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Title: Spinothalamic tract neurons in laminae I, III and IV of the rat : a retrograde neuronal tracing study
Author: Al-Khater, Khulood
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2009
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Abstract:
Ascending pathways in the spinal cord are very important in transmitting sensory information from the periphery to the higher brain centres. The spinothalamic tract represents an important component of these ascending pathways, and it has been traditionally described as the main pathway for conveying nociceptive and thermoceptive information. Spinothalamic neurons are widely distributed within the grey matter. Lamina I represents an important nociceptive zone and provides a significant source of projection neurons, some of which project to the thalamus. A projection from cervical superficial dorsal horn to the posterior triangular thalamic nucleus (PoT) in the rat has recently been identified. The PoT is located at the caudal end of the thalamus and was not included in injection sites in many previous quantitative retrograde tracing studies of the spinothalamic tract. Therefore, one of the reasons to conduct the present study was to estimate the number of the spinothalamic cells in lamina I in rat cervical and lumbar enlargements following injections that target the PoT with or without other thalamic nuclei known to receive input from lamina I. Neurons in this lamina are also known to project to the lateral parabrachial nucleus (LPb) and the periaqueductal grey matter (PAG). Other aims of the study were to quantify neurons in lamina I in the cervical enlargement that project to the LPb and PAG, to determine the proportion of lamina I spinothalamic neurons in lumbar and cervical enlargements that could be labelled from LPb and PAG, and to investigate morphological differences between different projection populations. Recent investigations have identified a group of neurons in lamina I of rat lumbar spinal cord that had large numbers of puncta that were immunoreactive for the glycine receptor-associated protein, gephyrin, and have a very high density of input from glutamatergic axons that contain vesicular glutamate transporter 2 (VGLUT2). These "large gephyrin-coated cells" in the lumbar cord are known to project to the LPb, but it is not yet known whether they project to thalamus and PAG. Therefore, another aim was to determine whether these cells project to these areas and also to analyse the projection pattern of cells of this type in the cervical enlargement. Previous studies have identified a population of large neurons in laminae III and IV of rat spinal cord that express the neurokinin 1 receptor (NK1r) and have prominent dorsal dendrites that enter the superficial laminae. A substantial body of evidence points to the involvement of this population of cells in processing various types of noxious stimulus. Neurons of this type in lumbar enlargement are projection cells and form a major route through which nociceptive information reaches the brain. The proportion of these neurons that project to thalamus was not previously known, and the projection pattern of cells of this type in cervical enlargement has not yet been investigated. Therefore, an additional aim was to elucidate more on the projection patterns of these cells in both enlargements. Various tracers (cholera toxin B subunit, Fluorogold or fluorescent latex microspheres) were injected stereotaxically into thalamus (25 rats), into thalamus and LPb (3 rats), or into thalamus and PAG (4 rats). Rats were perfused after three days and sections from the spinal cord (cervical and lumbar enlargements) were processed immunocytochemically to reveal tracer(s) in lamina I and lamina III/IV neurons, the NK1r, neuronal nuclei and, in some cases, the glycine receptor-associated protein gephyrin. Sections from brains were processed to visualise the injection sites. Results of this study showed that: 1) most lamina I spinothalamic neurons in the C7 and L4 segments could be labelled from injections centred on the PoT; 2) the estimated total numbers of spinothalamic cells in lamina I on the contralateral side of the C7 and L4 segments are 91 and 16 cells, respectively, and this constitutes 2-3% and 0.2% of the total neuronal population in lamina I in the C7 and L4 segments, respectively; 3) the C7 segment contained fewer lamina I spinoparabrachial cells, but a similar number of spino-PAG cells, compared to L4; 4) virtually all spinothalamic lamina I neurons at both cervical and lumbar levels were labelled from LPb and between a third and a half were labelled from PAG; 5) spinothalamic lamina I neurons differed from those labelled only from LPb in that they were generally larger, more often multipolar and (in cervical enlargement) had stronger NK1r-immunoreactivity; 6) ~39% of "large gephyrin-coated cells" in L5 project to the thalamus and this accounts for ~21% of the total thalamic projection from lamina I in this segment, even though these cells constitute only ~2.5% of projection neurons in lamina I; 7) the great majority of "large gephyrin-coated cells" in C6 project to thalamus and LPb, and at both segmental levels, some project to both of these areas; 8) only few "large gephyrin-coated cells" in L5 and some of those in C6 project to PAG; 9) ~84% of the lamina III/IV NK1r-immunoreactive neurons in C6 and C7 and 17 28% of those in L4 and L5 belong to the spinothalamic tract, and these apparently project exclusively to the caudal thalamus, including PoT; 10) most of the large NK1r-immunoreactive lamina III/IV cells at both levels project to LPb, but few were labelled from PAG, and at both segmental levels, some project to both thalamus and LPb. Findings from the present study indicate that the PoT is one of the major targets for neurons in lamina I as well as to the population of the NK1r-immunoreactive neurons in laminae III and IV. Since the PoT projects to the second somatosensory and insular cortices, the present results suggest that these are major targets for information conveyed by both these populations of spinothalamic neurons. In addition, these results confirm that projection neurons have extensive collateral projections, and suggest that different sub-populations of lamina I cell have characteristic patterns of supraspinal projection.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.513043  DOI: Not available
Keywords: RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry ; Q Science (General)
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