Lateral intraparietal area (LIP) neurons are thought to compute the decision of where to look. Specifically, their firing rate is thought to represent accumulated evidence for a decision by ramping up to a high level, the putative decision bound, before an eye movement to a given location. However, LIP neurons are also highly responsive to visual stimuli. Because all previous research put a visual stimulus (a saccadic target) in the response field (RF) location of a neuron during decision formation, it is unknown if LIP neurons can still show decision computation without this visual drive. We therefore recorded the spiking activity of LIP neurons in a conventional decision task where a monkey decides the direction of a noisy motion stimulus and indicates his decision with a saccade. On half the trials, the Choice Targets remained on for the whole trial, as is conventionally done. On the remaining trials, targets were flashed at the beginning of the trial and absent during motion-viewing. Furthermore, we recorded the activity of any neuron with an RF, instead of only neurons exhibiting persistent memory activity before an instructed saccade. This enabled us to also test the long-held assumption that only cells with persistent memory activity show decision signals. Our results show that 1) cells without persistent activity indeed show decision signals, 2) population response drops without RF stimulation (although individual neurons were affected in diverse ways), 3) distinct, repeating response “motifs” exist among cells, 4) a signal exists where neural response is lower for stronger motion strength stimuli, regardless of direction. These results prove that contrary to dogma, a neuron’s ability to show a long “memory” response is not related to an ability to accumulate evidence over time for a decision. Also, LIP firing rate cannot be interpreted as a pure decision variable because it simultaneously represents decision-irrelevant, visual stimuli. Finally, diverse, but repeating responses among cells suggest the existence of cell types in LIP. These results demonstrate that LIP acts as a bank of potentially useful signals, and raises the question of how they might be used for a decision. / text

published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

Auditory receptor cells rely on force-gated channels to transform sound stimuli into neural activity. These primary auditory neurons form the first stage of the neural circuits that support a host of higher-order functions, such as the localization of sound or the comprehension of speech. The mechanisms of sound transduction, as well as higher-order processes such as acoustic communication during courtship, can be studied in the fruit fly Drosophila melangogaster, a model organism with a suite of powerful genetic tools. However, this work is hampered by incomplete knowledge of the components of the Drosophila auditory system and a lack of high resolution techniques for investigating their function. We used several approaches to identify candidate Drosophila central auditory neurons and developed techniques for measuring the activity of identified neurons in vivo. As an outgrowth of this work, we also developed a non-invasive method for measuring generator currents in the primary auditory neurons. Chapter 4 describes this technique and provides a basic characterization of the sensitivity of the Drosophila auditory system to sound. Determining the sensitivity of the Drosophila auditory system is necessary for understanding the neural basis of acoustic communication and has implications for the mechanism of transduction. The force-gated ion channel that transforms sound into an electrical signal has not been identified in any species. Several TRP channels have been implicated in Drosophila auditory transduction, but mechanistic studies have been hampered by the inability to record subthreshold signals from auditory receptor neurons. We recorded generator currents from primary auditory neurons to assess the roles of several TRP family members in transduction. We found that the TRPN family member NompC is not required for transduction, despite the fact that it is required for the active amplification of motion by the auditory organ. Instead, NompC is required for a process that sensitizes the transduction complex to movement and regulates the resting forces on the complex. In contrast, the TRPV channels Nanchung and Inactive are required for responses to sound, suggesting they are components of the transduction complex. Thus, transduction and active amplification are genetically separable processes in the Drosophila auditory system.

published_or_final_version / Physics / Master / Master of Philosophy

No description available.

Εισαγωγή: Οι υπερκοιλιακές ταχυκαρδίες (ΥΤ) αποτελούν σημαντική αιτία νοσηρότητας στα παιδιά. Λόγω της χρονιότητας των συμπτωμάτων, η αντιαρρυθμική φαρμακευτική αγωγή δεν είναι ιδεώδης λύση. Η κατάλυση με ρεύμα ραδιοσυχνότητας (ΡΡ) μπορεί να προσφέρει ριζική θεραπεία. Στόχος: Η μελέτη αυτή είχε ως στόχο την ανάλυση των αποτελεσμάτων κατάλυσης υπερκοιλιακής ταχυκαρδίας (ΥΤ) στα παιδιά με ρεύμα ραδιοσυχνότητας (ΡΡ). Μεθοδολογία: Εξετάσαμε αναδρομικά τα στοιχεία 140 παιδιών ηλικίας 4-18 (12,8±3,5) ετών με ΥΤ που υπεβλήθησαν σε πλήρη ηλεκτροφυσιολογικό έλεγχο και κατάλυση με ΡΡ, είτε υπό γενική αναισθησία (84), είτε υπό καταστολή (56). Αποτελέσματα: Η τελική επιτυχία της κατάλυσης με ΡΡ μετά από τυχόν υποτροπές, ήταν 90/94 (95,7%) για ασθενείς (Α) με παραπληρωματικά δεμάτια (ΠΔ), 36/37 (97,3%) για Α με κομβική ταχυκαρδία επανεισόδου (ΚΤΕ), 10/10 για Α με έκτοπη κολπική ταχυκαρδία (ΕΚΤ), 3/3 για Α με κολπική ταχυκαρδία επανεισόδου και 1/1 για Α έκτοπη κομβική ταχυκαρδία. Σε Α με πρόσθια/διάμεσα διαφραγματικά ΠΔ παρατηρήθηκε υψηλότερος χρόνος ακτινοσκόπησης (p=0,05) και χαμηλότερη τελική επιτυχία (p=0,02). Οι υπόλοιπες κατηγορίες είχαν παρόμοια μεταξύ τους αποτελέσματα. Τα δεξιά πλάγια ΠΔ είχαν υψηλότερο ποσοστό συγγενών καρδιοπαθειών (p<0,001). Οι υποτροπές ήταν συχνότερες σε Α με πολλαπλά ΠΔ (p=0,007). Το ποσοστό μόνιμων σοβαρών επιπλοκών ήταν 1,4% (1 Α με ανεπάρκεια αορτής μετά από κατάλυση αριστερού ΠΔ με διαορτική τεχνική και 1 Α με πλήρη κολποκοιλιακό αποκλεισμό μετά από κατάλυση ΚΤΕ). Η τελική επιτυχία της επέμβασης, και τα ποσοστά υποτροπών και επιπλοκών ήταν ανεξάρτητα της ηλικίας. Συμπεράσματα: Η κατάλυση με ΡΡ μπορεί να αποτελέσει ριζική θεραπεία των ΥΤ στα παιδιά, χωρίς διαφορές στα αποτελέσματα σε ηλικίες >4 ετών. / Background: Supraventricular tachycardia (SVT) represents a significant cause of morbidity in children. Because of the chronic course, long-term treatment with antiarrythmic drugs is not an ideal solution. Radiofrequency ablation (RFA) may offer curative treatment. Purpose: The purpose of this study was to analyze the outcome of radiofrequency ablation (RFA) of supraventricular tachycardia (SVT) in children. Methodology: We reviewed retrospectively the charts of 140 patients (pts) 4-18 (12,8±3,5) years of age, who underwent complete electrophysiologic study and RFA., either under general anesthesia (84), or conscious sedation (56). Results: The final success of RFA, after possible recurrences, was 90/94 (95,7%) for pts with accessory pathways (AP), 36/37 (97,3%) for pts with AV nodal reentry tachycardia (AVNRT), 10/10 for pts with ectopic atrial tachycardia, 3/3 for pts with atrial reentry tachycardia, and 1/1 for a pt with junctional ectopic tachycardia. Longer fluoroscopy time (p=0,05) and lower final success (p=0,02) was observed in pts with anterior/mid-septal AP. The remaining categories had comparable results. Patients with right lateral AP had a higher prevalence of congenital heart disease (p<0,001). Recurrences were more frequent in pts with multiple AP (p=0,007). The incidence of severe permanent complications was 1,4% (1 pt with aortic insufficiency after retrograde RFA of left lateral AP, and 1 pt with complete AV block after RFA of AVNRT). The final success, recurrence rates and complication rates were independent of age. Conclusions: Treatment of SVT in children with RFA may offer permanent cure, without differences in outcomes in pts older than 4 years of age.

Phosphodiesterases (PDEs) are the enzymes responsible for the hydrolysis of cyclic nucleotides including cAMP and cGMP. We recently discovered that natriuretic peptides elicit effects in the atrial myocardium via a PDE dependant pathway; however, the role(s) of specific PDE subtypes in atrial myocytes are not clear. Thus, I studied the effects of PDE selective blockers on mouse atrial action potentials (APs) and L-type Ca2+ currents (ICa,L). AP duration (APD) was significantly increased in the presence of IBMX (inhibits all PDEs) as well as EHNA (PDE2 inhibitor) and rolipram (PDE4 inhibitor). The PDE 3 inhibitor milrinone had no effect on APD. Applying milrinone and rolipram (PDE3/PDE4 inhibition) or EHNA, milrinone, and rolipram (PDE2/ PDE3/PDE4 inhibition) in combination prolonged APD as effectively as IBMX. A similar pattern of results was obtained for atrial ICa,L. These data provide novel insight into the unique effects of PDE inhibitors in atrial myocytes

Glucose is the primary metabolic signal reflecting the current energy state of the body. Glucose influences the excitability of neurons in the area postrema (AP), a circumventricular organ (CVO), prompting my interest in investigating whether the subfornical organ (SFO), another sensory CVO can also detect glucose. Using patch-clamp electrophysiology, we investigated the influence of changing glucose concentrations on the excitability of SFO neurons. In dissociated SFO neurons, altering the bath concentration of glucose (1mM, 5mM, 10mM) influenced the excitability of 49% of neurons tested (n=67). Glucose-inhibited (GI, hyperpolarized by increased glucose or depolarized by decreased glucose) and glucose-excited (GE, depolarized by increased glucose or hyperpolarized by decreased glucose) neurons were observed. GI neurons (27%, n=18) depolarized in response to decreased glucose (n=10, mean 4.6 ± 1.0 mV) or hyperpolarized in response to increased glucose (n=8, mean -4.4 ± 0.8 mV). In contrast, GE neurons (22%, n=15) depolarized in response to increased glucose (n=9, mean 6.4 ± 0.4) or hyperpolarized in response to decreased glucose (n=6, mean -4.8 ± 0.6 mV). These data show that glucose acts on a subpopulation of SFO neurons to produce both excitatory and inhibitory actions. Using voltage-clamp recordings two groups of SFO neurons were identified: those producing an outward current (GI) and those producing an inward current (GE) in response to increasing concentrations of glucose from 1 to 10 mM (n=23). The mean glucose-induced inward current had a reversal potential of -24 ± 12 mV (mean input resistance 2.0 ± 0.4 GΩ, n= 5), suggesting it may be mediated by a NSCC. The mean glucose-induced outward current (mean input resistance 1.7 ± 0.3 GΩ, n=7) had a mean reversal potential of -78 mV ± 1.2 mV (n = 5), suggesting it may be mediated by an activation of either K+ or Cl-current (ECl = -67 mV, EK = -89 mV). The SFO has projections to the PVN, a regulator of energy balance. I investigated the effects of increasing concentrations of glucose (1 to 10 mM) on the membrane potential of dissociated SFO neurons projecting to the PVN. Thirty percent of SFO-PVN neurons tested (n=10) responded with membrane hyperpolarizations (mean -4.2 ± 0.8 mV, n=3) suggesting a proportion of these cells are GI neurons. These data indicate that SFO neurons are glucose-responsive, which supports a role for the SFO as a regulator of energy balance. / Thesis (Master, Physiology) -- Queen's University, 2009-09-24 20:20:33.319

No description available.

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