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A sensitive and reproducible double antibody radioimmunoassay technique, requiring 50ul of unknown serum or plasma per assay tube, is described for use with 125I and rabbit anti-rat LH serum. The assay system was applied to the study of LH secretion in rats under both normal and experimentally manipulated conditions. Particular attention was focussed upon comparison of circulating LH levels in conscious, unstressed animals with those in anaesthetized animals, with or without surgical stress. Thereafter, the effects of acoustic stimulation and of exogenous LRH administration were studied in conscious and anaesthetized animals. Urethane anaesthesia exerted a profound effect upon the LR-secretory response to exogenous LRH in male rats. Available evidence suggests that the blood sampling method, surgical stress and anaesthesia are each capable of significantly influencing LH secretion, thereby emphasizing the value of studies using conscious, unstressed animals. While a direct effect of urethane on the pituitary gland cannot be excluded, attention is drawn to the possible mediation of a urethane-sensitive inhibitory influence in the mechanism controlling LH secretion in the rat.

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Dispersal of cotton rats was examined over an annual cycle of abundance by removal trapping in pine flatwoods. All cotton rats live-trapped at biweekly intervals on two 0.49 ha grids were removed, whereas rats on an adjacent control grid were tagged an released alive on site. The null hypothesis was that dispersing cotton rats would represent a random sample of sex and weight (age) classes from source populations, e.g. the control grid. Likewise, it was assumed that dispersal rates would be proportional to numerical changes in abundance on the control grid. Dispersing animals were clearly most prevalent on the removal grids during November and December 1979 when numbers of rats on the control grid were increasing. Breeding ceased in December and fewer animals dispersed between January and May. The cumulative number of individual animals captured or removed from the study grids (control and removals) was remarkably similar. The proportion of individuals removed according to weight class was not significantly different among grids. Sex ratios of rats on the control and removal grids were not different from 50:50 (P > 0.05). The conclusion is that dispersing cotton rats represented a cross-section of age groups and sexes. The results support the rank-order template hypothesis as the dispersal strategy of the cotton rat. Genetic and behavioral differences between dispersers and source populations could not be discriminated with the methodology employed.

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Information is believed to be stored in the brain by constructing new neural circuits, and these circuits are shaped by changes in the strength of the synaptic connections between the neurons making up the circuit. According to most theories of memory, new circuits can be formed by either increasing or decreasing the strength of synaptic connections. Bidirectional modifications in synaptic efficacy are also central components in recent computer simulations of learning and memory. While long-term potentiation (LTP) has been the focus of extensive research into the mechanisms underlying information storage in the mammalian brain, long-term depression (LTD) and depotentiation, its depressive counterparts, have not. Furthermore, most of the LTD research has involved the use of anaesthetized animals and in vitro slice preparations, making it more difficult to determine the role of this synaptic phenomenon in learning and memory in the intact behaving animal. This thesis provides the first detailed examination of: 1) the induction and decay of both LTD and depotentiation in the neocortex of the awake, freely moving animal; 2) the effects of N-methyl D-Aspartate receptor (NMDAR) blockade on the induction of LTD, LTP, and depotentiation (NMDA receptor activation is known to play a major role in most forms of LTP); and 3) the interactions between these synaptic phenomena. LTD was expressed as a significant reduction in the amplitude of both short and long-latency field potential components. Depotentiation was expressed as a long lasting decrease in the amplitude of a previously enhanced late component. LTD was found to be greater in magnitude and longer lasting when the conditioning stimulation was repeated. However, unlike LTP induction, the conditioning stimulation was equally effective whether spaced over hours or days. NMDA receptor antagonism blocked LTP induction and instead produced a depression effect similar to LTD. Unlike LTP, LTD and depotentiation were found to be NMDAR-independent in the neocortex of the freely moving rat. LTP and LTD are both reversible phenomena and LTD-inducing stimulation can modulate the effects of LTP-inducing stimulation. LTD-inducing stimulation, when delivered following to LTP-inducing stimulation, attenuates the induction rate for potentiation. LTD and depotentiation may play important roles in the ongoing experience-induced modification of neuronal connectivity. Furthermore, these results are consistent with the hypothesis that potentiation and depression reflect the physiological instantiation of a bidirectional learning rule. / Thesis / Doctor of Philosophy (PhD)

Lactate removal by inactive skeletal muscle was investigated using an isolated rat hindlimb perfusion model under conditions simulating recovery from maximal exercise. The purpose of this investigation was threefold: 1) to quantify the contributions of the oxidative, glyconeogenic, and triacylgylcerol (TG) synthesis pathways to lactate (La) removal, 2) to examine differences in La removal patterns in inactive skeletal muscle of various fiber types, and 3) to investigate the possible mechanisms for La and H⁺ removal by inactive muscle. Male Sprague-Dawley rats were perfused for 60 min, at rest with either a normal perfusate (NP) (N = 8) or a lactacidotic perfusate (LP) (N = 8). The LP perfusate was characterized by elevated concentrations of La (11.0 mMol), K⁺ (7.88 mMol), and hemoglobin (16.7 g·dl⁻¹) and a decreased pH (7.15). Arterial and venous perfusate and soleus (SOL), plantaris (PLT), and white gastrocnemius (WG) muscles were analyzed for various metabolite and ion concentrations. Analysis revealed increased rates of La uptake, glycerol release and C0₂ output in the LP versus the NP group. No difference was observed for O₂ uptake or glucose uptake between the two groups. Tissue anajysis revealed no significant change in muscle ATP, CP, glycogen, pyruvate, F-6-P or TG concentration pre versus post perfusion in both LP and NP groups. Significant increases were found in muscle La concentration (pre vs post and LP vs NP), with SOL having the highest concentration followed by PLT and WG. Muscle [F-1 ,6-diP], F-1 ,6-diP /F-6-P and pyruvate/F-1 ,6-diP ratios were elevated following LP perfusion indicating glyconeogenic inhibition. Muscle glucose levels decreased in the NP but not LP group, indicating a possible shift in substrate utilization in the LP group. In the LP group, total calculated La uptake by the 3 muscles was 61.0 umole, with 14% accumulating as tissue La post perfusion. Of the remaining 86%, 12-33% could be accounted for by oxidative metabolism, and 5-7% may have been involved in glycerol release. The remaining 60-75% was unaccounted for, but was hypothesized to have been involved in carbon cycling along the glycolytic/glyconeogenic pathway and/or in TG/FFA substrate cycling. No evidence was found of net glycogen synthesis from La. Increased H⁺ and K⁺ influx and HCO₃⁻ efflux were observed in response to lactacidotic perfusion. Sodium and Cl⁻ exchange patterns showed a net influx over 60 min of LP perfusion. Data from the ionic flux of the various strong ions and non-volatile H⁺ suggested that La is transported into inactive skeletal muscle by various mechanisms, including HLa diffusion, La/H⁺ cotransport, and possibly La/Cl⁻ exchange. The data also suggested that a number of regulatory mechanisms are activated in rat skeletal muscle to maintain intracellular [H⁺] and membrane potential during lactacidotic perfusion. From this investigation it was concluded that, in inactive muscle of the isolated rat hindlimb perfused for 60 min with a lactacidotic perfusate, patterns of La uptake and metabolic elimination are different from those previously observed for active muscle. The metabolic fates of La appear to be related to the ionic disturbances associated with La and H⁺ influx into inactive muscle. The net ionic movements across the inactive hindlimb appear to be related to the preferred metabolic pathways of La elimination, but whether or not a direct cause and effect relationship exists cannot be stated conclusively. / Thesis / Master of Science (MSc)