by Priscilla, Ka-Yee Chan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 77-100). / Abstract also in Chinese. / ACKNOWLEDGEMENTS --- p.4 / ABSTRACT --- p.5 / ABSTRACT (Chinese) --- p.7 / PUBLICATION --- p.8 / ABBREVIATION --- p.9 / Chapter CHAPTER 1 --- INTRODUCTION --- p.10 / Chapter 1.1 --- Overview of the study --- p.10 / Chapter 1.2. --- Substantia nigra pars reticulata (SNR) --- p.12 / Chapter 1.2.1 --- SNR and the basal ganglia / Chapter 1.2.2 --- GABA neurotransmission in SNR / Chapter 1.2.3 --- SNR and epilepsy / Chapter 1.3 --- GABAb receptors --- p.18 / Chapter 1.3.1 --- GABA receptors / Chapter 1.3.2 --- GABAb receptors and their classification / Chapter 1.3.3 --- Agonists and antagonists of GABAb receptor / Chapter 1.3.4 --- Distribution of GAB AB receptor / Chapter 1.3.5 --- GABAb receptors in epilepsy and the involvement of SNR / Chapter 1.4 --- Cannabinoid receptors --- p.24 / Chapter 1.4.1 --- Cannabinoid receptors and their classification / Chapter 1.4.2 --- Agonists and antagonists of cannabinoid receptor / Chapter 1.4.3 --- Distribution of cannabinoid receptors / Chapter 1.4.4 --- Cannabinoid receptors in epilepsy and the involvement of SNR / Chapter CHAPTER 2 --- METHODS --- p.31 / Chapter 2.1 --- Brain slice preparation and maintenance --- p.31 / Chapter 2.2 --- Experimental set-up --- p.32 / Chapter 2.2.1 --- Visualization of neurones / Chapter 2.2.2 --- Electrophysiological recordings / Chapter 2.2.3 --- Evoked stimulation / Chapter 2.2.4 --- Drug preparation and administration / Chapter 2.3 --- Identification of GAB A and dopamine neurones --- p.36 / Chapter 2.4 --- Data analysis --- p.37 / Chapter 2.4.1 --- Construction of dose-response curve / Chapter 2.4.2 --- Analysis of synaptic currents / Chapter 2.4.3 --- Statistics / Chapter CHAPTER 3 --- RESULTS --- p.39 / Chapter 3.1 --- Basic characteristics of IPSCs in SNR --- p.39 / Chapter 3.1.1 --- Spontaneous and miniature IPSCs / Chapter 3.1.2 --- Evoked IPSCs / Chapter 3.2 --- GABAb receptors in SNR --- p.42 / Chapter 3.2.1 --- Postsynaptic GABAb receptors in SNR neurones / Chapter 3.2.1.1 --- Baclofen-activated postsynaptic response / Chapter 3.2.1.2 --- Effects of GABAb receptor antagonist on IPSCs / Chapter 3.2.2 --- Presynaptic GABAb receptors / Chapter 3.2.3 --- Effects of GAB A uptake blocker / Chapter 3.3 --- Cannabinoid receptors in SNR --- p.51 / Chapter 3.3.1 --- Postsynaptic cannabinoid receptors in SNR neurones / Chapter 3.3.2 --- Presynaptic action of cannabinoids / Chapter CHAPTER 4 --- DISCUSSION and CONCLUSION --- p.55 / Chapter 4.1 --- General properties of IPSCs --- p.55 / Chapter 4.2 --- GABAb receptors in SNR neurones --- p.58 / Chapter 4.2.1 --- Postsynaptic GABAB receptors in SNR neurones / Chapter 4.2.2 --- GABAb component in spontaneous and evoked IPSCs / Chapter 4.2.3 --- Presynaptic GABAb receptors in SNR / Chapter 4.2.4 --- Role of GABA uptake / Chapter 4.3 --- Cannabinoid receptors in SNR neurones --- p.67 / Chapter 4.3.1 --- Postsynaptic cannabinoid receptors in SNR neurones / Chapter 4.3.2 --- Presynaptic cannabinoid receptors in SNR / Chapter 4.4 --- SNR GABAb and cannabinoid receptors - their role in epilepsy --- p.72 / Chapter 4.5 --- Concluding remarks and future direction --- p.75 / REFERENCES --- p.77

by Wu Cheok Wai. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 35-39 (2nd gp.)). / Abstract also in Chinese. / Abstract in English --- p.i / Abstract in Chinese --- p.iii / Acknowledgment --- p.v / Chapter Chapter 1: --- Introduction --- p.1 / Chapter 1.1 --- GABAa Mediated Neurotransmission --- p.1 / Chapter 1.2 --- Determinants of GABAa IPSC Kinetics --- p.3 / Chapter 1.3 --- Detection of the Spontaneous IPSCs --- p.5 / Chapter 1.4 --- The C++ Programming Language --- p.7 / Chapter Chapter 2: --- The Detection Algorithm --- p.11 / Chapter 2.1 --- Overview of the Algorithm --- p.11 / Chapter 2.2 --- Detection of Events --- p.12 / Chapter 2.3 --- Measurement of Parameters --- p.20 / Chapter Chapter 3: --- Performance Evaluation --- p.22 / Chapter 3.1 --- The Automatic Detection Software --- p.22 / Chapter 3.2 --- Performance of the Software --- p.23 / Chapter 3.3 --- Discussion --- p.25 / Chapter Chapter 4: --- Application --- p.28 / Chapter 4.1 --- Introduction --- p.28 / Chapter 4.2 --- Materials and Methods --- p.29 / Chapter 4.3 --- Results --- p.32 / Chapter 4.4 --- Discussion --- p.33 / Reference --- p.35 / Appendix --- p.40

Postnatal handling of rat litters during the first week of life greatly decreases behavioural fearfulness to novelty in the adult offspring. Our first question was to what extent the Benzodiazepine/GABAA receptor complex, a system critical for the expression of fear, might be involved in mediating the observed reduced fearfulness in handled animals (H). Benzodiazepine receptor (BZ) binding was reduced in the amygdala and locus coeruleus (LC), regions important for the expression of fear in non-handled (NH) and maternally separated animals (MS). Moreover, levels of the mRNA for the gamma2 sub-unit of the GABAA receptor complex, which confers high affinity BZ binding, were higher in the amygdaloid nuclei as well as in the LC of handled compared with both NH and MS animals. / Studies with the handling paradigm have lead to the idea that variations mother-pup interactions may actually be the cause of the handling effects. As adults, the offspring of mothers which exhibited high levels of licking/grooming and arched-back nursing (LG-ABN) showed substantially reduced behavioral fearfulness in response to novelty compared to the offspring of low LG-ABN mothers. In addition, the adult offspring of the high and low LGABN mothers showed the same receptor and molecular profiles as H and NH adult offspring. Corticotropin releasing factor (CRF) and alpha2 norepinephrine receptor levels, additional receptor systems thought to be important in the expression of fearfulness, differed in these animals too. Adoption studies give further support to the maternal hypothesis in the finding that the expression mRNA for the gamma2 sub-unit of the GABAA receptor complex can be differentially expressed as a result of different offspring to mother combinations. / Taken together, these findings suggest that early life events (ie: naturally occurring differences in maternal care) during the first few days of life have long-term effects on the development of central neurotransmitter systems, which mediate the expression of fearfulness to novelty.

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