The currents generated by excitatory and inhibitory synapses on motoneurons can be amplified by noradrenalin and serotonin. Both of these neurotransmitters act, and interact, via the same Gq-protein second-messenger system to modulate L-type Ca++, persistent-Na+, and leak K+ channels on motoneuron dendrites. However, noradrenergic and serotonergic synapses only modulate nearby excitatory and inhibitory synapses, so their relative distributions play a major role in the regulation of the overall output of the motoneuron. Moreover, the relative proximity between noradrenergic and serotonergic synapses may allow their individual effects to combine nonlinearly when co-activated, thereby regulating the magnitude of the amplification. The goal of the present study is to determine whether the distributions of noradrenergic and serotonergic synapses are biased along motoneuron dendritic trees. The dendritic trees of five intracellularly stained feline splenius motoneurons were reconstructed. On them were plotted the locations of noradrenergic and serotonergic contacts, as determined by immunohistochemistry. The distribution of noradrenergic contacts was moderately biased both dorsally and distally in all five cells. Serotonergic contacts on the same neurons showed a moderate ventral bias. These findings suggest that excitatory and inhibitory inputs located dorsally and/or distally are preferentially amplified by noradrenergic synapses. Also, those synapses which are located ventrally are favorably amplified by serotonergic synapses. Both serotonergic and noradrenergic contacts are strongly biased towards innervation along small diameter (<2μm) dendrites. The relative distributions between serotonergic and noradrenergic contacts have also been analyzed for all five cells. There was a bias towards minimizing the distance between like contacts (NE to NE and 5-HT to 5-HT). This increases the likelihood of interaction within populations when contacts are co-activated. Conversely, the distances between neighbouring noradrenergic and serotonergic contacts (NE to 5-HT and 5-HT to NE) were biased towards greater separation. This decreases the likelihood of interaction between populations when contacts are co-activated. In summary, these findings suggest that noradrenalin and serotonin, having different location biases along the dendritic tree, will amplify some synapses in a biased manner. Additionally, like synapses may work in a coordinated manner with respect to their relative proximity. Coordination between noradrenergic and serotonergic synapses is less likely. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2008-09-29 09:59:38.799

Thesis (Ph. D.)--University of Texas at Austin, 2007. / Vita. Includes bibliographical references.

Thesis (MSc(R)) - University of Glasgow, 2007. / MSc(R) thesis submitted to the Department of Mathematics, Faculty of Information and Mathematical Sciences, University of Glasgow, 2007. Includes bibliographical references.

The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on September 15, 2009). Thesis advisor: Satish S. Nair. Includes bibliographical references.

Thesis (M. Sc.)--Carleton University, 2001. / Includes bibliographical references (p. 91-98). Also available in electronic format on the Internet.

Thesis supervisor: Joshua A. Weiner. Includes bibliographic references (p. 108-126).

Thesis (Ph. D.)--University of Queensland, 2003. / Includes bibliographical references.

Thesis (Ph.D.)--Hong Kong University of Science and Technology, 2007. / Includes bibliographical references (leaves 239-270). Also available in electronic version.

Information is transferred between neurons in the brain via electrochemical transmission at specialized cell-cell junctions called synapses. These structures are far from being static, but rather are influenced by plasticity mechanisms that alter features of synaptic transmission as means to build routes of information flow in the brain. Hebbian forms of synaptic plasticity – long-term potentiation and long-term depression – have been well studied and are considered to be the cellular basis of learning and memory, although their positive feedback nature is prone to instability. Neurons are also endowed with homeostatic mechanisms of synaptic plasticity that act to stabilize neural network functions by globally tuning synaptic drive. Precisely how neurons orchestrate this adaptive homeostatic response and how it influences Hebbian forms of synaptic plasticity, however, remains only partially understood. Using a combination of whole-cell electrophysiology, two-photon imaging and glutamate uncaging in organotypic hippocampal slices, I have expanded upon the known repertoire of homeostatic mechanisms that increase excitatory synaptic drive when CA1 hippocampal neurons experience a prolonged period of diminished activity. I found that the subunit composition of AMPA and NMDA receptors, the two major glutamate receptor subtypes at excitatory synapses, are altered which, in addition to increasing synaptic strength, are predicted to change the signaling and integrative properties of synaptic transmission. Moreover, I found that the amount of glutamate released from presynaptic terminals during evoked-transmission is enhanced and that this mechanism might, in part, underlie the uniform cell-wide homeostatic increase in synaptic strengths. Lastly, I found that homeostatic strengthening of synaptic transmission reduced the potential for CA1 synapses to exhibit long-term potentiation, and that this was caused by altered presynaptic release dynamics that impeded plasticity induction. Together, this work highlights several mechanistic strategies employed by neurons to increase excitatory synaptic drive during periods of activity deprivation which, in addition to balancing cellular excitability, alters the metaplastic state of synapses.

To answer whether the mammalian retinotectal pathway is modifiable in the adult, an attempt was made to induce long-term potentiation (LTP) in retinal synapes in the superior colliculus (SC) of the adult rat, in vivo. Extracellular field potentials were recorded in the primary retinotectal afferent zone of the rat superior colliculus while electrically stimulating the optic chiasm. Induction of LTP in this primary visual pathway was attempted using a wide range of stimulus parameters. However, LTP was not observed. Iontophoretic application of bicuculline methiodide, before and during trains of stimuli, did not facilitate LTP in the rat SC. The broad spectrum glutamatergic antagonist, kynurenic acid, greatly reduced the size of the field potentials. This supports suggestions that retinotectal neurotransmission may be mediated by excitatory amino acids. An N-methyl-D-aspartate (NMDA) glutamate receptor mediated contribution to synaptic transmission in the evoked field potential was not evident. Iontophoretic application of the NMDA receptor selective antagonist 2-amino-5-phosphonovaleric acid (APV) had no effect on the field potentials. Even in the presence of bicuculline, there was no evidence for an NMDA component in the field potential response. The non-NMDA glutamate receptor antagonist, 6-cyano-7-nitroquinoxa-line-2,3-dione (CNQX), did not affect the evoked potentials. These data suggest that LTP was not observed in the retinotectal pathway due to several factors that may include: a loss of visual plasticity in the adult rat following the critical period, absence of necessary modulation factors and insufficient NMDA receptor mediated synaptic transmission. / Medicine, Faculty of / Graduate