Biomedical subjects

Barbara J Morley

Publications and source records attributed to Barbara J Morley.

5 recordsLinked to original sources

PubMed2005

Nicotinic cholinergic intercellular communication: implications for the developing auditory system.

In this paper, research on the temporal and spatial distribution of cholinergic-related molecules in the lower auditory brainstem, with an emphasis on nicotinic acetylcholine receptors (nAChRs), is reviewed. The possible functions of acetylcholine (ACh) in driving selective auditory neurons before the onset of hearing, inducing glutamate receptor gene expression, synaptogenesis, differentiation, and cell survival are discussed. Experiments conducted in other neuronal and non-neuronal systems are drawn on extensively to discuss putative functions of ACh and nAChRs. Data from other systems may provide insight into the functions of ACh and nAChRs in auditory processing. The mismatch of presynaptic and postsynaptic markers and novel endogenous agonists of nAChRs are discussed in the context of non-classical interneuronal communication. The molecular mechanism that may underlie the many functions of ACh and its agonists is the regulation of intracellular calcium through nAChRs. The possible reorganization that may take place in the auditory system by the exposure to nicotine during critical developmental periods is also briefly considered.

Acetylcholine↗

PubMed2004

Distribution and postnatal development of alpha 7 nicotinic acetylcholine receptors in the rodent lower auditory brainstem.

The distribution and quantity of the alpha 7 nicotinic acetylcholine receptor (nAChR) were mapped in the nuclei of the superior olivary complex, lateral lemniscus, and inferior colliculus in the developing and mature rat brain. Radioactive in situ hybridization and (125)I-alpha-bungarotoxin receptor binding were used to measure alpha 7 transcript and membrane-bound protein, respectively. The highest transcript and protein levels were found in the external nucleus of the inferior colliculus and paraolivary nucleus. More moderate levels of transcript and protein were measured in the ventral, intermediate, and dorsal nuclei of the lateral lemniscus, lateral and medial ventral posterior olivary nuclei, rostral periolivary region, lateral periolivary nucleus, caudal periolivary region, ventral and dorsal trapezoid nuclei, medial superior olive, and the lateral superior olive. Peak receptor expression generally occurred before the onset of hearing. The significant overlap of transcript and protein in these regions suggests that the alpha 7 nAChR is predominantly localized postynaptically on somata or proximal dendrites. In a separate experiment, alpha 7 transcript was quantified in the superior olivary complex, lateral lemniscus, and inferior colliculus of +/+ and null mutant (-/-) mice for the acetylcholinesterase (AChE) gene. The distribution and quantity of alpha 7 nAChR were not different in +/+ and -/- mice, suggesting that AChE may not induce or regulate alpha 7 transcription during the early postnatal period.

Acetylcholinesterase↗

PubMed2004

A phenotype for the alpha 7 nicotinic acetylcholine receptor null mutant.

The alpha7 nicotinic acetylcholine receptor (nAChR) is heavily expressed in the mammalian brain. On a molecular level, the alpha7 nAChR may have a diversity of functions, but it is not known if these molecular events translate into phenotypes. The null mutant mouse is viable and generally normal. Here, we report a phenotype for the alpha7 nAChR null mutant mouse. The alpha7 nAChR is obligatory for the synchronization of an important biological rhythm, the female estrous cycle. The female null mutant mouse has asynchronous estrous cycles and a reduced number of surviving pups. Female null mutants also demonstrate a reliable diversity in phenotype, suggesting an interaction between environment and gene expression. Real-time RT-PCR measurements of the alpha7 mRNA expression in reproductive tissues of wild-type mice suggest that the ovulatory dysfunction in null mutants is probably central in origin.

Animals↗

PubMed2004

Transient expression of acetylcholinesterase in the posterior ventral cochlear nucleus of rat brain.

In this report we partially characterize a pathway projecting to the posterior ventral cochlear nucleus (PVCN) of the rat brain that transiently expresses a high level of acetylcholinesterase (AChE). The AChE-positive axons form a network that envelops a discrete region of the PVCN that includes the octopus cell region and some cells rostral to it. AChE is first detectable by postnatal day 3 (P3), peaks in expression at about P7-10, and is barely detectable in our preparations by P15. We previously reported that neurons in the octopus cell region express high levels of alpha7 nAChR mRNA and alpha-bungarotoxin binding during the same time period. In light microscopic immunocytochemical studies using antibodies to the vesicular acetylcholine transporter (VAChT), we could not identify immunopositive boutons in the developing regions of the PVCN that express high levels of AChE-positive fibers despite distinct punctate labeling in other brain regions. Systematic electron microscopic examination of AChE histochemical staining throughout the PVCN revealed intense labeling of axons, but synaptic sites were devoid of reaction product. The source of the AChE-positive fibers is not known, but the fibers are not auditory nerve axons and probably not collaterals of the olivocochlear bundle.

Acetylcholine↗

PubMed2002

Developmental mRNA expression of the alpha10 nicotinic acetylcholine receptor subunit in the rat cochlea.

A recently discovered alpha10 subunit of the nicotinic acetylcholine receptor (nAChR) family is believed to form a heteromeric receptor with the alpha9 nAChR subunit in auditory hair cells. In the present study, the alpha10 nAChR subunit expression in the developing and adult rat inner ear was analyzed by PCR and localized using isotopic in situ hybridization. Unlike the alpha9 subunit, the alpha10 subunit was not detected at embryonic day 18 (E18). From E21 through postnatal day 15 (P15), the alpha10 subunit was localized over both inner hair cell (IHC) and outer hair cell (OHC) regions, but in the mature cochlea detectable levels of alpha10 mRNA were found only over the OHC region. From E21 through adult ages, there was also a small but consistent basal to apical gradient of alpha10 expression; that is, higher levels in basal regions and lower levels in apical regions. Previously, we detected the alpha9 nAChR subunit over IHCs as early as E18 and throughout adult ages with a clear basal-apical gradient of expression. Our studies raise the question of whether the alpha9 and alpha10 subunits are differentially regulated during embryonic and postnatal development.

Aging↗