It is assumed that plasticity involving up-and down regulation of synaptic strength (i.e., long-term potentiation, LTP; long-term depression, LTD) mediates learning and memory processes. Typically, high-frequency stimulation (HFS) of afferent fibers results in LTP, while low-frequency stimulation (LFS) elicits LTD. In stark contrast to this “HFS- LTP vs. LFS-LTD” dogma, the present thesis characterizes a novel form of LFS-induced LTP in the septohippocampal system. The first set of experiments show that alternating, single pulse stimulation (1 Hz) of the medial septum (MS) and CA3 hippocampal (H) commissural fibres results in a long-lasting potentiation of field excitatory postsynaptic potentials (fEPSPs) in CA1 of urethane-anesthetised rats (MS-H-LTP). MS-H LTP is long lasting (>5 h), requires a specific inter-stimulus interval of 1 s between MS and CA3 stimulation, saturates with repeated stimulation episodes and depends on NMDA receptor activation. In the third chapter (review) I suggest that LFS protocols may more accurately mimic some oscillatory activity patterns (~ 1Hz) present in hippocampal and neocortical circuits during sleep-related memory consolidation. Moreover, I compare the mechanisms underlying classical, HFS-LTP to those mediating MS-H LTP as well as several other types of LFS-LTP in the hippocampus and amygdala in vitro. Subsequently, I investigated cellular mechanisms of MS-H LTP and their similarity to classical HFS-LTP via drug application at the CA1 recording site and showed that MS-H LTP depends on protein kinase A and protein synthesis. This surprising similarity between mechanisms mediating HFS-LTP and MS-H LTP was further supported by occlusion experiments whereby LFS and HFS, delivered to the same animal, competed for the available synaptic potentiation of CA3-CA1 synapses. The final experiments showed that MS-H LTP is compromised in early aged rats, while similar levels of potentiation are expressed in the juvenile and adult hippocampus. Interestingly, MS-H LTP could not be induced (i.e., was occluded) 3 h after training on the hidden platform version of the Morris water maze, while it was unaltered at 8 and 24 h intervals. This thesis characterizes a novel form of hippocampal plasticity at the cellular, synaptic and behavioural level and suggests that LFS-LTP may mediate processes of sleep-related memory consolidation. / Thesis (Ph.D, Neuroscience Studies) -- Queen's University, 2010-10-04 11:35:21.288

Synaptic plasticity reflects the capacity of synapses to undergo changes in synaptic strength and connectivity, and is highly regulated by age and sensory experience. This thesis focuses on the characterization of synaptic plasticity in the primary auditory cortex (A1) of rats throughout development and following sensory deprivation. Initial experiments revealed an age-dependent decline in plasticity, as indicated by reductions in long-term potentiation (LTP). The enhanced plasticity of juvenile rats appeared to be mediated by NR2B subunits of the N-methyl-d-aspartate receptor (NMDAR), as NR2B antagonist application reduced LTP to adult-like levels in juveniles, yet had no effect in adults. The importance of sensory experience in mediating plasticity was revealed in experiments using white noise exposure, which is a sensory deprivation technique known to arrest cortical development in A1. Notably, adult rats reared in continuous white noise maintained more juvenile-like levels of LTP, which normalized upon subsequent exposure to an unaltered acoustic environment. The white noise-induced LTP enhancements also appeared to be mediated by NR2B subunits, as NR2B antagonists reversed these LTP enhancements in white noise-reared rats. Given the strong influence that sensory experience exerts on plasticity, additional experiments examined the effect of shorter episodes of white noise exposure on LTP in adult rats. Exposure to white noise during early postnatal life appeared to “prime” A1 for subsequent exposure in adulthood, resulting in enhanced LTP. The necessity of early-life exposure was evident, as repeated episodes of white noise in adulthood did not enhance plasticity. In older rats that typically no longer express LTP in A1, pharmacological methods to enhance plasticity were explored. Moderate LTP was observed in older rats with cortical zinc application, which may act through its antagonism of NR2A subunits of the NMDAR. Additionally, current source density and cortical silencing analyses were conducted to characterize the distinct peaks of field postsynaptic potentials recorded in A1, with the earlier and later peaks likely representing thalamocortical and intracortical synapses, respectively. Together, this thesis emphasizes the critical role of sensory experience in determining levels of cortical plasticity, and demonstrates strategies to enhance plasticity in the mature auditory cortex. / Thesis (Ph.D, Neuroscience Studies) -- Queen's University, 2011-01-11 14:53:57.677

Muscle performance is partially a consequence of its recent contractile history. Postactivation potentiation (PAP) can occur after muscle contractions and leads to enhanced neuromuscular performance. The purpose of this dissertation was to explain the relationship between muscle factors (twitch potentiation, TP) and neural factors (reflex potentiation, RP) contributing to overall PAP following a non-fatiguing volitional muscle contraction. The tibial nerves of fifteen resistance trained volunteers (eleven men, four women) were stimulated intermittently at supramaximal (Mmax) and submaximal (Hmax) intensities for 20 minutes on separate days under three conditions: rest (Control); after a after a 10 second maximum voluntary isometric contraction (MVIC) of the plantarflexors; and after a low frequency fatigue protocol prior to the MVIC. Plantarflexion isometric torque and rate of force development (RFD), and soleus and gastrocnemius EMG Hmax/Mmax ratios, were analyzed. Both experimental conditions resulted in TP at 10 seconds post-MVIC compared to the control condition. The two experimental conditions were not different for any measure. Torque and RFD at Hmax (overall PAP) were highest at 3 and 4.5 minutes post MVIC, respectively, but were not significantly different from the control condition. EMG values generally were insignificantly increased in the experimental conditions versus the control condition. Mmax torque and RFD significantly contributed to Hmax torque and RFD at 20 seconds, Hmax peak, and 20 minute post-MVIC time points. The soleus significantly contributed to Hmax torque at 20 seconds and 20 minutes post-MVIC, and Hmax RFD at 20 seconds, 4.5 minutes, and 20 minutes post-MVIC. The results of this study suggest that both muscle and neural factors play a significant role in overall PAP, and that neural factors may play a more meaningful role in RFD potentiation than torque potentiation.

No description available.

The rapidly increasing emergence of antibiotic resistance amongst pathogenic bacteria is a major clinical and public health problem. The increase in resistant pathogens, accompanied with the small number of new antibiotics introduced in recent years, has limited the number of effective antimicrobials. The classical paradigm suggests that antibiotic resistance emerges by selection for pre-existing mutants in the bacterial population exposed to antibiotics. In contrast, recent data suggested that mutations evolve after cells encounter antibiotic therapy. This kind of mutation is known as adaptive mutation, which is activated by the SOS DNA repair and mutagenesis pathways. Accumulation of single-stranded DNA (ss-DNA) is the signal that induces the SOS response by promoting the formation of the RecA filament, which in turn activates the auto-cleavage activity of LexA and allows expression of SOS genes, including the SOS error-prone polymerases. In this project, phthalocyanine tetrasulfonic acid (PcTs)-based RecA inhibitors were characterized. PcTs molecules were found to potentiate the activity of bactericidal antibiotics and reduce the ability of bacteria to acquire antibiotic resistance mutations. This study highlights the ability of RecA inhibitors to potentiate the activity of antibiotics and provides a strategy for prolonging the life span of existing and newly developed antibiotics. We predicate that RecA inhibitors will be part of an antibiotic “cocktail” that enhances the activity of antibiotics and blocks resistance, which will ultimately prolong antibiotic lifespan.

No description available.

GABAergic interneurons in the basolateral complex (BLC) of the amygdala are a part of the emotional-learning circuitry of the brain and receive excitatory inputs from all sensory modalities via cortex and thalamus. Although the BLC, which is made up of the lateral amygdala (LA), basal amygdala (BA) and accessory basal nucleus, is under the influence of a strong inhibition brought about by local interneurons, little is known about the diversity, characteristics and functioning of these interneurons. In this study, I have characterised the BLC interneuron population using a transgenic mouse model in which enhanced green fluorescent protein has been tagged to the GAD67 promoter. This promoter is specifically expressed in all GABAergic interneurons, enabling us to visualise interneurons under UV light. Whole-cell recordings were made from GAD67 interneurons in the BLA to study their membrane and synaptic properties. On the basis of their firing properties, interneurons in the BLC were classified into six distinct groups. The calcium-binding proteins calbindin, calretinin and parvalbumin were found to be expressed differently in the LA and BA interneurons, with the majority of the interneurons in the LA expressing calretinin, whereas those in the BA mostly expressed parvalbumin. We also found diversity in the expression of postsynaptic glutamate receptors in the BLC. Long-term potentiation induced at the interneurons was specific to the cortical inputs in the LA. LTP was expressed only in interneurons that either lacked NMDA receptors or had NMDA receptors with fast decay kinetics. This form of LTP was mediated by calcium-permeable AMPA receptors and required a postsynaptic calcium rise for its induction This study shows that the interneurons in the BLC are a heterogenous population with respect to the expression of calcium-binding proteins, axonal morphology, synaptic and membrane properties. This heterogeneity in interneuron population may be essential for the specialised roles various types of interneurons play in the functioning of the amygdala and in emotional learning.

Complex training (CT; alternating between heavy and lighter load resistance exercises with similar movement patterns within an exercise session) is a form of training that may potentially bring about a state of postactivation potentiation, resulting in increased dynamic power (P max) and rate of force development during the lighter load exercise. Such a method may be more effective than either modality, independently for developing strength. The purpose of this research was to compare the effects of resistance training (RT), plyometric training (PT), and CT on lower body strength and anthropometrics. Thirty recreationally trained college-aged men were trained using 1 of 3 methods: resistance, plyometric, or complex twice weekly for 6 weeks. The participants were tested pre, mid, and post to assess back squat strength, Romanian dead lift (RDL) strength, standing calf raise (SCR) strength, quadriceps girth, triceps surae girth, body mass, and body fat percentage. Diet was not controlled during this study. Statistical measures revealed a significant increase for squat strength (p = 0.000), RDL strength (p = 0.000), and SCR strength (p = 0.000) for all groups pre to post, with no differences between groups. There was also a main effect for time for girth measures of the quadricepsmuscle group (p = 0.001), the triceps surae muscle group (p = 0.001), and body mass (p = 0.001; post hoc revealed no significant difference). There were main effects for time and group × time interactions for fat-free mass % (RT: p = 0.031; PT: p = 0.000). The results suggest that CT mirrors benefits seen with traditional RT or PT. Moreover, CT revealed no decrement in strength and anthropometric values and appears to be a viable training modality.

ABSTRACT: Wong, H, Gentles, J, Bazyler, C, and Ramsey, M. Exploring the utility of performing a down set as a postactivation potentiation strategy. J Strength Cond Res 35(5): 1217-1222, 2021-The purpose of this study was to determine if successive heavy sets of back squats can augment the concentric velocity of a lighter down set performed by strength-trained men. Twelve trained men with experience in the back squat volunteered to perform a 5 repetition maximum (5RM) along with 2 separate squat sessions consisting of 3 sets of 5 repetitions with 85% of their 5RM. One condition involved performing a "down set" (DS) after the 3 working sets at 85% of 5RM equivalent to 60% of the working-set load that was also performed during the warm-up. A "No down set" condition involved performing an additional warm-up set before the working sets with 60% of the working-set load instead of the down set to determine if velocity was augmented because of postactivation potentiation in the DS condition. In both conditions, 3 minutes of rest was applied between all sets. A paired sample t-test was used to compare the mean concentric velocities (MCVs) of the working sets of both conditions, and a repeated measures analysis of variance was used to assess differences in MCVs between sets performed at 60% of the working-set load. Cohen's d effect sizes were reported for all comparisons, and the critical alpha was set at p ≤ 0.05. No significant differences were observed in the working-set MCVs in both conditions (p = 0.412, d = 0.246) or between MCVs in the down set and equivalent warm-up set load in the DS condition (p = 0.270, d = 0.002).Although performing a down set may still be efficacious for developing power across a broad spectrum of loads, the results of this study suggest successive heavy sets of back squats do not acutely augment down set concentric velocity in strength-trained men.

Abstract Not Provided. / Thesis / Master of Science (MSc)