and, in select cases, paradoxical vocal fold motion. This may involve a well-coordinated effort among pulmonologists, otolaryngologists, gastroenterologists, and speech pathologists. CONCLUSION: Gastroesophageal reflux disease, vagal neuropathy, and paradoxical vocal fold motion are additional causes of chronic cough and disordered breathing that need to be considered, in the absence of obvious laryngotracheal and/or rhinologic pathology. A high index of suspicion is essential in making the diagnosis and formulating an effective multidisciplinary treatment plan for these patients

OBJECTIVES/HYPOTHESIS: Hurthle cell tumors are a variant of follicular cell neoplasms. The purpose of the study was to determine the reliability of intraoperative frozen-section analysis for diagnosing Hurthle cell carcinoma and Hurthle cell neoplasm and to evaluate age, gender, and tumor size differences in the incidence of Hurthle cell carcinoma. STUDY DESIGN: Retrospective chart review. METHODS: The records of all patients undergoing thyroid surgery at Long Island Jewish Medical Center (Long Island Campus of the Albert Einstein College of Medicine, New Hyde Park, NY) from 1990 to 2000 were reviewed. Patients were identified whose final pathological finding was Hurthle cell neoplasm or Hurthle cell carcinoma. Age at diagnosis, gender, tumor size, and correlation between frozen-section analysis and final pathological finding was determined. RESULTS: One hundred sixteen patients had Hurthle cell tumors on final pathological finding (49 had Hurthle cell carcinoma and 67 had Hurthle cell neoplasm). Eleven of these patients had incidental papillary carcinoma. There were 24 men and 92 women. Sixty-seven percent of the men (16 of 24) and 36% of the women (33 of 92) had Hurthle cell carcinoma on final pathological finding. The mean ages for Hurthle cell neoplasm and Hurthle cell carcinoma groups were 53 (median age, 50 y) and 58 years (median age, 61 y), respectively. One hundred eleven patients had intraoperative frozen-section analysis. Of the 49 patients with Hurthle cell carcinoma, 9 (19%) were diagnosed by frozen-section analysis, 36 (75%) had indeterminate frozen-section analysis, 3 (6%) were discovered to have papillary carcinoma on frozen-section analysis, and 1 did not have a frozen-section analysis. Multivariate analysis indicated that size correlated with malignancy and that gender did not (P =.0015). CONCLUSIONS: In the study population, only 19% of patients were discovered to have Hurthle cell carcinoma on frozen-section analysis. Sixty-seven percent of men with Hurthle cell neoplasm had malignancies, compared with 36% of women, and this difference was statistically significant