Biomedical subjects

George A Spirou

Publications and source records attributed to George A Spirou.

5 recordsLinked to original sources

PubMed2006

Synaptogenesis of the calyx of Held: rapid onset of function and one-to-one morphological innervation.

Synaptogenesis during early development is thought to follow a canonical program whereby synapses increase rapidly in number and individual axons multiply-innervate nearby targets. Typically, a subset of inputs then out-competes all others through experience-driven processes to establish stable, long-lasting contacts. We investigated the formation of the calyx of Held, probably the largest nerve terminal in the mammalian CNS. Many basic functional and morphological features of calyx growth have not been studied previously, including whether mono-innervation, a hallmark of this system in adult animals, is established early in development. Evoked postsynaptic currents, recorded from neonatal mice between postnatal day 1 (P1) and P4, increased dramatically from -0.14 +/- 0.04 nA at P1 to -6.71 +/- 0.65 nA at P4 with sharp jumps between P2 and P4. These are the first functional assays of these nascent synapses for ages less than P3. AMPA and NMDA receptor-mediated currents were prominent across this age range. Electron microscopy (EM) revealed a concomitant increase, beginning at P2, in the prevalence of postsynaptic densities (16-fold) and adhering contacts (73-fold) by P4. Therefore, both functional and structural data showed that young calyces could form within 2 d, well before the onset of hearing around P8. Convergence of developing calyces onto postsynaptic targets, indicative of competitive processes that precede mono-innervation, was rare (4 of 29) at P4 as assessed using minimal stimulation electrophysiology protocols. Serial EM sectioning through 19 P4 cells further established the paucity (2 of 19) of convergence. These data indicate that calyces of Held follow a noncanonical program to establish targeted innervation that occurs over a rapid time course and precedes auditory experience.

Aging↗

PubMed2003

Three-dimensional reconstruction of immunolabeled neuromuscular junctions in the human thyroarytenoid muscle.

OBJECTIVES/HYPOTHESIS: The objective was to reveal the location of the neuromuscular junctions in a three-dimensional reconstruction of the human thyroarytenoid muscle within the true vocal fold. STUDY DESIGN: Immunohistochemical analysis of serially sectioned human true vocal folds was performed, followed by reconstruction in three dimensions using computer imaging software. METHODS: Six fresh human larynges from autopsy were harvested, fixed in formalin, and embedded in paraffin. Eight vocal cords were studied from these six larynges. Five-micron serial sections were collected throughout the entire vocal cord in an axial plane at 500-microm intervals. Immunohistochemical analysis was performed with anti-synaptophysin antibody. A computer-controlled imaging and reconstruction system was used to create a three-dimensional reconstruction from the serial sections and to represent the location of the clustered band of neuromuscular junctions within each true vocal fold. The vocal cord was divided into equal thirds from anterior to posterior for statistical analysis. RESULTS: The most neuromuscular junctions (74%) were located in the middle third, and the least (7%) were found in the anterior third. The difference in anterior-to-posterior distribution was statistically significant in all eight specimens by chi2 analysis (P <.001). CONCLUSION: The distribution of neuromuscular junctions is not random within the human thyroarytenoid muscle. Because neuromuscular junctions are most highly concentrated in a band within the mid belly of the muscle, botulinum toxin type A (Botox) injection in patients with spasmodic dysphonia should be targeted to this region.

Adult↗

PubMed2002

Physiological response properties of neurons in the superior paraolivary nucleus of the rat.

The superior paraolivary nucleus (SPON) is a prominent nucleus of the superior olivary complex. In rats, this nucleus is composed of a morphologically homogeneous population of GABAergic neurons that receive excitatory input from the contralateral cochlear nucleus and inhibitory input from the ipsilateral medial nucleus of the trapezoid body. SPON neurons provide a dense projection to the ipsilateral inferior colliculus and are thereby capable of exerting profound modulatory influence on collicular neurons. Despite recent interest in the structural and connectional features of SPON, little is presently known concerning the physiological response properties of this cell group or its functional role in auditory processing. We utilized extracellular, in vivo recording methods to study responses of SPON neurons to broad band noise, pure tone, and amplitude-modulated pure tone stimuli. Localization of recording sites within the SPON provides evidence for a medial (high frequency) to lateral (low frequency) tonotopic representation of frequencies within the nucleus. Best frequencies of SPON neurons spanned the audible range of the rat and receptive fields were narrow with V-shaped regions near threshold. Nearly all SPON neurons responded at the offset of broad band noise and pure tone stimuli. The vast majority of SPON neurons displayed very low rates of spontaneous activity and only responded to stimuli presented to the contralateral ear, although a small population showed binaural facilitation. Most SPON neurons also generated spike activity that was synchronized to sinusoidally amplitude-modulated tones. Taken together, these data suggest that SPON neurons may serve to encode temporal features of complex sounds, such as those contained in species-specific vocalizations.

Acoustic Stimulation↗

PubMed2002

Optimizing synaptic architecture and efficiency for high-frequency transmission.

Bursts of neuronal activity are transmitted more effectively as synapses mature. However, the mechanisms that control synaptic efficiency during development are poorly understood. Here, we study postnatal changes in synaptic ultrastructure and exocytosis in a calyx-type nerve terminal. Vesicle pool size, exocytotic efficiency (amount of exocytosis per Ca influx), Ca current facilitation, and the number of active zones (AZs) increased with age, whereas AZ area, number of docked vesicles per AZ, and release probability decreased with age. These changes led to AZs that are less prone to multivesicular release, resulting in reduced AMPA receptor saturation and desensitization. A greater multiplicity of small AZs with few docked vesicles, a larger pool of releasable vesicles, and a higher efficiency of release thus promote prolonged high-frequency firing in mature synapses.

Action Potentials↗

PubMedDate not supplied

Histologic and immunologic observations of viral-induced rhinosinusitis in the mouse.

Viral upper respiratory infection is one of the most common diagnoses made in primary care offices. Although symptoms resolve within 1 week for many patients, a percentage develops rhinosinusitis, and many of these patients are treated with antibiotics. We have developed a model of viral rhinosinusitis using intranasal inoculation of reovirus into mice that were then killed on postinoculation days 2, 4, 7, 10, 14, or 21 and heads were embedded in paraffin for histological and immunohistochemical analyses. Reovirus-like immunoreactivity was noted in the septa and paranasal sinus mucosa in mice as early as day 2, with peak intensity seen on day 4, and scant staining seen on day 7. Complete absence of viral staining was seen by day 10, which corresponded with increased intracellular adhesion molecule 1 immunostaining in the nose. By day 10, a large mucosal influx of B cells was observed, with a moderate influx of macrophages and smaller influx of T cells. By day 14, there was a peak in the number of B cells with a corresponding, but less pronounced peak in T cells, while macrophages began to decline at this point. By day 21, the panel of immune markers returned to near normal levels. The results of this study suggest that the immune system continues to produce a response as long as 2 weeks after clearance of viral antigens. One proposed mechanism for this phenomenon is that local factors such as cytokines are released continually after infection, even in the absence of persistent viruses or bacteria.

Animals↗