Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 9 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 7 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 4 uppsatser.

Historically, there have been two lines of research on mammalian hippocampus. The first one is concerned with the role of hippocampus in formations of new memories and owes its origin to the seminal study by Brenda Milner and William Scoville of a single memory disorder patient, widely known as H.M. The second line of research views the hippocampus as the brain area concerned with orienting and navigating in space. It started with John O’Keefe’s discovery of place cells, pyramidal neurons in the CA3 area of hippocampus, that fire when the animal enters a particular place in its environment. I argue that both lines of discoveries seem to be consistent with a more general view of hippocampus as a brain area strongly involved in the integration of sensory, and possibly internal, information. The first part of the thesis presents an investigation of the effect of limited connectivity constraint on the model network in the framework of pattern classification. It is shown that feed-forward neural classifiers with numerous long range connections can be replaced by networks with sparse feed-forward connectivity and local recurrent connectivity without sacrificing the classification performance. The limited connectivity constraint is relevant for most biological networks, and especially for the hippocampus. The second part describes a decoding analysis from the calcium signal recorded in mouse dentate gyrus. The animal’s position can be decoded with approximately 10cm accuracy and the neural representation of position in the dentate gyrus have close to maximal dimensionality. The analysis also suggests that cells with single firing field and cells with multiple firing fields contribute approximately equal amount of information to the decoder.

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by Diana Robertson-Dunn. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 123-132). / Bibliography --- p.viii / Summary --- p.ix / List of Tables --- p.xi / List of Figures --- p.xi / Chapter Chapter One --- Introduction / Chapter 1.1. --- Cerebral asymmetry --- p.1 / Chapter 1.2. --- Functional asymmetry / Chapter 1.2.1. --- Cerebral dominance and laterality --- p.2 / Chapter 1.2.2. --- Speech --- p.2 / Chapter 1.2.3. --- Handedness --- p.3 / Chapter 1.3. --- Morphological asymmetry --- p.4 / Chapter Chapter Two --- Literature review and aim of the research / Chapter 2.1. --- Scope of the literature search --- p.6 / Chapter 2.2. --- Asymmetries of the cerebral hemispheres / Chapter 2.2.1. --- Introduction --- p.6 / Chapter 2.2.2. --- Weight assessments at post-mortem --- p.6 / Chapter 2.2.3. --- Volume assessments at post-mortem --- p.7 / Chapter 2.2.4. --- Volume assessments from CT and MR images --- p.8 / Chapter 2.2.5. --- Summary --- p.11 / Chapter 2.3. --- Asymmetries of the temporal lobes and the Sylvian fissures / Chapter 2.3.1. --- Introduction --- p.12 / Chapter 2.3.2. --- Asymmetries identified at post-mortem --- p.12 / Chapter 2.3.3. --- Asymmetries identified from arteriograms --- p.17 / Chapter 2.3.4. --- Asymmetries identified on CT and MR images --- p.18 / Chapter 2.3.5. --- Summary --- p.21 / Chapter 2.4. --- Asymmetries of the occipital and frontal lobes / Chapter 2.4.1. --- Introduction --- p.22 / Chapter 2.4.2. --- Asymmetry of the occipital lobes --- p.22 / Chapter 2.4.3. --- Asymmetry of the frontal lobes --- p.24 / Chapter 2.4.4. --- Asymmetries of both occipital and frontal lobes in vitro --- p.26 / Chapter 2.4.5. --- Asymmetries of both occipital and frontal lobes in vivo --- p.28 / Chapter 2.4.6. --- Summary --- p.35 / Chapter 2.5. --- Reported levels of left handedness / Chapter 2.5.1. --- Introduction --- p.37 / Chapter 2.5.2. --- Worldwide assessment of handedness --- p.37 / Chapter 2.5.3. --- Use of left hand for writing --- p.39 / Chapter 2.5.4. --- Use of the left hand for writing amongst Chinese in Taiwan and Hong Kong --- p.39 / Chapter 2.5.5. --- Summary --- p.41 / Chapter 2.6. --- Reported differences amongst Chinese and other racesin behavioural and morphological asymmetries / Chapter 2.6.1. --- Introduction --- p.41 / Chapter 2.6.2. --- Racial differences of brain morphology in vitro --- p.42 / Chapter 2.6.3. --- Racial differences of brain morphology in vivo --- p.42 / Chapter 2.6.4. --- Racial differences relating to speech --- p.44 / Chapter 2.6.5. --- Chinese attitudes to use of the left and right hands --- p.44 / Chapter 2.6.6. --- Summary --- p.44 / Chapter 2.7. --- Choice of method / Chapter 2.7.1. --- Choice of CT for morphological brain measurements --- p.45 / Chapter 2.7.2. --- Choice of linear measurements to assess morphological asymmetries --- p.46 / Chapter 2.7.3. --- Selection of subjects for handedness --- p.47 / Chapter 2.7.4. --- Selection of method for handedness assessment --- p.47 / Chapter 2.8. --- Justification for this research --- p.48 / Chapter 2.9. --- Aim and objectives of the research / Chapter 2.9.1. --- Aim of the research --- p.49 / Chapter 2.9.2. --- Objectives of the research --- p.50 / Chapter Chapter Three --- Methods / Chapter 3.1. --- Measurements of the cerebral hemispheres / Chapter 3.1.1. --- Selection of subjects --- p.51 / Chapter 3.1.2. --- Computed tomographic equipment used --- p.51 / Chapter 3.1.3. --- Exposure factors and pixel size --- p.52 / Chapter 3.1.4. --- Position of the subject for routine brain scan --- p.53 / Chapter 3.1.5. --- Exclusion criteria --- p.54 / Chapter 3.1.6. --- Measurements of the frontal and occipital lobes --- p.54 / Chapter 3.1.7. --- Measurements of the mid-cerebral region --- p.56 / Chapter 3.1.8. --- Division of subjects by age --- p.57 / Chapter 3.1.9. --- Reproducibility of width measurements --- p.58 / Chapter 3.1.10. --- Decimal places --- p.59 / Chapter 3.1.11. --- Assumptions --- p.59 / Chapter 3.2. --- Assessment of handedness in three age groups / Chapter 3.2.1. --- Rational behind choice of three groups --- p.63 / Chapter 3.2.2. --- Students aged 19-22 years --- p.64 / Chapter 3.2.3. --- Children aged 6-7 years --- p.64 / Chapter 3.2.4. --- Children aged 4-5 years --- p.65 / Chapter 3.3. --- Analysis of data / Chapter 3.3.1. --- Distribution of width measurements --- p.65 / Chapter 3.3.2. --- The affect of age on the data --- p.66 / Chapter 3.3.3. --- Asymmetry of both frontal and occipital lobes --- p.66 / Chapter 3.3.4. --- Skew Index --- p.66 / Chapter 3.3.5. --- "Significance of ""Positive skew"" and ""Negative skew""" --- p.67 / Chapter 3.3.6. --- Analysis of data for Skew index --- p.69 / Chapter Chapter Four --- Results / Chapter 4.1. --- "Distribution of the width measurements from left and right sides of the occipital,frontal and mid-cerebral regions" / Chapter 4.1.1. --- Introduction --- p.70 / Chapter 4.1.2. --- The mid-cerebral regions --- p.70 / Chapter 4.1.2.1. --- Distribution of widths from the left mid-cerebral region --- p.71 / Chapter 4.1.2.2. --- Distribution of widths from the right mid-cerebral region --- p.72 / Chapter 4.1.2.3. --- Comparison of left and right widths --- p.73 / Chapter 4.1.3. --- The frontal lobes --- p.74 / Chapter 4.1.3.1. --- Distribution of widths from the left frontal lobe --- p.74 / Chapter 4.1.3.2. --- Distribution of widths from the right frontal lobe --- p.75 / Chapter 4.1.3.3. --- Comparison of left and right widths --- p.76 / Chapter 4.1.4. --- The occipital lobes --- p.77 / Chapter 4.1.4.1. --- Distribution of widths from the left occipital lobe --- p.77 / Chapter 4.1.4.2. --- Distribution of widths from the right occipital lobe --- p.78 / Chapter 4.1.4.3. --- Comparison of left and right widths --- p.79 / Chapter 4.1.5. --- Summary of the means and standard deviations of widths --- p.80 / Chapter 4.1.6. --- Correlation between left and right sides --- p.81 / Chapter 4.1.7. --- Correlation of size of regions with age --- p.81 / Chapter 4.1.8. --- Summary --- p.82 / Chapter 4.2. --- Measurements examined as a function of age / Chapter 4.2.1. --- The mid-cerebral regions --- p.83 / Chapter 4.2.1.1. --- The left mid-cerebral region of all age groups --- p.83 / Chapter 4.2.1.2. --- The right mid-cerebral region of all age groups --- p.85 / Chapter 4.2.2. --- The frontal lobes --- p.86 / Chapter 4.2.2.1. --- The left frontal lobe of all age groups --- p.86 / Chapter 4.2.2.2. --- The right frontal lobe of all age groups --- p.87 / Chapter 4.2.3. --- The occipital lobes --- p.88 / Chapter 4.2.3.1. --- The left occipital lobe of all age groups --- p.88 / Chapter 4.2.3.2. --- The right occipital lobe of all age groups --- p.89 / Chapter 4.2.4. --- Summary --- p.90 / Chapter 4.3. --- Asymmetry of the frontal and occipital lobes and Skew Index / Chapter 4.3.1 --- Asymmetry of the frontal and occipital lobes --- p.91 / Chapter 4.3.2 --- Introduction to 'Skew index' --- p.92 / Chapter 4.3.3. --- Positive Skew 226}0ب and 226}0بNegative Skew' --- p.93 / Chapter 4.3.4. --- Distribution of 'Skew index' --- p.95 / Chapter 4.3.5. --- Skew index' as a function of age --- p.96 / Chapter 4.3.5.1. --- Distribution of 226}0بSkew index' of subjects aged 0-9 years (group 1) --- p.96 / Chapter 4.3.5.2. --- Distribution of 'Skew index' of subjects aged 10-19 years (group 2) --- p.97 / Chapter 4.3.5.3. --- Distribution of 'Skew index' of all subjects divided by decade (groups 1-9) --- p.98 / Chapter 4.3.6. --- Summary --- p.99 / Chapter 4.4. --- Handedness --- p.100 / Chapter Chapter Five --- Discussion / Chapter 5.1. --- Morphological asymmetries of the brain / Chapter 5.1.1. --- Asymmetry of the frontal and occipital lobes --- p.101 / Chapter 5.1.2. --- Asymmetry of the temporal lobes --- p.103 / Chapter 5.1.3. --- Skew of the cerebral hemispheres --- p.103 / Chapter 5.2. --- "Findings from the younger age groups, aged under 20 years" / Chapter 5.2.1. --- Width measurements from subjects aged under 10 years --- p.104 / Chapter 5.2.2. --- Skew measurements of subjects aged under 10 years --- p.105 / Chapter 5.2.3. --- Width measurements of subjects aged from 10 to 19 years --- p.106 / Chapter 5.2.4. --- Skew measurements of subjects aged from 10 to 19 years --- p.106 / Chapter 5.3. --- Findings from the adults aged from 20 to 79 years / Chapter 5.3.1. --- Size of the cerebral regions --- p.107 / Chapter 5.3.2. --- Skew measurements of subjects aged from 20 to 79 years --- p.107 / Chapter 5.4. --- Findings from the oldest adults aged over 80 years / Chapter 5.4.1. --- An atypical group of subjects --- p.107 / Chapter 5.4.2. --- Size of the cerebral regions --- p.108 / Chapter 5.4.3. --- Cerebral skew in subjects aged over 80 years --- p.109 / Chapter 5.5. --- "Limitations, problems, bias, artefacts and main weakness" / Chapter 5.5.1. --- Limitations of the occipital and frontal measurements --- p.111 / Chapter 5.5.2. --- Linear measurements and possible limitations --- p.111 / Chapter 5.5.3. --- Problems encountered with cerebral measurements --- p.112 / Chapter 5.5.4. --- Potential bias in selection of subjects for assessing morphological asymmetry of the brain --- p.113 / Chapter 5.5.5. --- Potential source of error from CT artefacts --- p.113 / Chapter 5.5.6. --- Main weakness of this study --- p.113 / Chapter 5.6. --- Handedness / Chapter 5.6.1. --- Cerebral asymmetries --- p.114 / Chapter 5.6.2. --- Numbers of left-handers amongst the Chinese --- p.114 / Chapter 5.6.3. --- Left handedness amongst the Chinese in Taiwan --- p.114 / Chapter 5.6.4. --- Comparison of handedness amongst different races --- p.115 / Chapter 5.6.5. --- Biasing influences on Chinese children at school --- p.116 / Chapter 5.6.6. --- Biasing influences on Chinese children at home --- p.117 / Chapter 5.6.7. --- Handedness in two generations --- p.117 / Chapter 5.6.8. --- Potential bias in selection of subjects for assessing handedness --- p.118 / Chapter 5.6.9. --- Summary of results of handedness --- p.118 / Chapter 5.7. --- Extensions of the study / Chapter 5.7.1. --- Assessment of left-handedness amongst Chinese of Hong Kong --- p.119 / Chapter 5.7.2. --- Establishment of the association between handedness in the population and morphological brain asymmetry --- p.119 / Chapter Chapter Six --- Conclusion / Chapter 6.0 --- Conclusion --- p.121 / References --- p.123 / Acknowledgements --- p.133

The glycine receptor (GlyR) is the major inhibitory ligand-gated ion channel in the brainstem and spinal cord. It is a member of the Cys-loop superfamily of ligand-gated ion channels that includes serotonin-3, GABA[subscript A] and nicotinic acetylcholine (nAChR) receptors. Individual subunits are comprised of a large extracellular N-terminal agonist binding domain, four transmembrane (TM) segments and a large cytoplasmic loop between TM3 and TM4, containing phosphorylation sites (Brejc et al. 2001, Unwin, 2005). These receptors are pentameric in structure, with the TM2 region of each subunit contributing to the formation of a central ion pore (Lynch 2004). While the TM2-3 linker region has been hypothesized to be important for signal transduction thoughout the Cys-loop family, the precise structure and function of this region is unclear. We hypothesized that the TM2-3 linker region is a point of connection between subunits. We used disulfide bond trapping to show that the TM2-3 is able to interact with adjacent subunits and plays a critical role in signal transduction. In addition, we provide experimental evidence that the structure of the TM2-3 linker region in the [alpha]1 GlyR is a [beta]-sheet. We next sought to determine the role of the TM2-3 linker region in allosteric modulation. Using two-electrode voltage clamp electrophysiology we found that the TM2-3 linker can determine the direction of modulation without affecting modulator binding. Finally, we wanted to determine if a single alcohol and anesthetic binding site could be occupied to prevent EtOH molecules from binding. Using a combination of thiol reagents and disulfide bond trapping we show that a residue previously identified as important for the binding of alcohols and anesthetics interacts within the pore. We were unable to increase the volume at residue-267 such that EtOH was unable to bind, suggesting that EtOH may have more than one binding pocket. Together, these findings suggest that the TM2-3 linker plays a critical role in signal transduction and receptor modulation providing a foundation for future work on this region in the GlyR. / text

published_or_final_version / abstract / toc / Zoology / Doctoral / Doctor of Philosophy