Thesis (Ph.D.)--University of California, San Francisco, 2009. / Source: Dissertation Abstracts International, Volume: 71-02, Section: B, page: . Adviser: Graeme W. Davis.

The central nervous system of the cockroach is able to recover following nerve lesions, by specific re-innervation of targets. Some aspects of such regeneration were studied in vitro and in vivo to discover how this is achieved. Neural explants from the cockroach central nervous system were maintained in culture for UP to six months. The effect of various parameters, such as temperature and growth medium composition upon the rate and extent of fibre outgrowth was studied. There was no apparent selectivity in the formation of connections between co-cultured neural or muscular explants, suggesting that the cues necessary for specific re-innervation in vivo may be absent in vitro. Under normal conditions, outgrowth usually began by about five days in culture. The delay before onset of fibre outgrowth, however, was reduced by prior section of nerves in situ two to three weeks before explantation of ganglia into culture. Outgrowth from these nerves which had received a 'conditioning lesion' was observed as soon as 12-24 hours after explantation into culture. Similarly, functional recovery occurred sooner in vivo after equivalent operations: normal function returned to animals more quickly after a second lesion to the same nerve, than after one lesion only. The morphology of an identifiesd motoneurone was studied by intracellular cobalt injection, to assess the effect of maintenance in culture, or of different nerve lesions performed in vivo. Nerve lesions caused changes in the branching pattern of this identified neurone. The extent of change appeared to be determined largely by the overall extent of damage to the nervous system. Direct damage to the cell was not a pre-requisite for changes to occur. In many cases, supernumerary branches entered territory which was normally foreign to the motoneurone. In some areas this growth appeared to be random, while in others sprouts gave the appearance of following paths of degenerating nerve fibres. It is concluded that at least some adult insect neurones are capable of extensive regenerative growth, and of undergoing a high degree of structural modification, both in vivo and in vitro, indicating that some plasticity is a feature of the adult insect nervous system.

1. The giant neurone in the left pedal ganglion of Helisoma trivolvis is homologous with the giant dopamine containing neurone of Planorbis corneus. The neurones have a similar morphology, and both react with glyoxylic acid to produce fluorescence indicative of dopamine. The neurone is referred to as the giant dopaminergic neurone (GDN). 2. Conditions for the extension of neurites and the formation of chemical junctions in culture have been determined for the H. trivolvis GDN. 3. Some electrical properties of the GDN were altered when it was maintained in culture. The peak spike amplitude was increased, action potential half width was decreased and the firing pattern changed. 4. In culture, the GDN formed chemical connections only with neurones with which it was known to form chemical connections in-situ. The chemical connections were of the same sign as those observed in-situ. They formed rapidly within 18 hours, but were not stable and were lost within 48 hours to be replaced by electrical connections. 5. Chemical junctions formed in both directions between the GDN and the large serotonergic neurone (LSN). The direction in which junctions formed could be influenced by plating each neurone out at different times. 6. Local application of dopamine to the axon or axon hillock, but not the soma of the isolated GDN, evoked a fast strongly desensitising, depolarising response. 7. Intracellular perfusion of the GTP analogue GDP-?-S abolished the hyperpolarising effect of dopamine but left the fast depolarising effect intact. 8. Dopamine evoked small unitary outward currents, in outside-out patches prepared from the axon and axon hillock of the isolated GDN. 9. The results suggest that the fast depolarising response to dopamine of the GDN and its follower neurones is directly ligand gated. This is the first evidence of an ion channel that is directly gated by dopamine.

Dopamine is one of a number of neurotransmitter candidates found in the insect CNS, It has been localised in a number of neurones, and others have been shown to respond to the application of dopamine. This study investigates the response of the common inhibitory motoneurone D3 to dopamine, and its ionic basis. The response to dopamine is distinguished pharmacologically from responses to noradrenaline, octopamlne and acetylcholine, all neurotransmitter candidates within the insect CNS, and it is concluded that a receptor specific for dopamine is present on this cell. Finally, this putative dopamine receptor is characterised pharmacologically, and its position relative to the extant classification schemes for mammalian receptors, and its similarity or otherwise to other invertebrate dopamine receptors is discussed.

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No description available.

The neurotransmitter gamma-aminobutyric acid (GABA) stimulates the release of luteinizing hormone (LH) by enhancing gonadotropin-releasing hormone (GnRH) release in the goldfish, Carassius auratus. Activin A is another protein that stimulates the release of LH. Activin A also stimulates the release of GnRH from the rat hypothalamus, but this effect has never been shown in fish. Using real-time RT-PCR, we have shown that an injection of baclofen, a GABAB receptor agonist, into sexually mature goldfish stimulates the expression of activin betaA subunits in the telencephalon and sGnRH in the hypothalamus. Baclofen also inhibits the expression of that activin receptor IIB and IB in the hypothalamus. Immunocytochemical studies show that activin betaA subunits and activin receptors are localised in the olfactory bulb, telencephalon, thalamus, hypothalamus and optic tectum. Activin receptors are colocalised with GnRH fibres in the hypothalamus. This study has provided further insight into the role of activin as a neuroendocrine factor controlling reproduction in the goldfish brain.

Dopamine (DA) is the single most potent inhibitor of luteinizing hormone (LH) release from the fish pituitary and is fundamental to the neuroendocrine control of reproduction in vertebrates. It exerts its functions through DA D1- and D2-specific postsynaptic receptors. In order for DA to be such a potent inhibitor of reproduction, I hypothesized that DA must inhibit multiple LH-stimulatory systems in the brain. I provide the first evidence that a specific DA receptor, the D2 receptor, is alternatively spliced in fish and discuss its significance in terms of the inhibitory tone of DA. A wide-scale assessment of the genes and proteins that are under the regulatory control of DAergic action is provided and begins to elucidate mechanistic pathways that DA may be modulating and showed that D1- and D2-receptor specific agonists modulate different biochemical pathways. It is then shown that DA, acting through the D1 receptor, may be modulating the effects of another neurotransmitter, glutamate, through AMPA-type receptors. Blockage of the D1 receptor resulted in a rapid and pronounced increase of activin betaa transcription and subsequent stimulation with AMPA resulted in a significant increase in isotocin and chicken-type gonadotropin-releasing hormone, concurrently with increased circulating LH levels. The hypothalamic expression of a neuronal stem cell marker, DA cell markers and developmental factors are significantly increased in the days following injection with a specific DA neurotoxin. This provides evidence for DA neuron regeneration in the adult hypothalamus, and is indicative of an intrinsic regenerative capacity of the principle hypophysiotropic LH-inhibitory system for dynamic recovery and maintenance of function after injury. Comprehensive meta-analysis of microarray data identified 268 ESTs that are very likely to be transcriptionally-regulated by DA, indicating the major influence of DA on hypothalamic function. The hypothesis that industrial pollution (pulp and paper mill effluents) inhibits reproduction in the fathead minnow was tested by determining effects on the hypothalamic gene expression. This thesis (1) characterizes the role of DA in neuroendocrine function in fish; (2) identifies a novel mechanism of LH release mediated through DA, and; (3) demonstrates an ecologically-relevant and industrial application of the findings of this thesis.

Music often evokes strong emotions, such as excitement, joy, and nostalgia. These emotions can be highly pleasurable and accompanied by increased physiological arousal. Pleasure-inducing music activates a network of brain regions including the medial prefrontal cortex (mPFC), striatum, and amygdala. In Experiment 1, I explore the neural structures critical for music-evoked pleasure. I hypothesize that individuals with damage to brain regions involved in emotional responses to music (e.g., mPFC, striatum, amygdala) will show a decrease in their pleasurable responses to music after brain injury. Patients from the Iowa Neurological Patient Registry completed questionnaires that assessed current emotional responses to music and changes in emotional responses to music after brain injury. The results provided partial support for the hypothesis, and the most striking loss of musical pleasure (referred to as "music anhedonia") occurred in a patient with damage to the striatum. However, musical pleasure appears to be relatively resistant to brain damage, as music anhedonia was only observed in a few individuals with varying regions of brain damage. Along with strong emotions, music often triggers distant memories. However, the mechanism underlying music-evoked autobiographical memories (MEAMs) has not yet been investigated. Here, I predict that emotion is a central aspect underlying MEAMs. In Experiment 2a, I tested the hypothesis that MEAMs are more emotional and vivid than autobiographical memories evoked by pictures of famous faces. Neurologically normal, healthy adults viewed pictures of famous faces and listened to music while electrodermal activity was recorded. After each stimulus, participants described any memories that were evoked. Supporting my prediction, I found that MEAMs were significantly more vivid than face-evoked memories. In addition, music that evoked memories was accompanied by increased skin conductance responses compared to music that did not evoke memories. In Experiment 2b, I used a neuropsychological approach to test the prediction that neural regions underlying music-evoked emotions are also critical for MEAMs. I tested the hypothesis that individuals with damage to brain regions important for music-evoked emotions (mPFC, amygdala, and striatum) would have impaired MEAMs. Individuals with damage to these regions, brain-damaged comparison subjects (with damage to other regions) and neurologically normal comparison subjects completed the same task as in Experiment 2a. The results indicated partial support for the hypothesis, showing that individuals with mPFC, but not striatal, damage had slightly decreased MEAM vividness. Additionally, individuals with damage to the striatum and mPFC showed a disconnect between emotional ratings and physiological responsiveness. These findings provide important implications for the use of music in therapeutic settings. Since musical reward is predominantly preserved in individuals with brain damage, music can be used to improve mood and affect in clinical populations. In addition, these findings support the use of music as a memory aid in patients with dementia, since music-evoked memories are shown to be more vivid than memories evoked by other cues. Together, these experiments provide partial support for the hypothesis that neural regions important for emotion are also critical for MEAMs, indicating that emotion may be an important aspect underlying music-evoked autobiographical memories.

No description available.