Synaptic alterations in the nucleus accumbens (NAc) are crucial for the aberrant reward-associated learning that forms the foundation of drug dependence. Glutamatergic synaptic plasticity in the NAc has been implicated in several behavioral responses to psychomotor stimulating agents, such as cocaine and amphetamine, yet no studies, at present, have investigated its modulation by ethanol. We demonstrated that both in vitro and in vivo ethanol treatment significantly disrupts normal synaptic functioning in medium spiny neurons (MSNs) of the NAc shell. Utilizing whole-cell voltage clamp recording techniques, synaptic conditioning (low frequency stimulation with concurrent postsynaptic depolarization) reliably depressed (NAc-LTD) AMPA-mediated excitatory postsynaptic currents (EPSCs). Acute ethanol exposure inhibited the depression of AMPA EPSCs differentially with increasing concentrations, but this inhibitory action of ethanol was reversed by a D1-like dopamine receptor agonist. When examined 24 hours following a single bout of in vivo chronic intermittent ethanol (CIE) vapor exposure, NAc-LTD was absent and instead synaptic potentiation (LTP) was reliably observed. We further investigated CIE-induced modulation of NAc-LTD by distinguishing between the two subpopulations of MSNs in the NAc, D1 receptor-expressing (D1+) and D2 receptor-expressing (D1-). We determined that NAc-LTD is expressed solely in D1+ but not D1- MSNs. In addition, 24 hours following a repeated regimen of in vivo CIE exposure NAc-LTD is completely occluded in D1+ MSNs, while D1- MSNs are able to express LTD. Complete recovery of normal synaptic plasticity expression in both D1+ and D1- MSNs does not occur until two weeks of withdrawal from CIE vapor exposure. To our knowledge, this is the first demonstration of a reversal in the cell type-specificity of synaptic plasticity in the NAc shell, as well as, the gradual recovery of the pre-drug exposure plasticity state following extended withdrawal. This study suggests that NAc-LTD is cell type-specific and highly sensitive to both acute and chronic ethanol exposure. We believe these observations also highlight the adaptability of NAc MSNs to the effects of long-term ethanol exposure. A change in these synaptic processes may constitute a neural adaptation that contributes to the induction and/or expression of alcohol dependence. / text

published_or_final_version / Mechanical Engineering / Doctoral / Doctor of Philosophy

One of the central questions of neuroscience research has been how the cellular and molecular components of the brain give rise to complex behaviours. Three major breakthroughs from the past sixty years have made the study of learning and memory central to our understanding of how the brain works. First, the psychologist Donald Hebb proposed that information storage in the brain could occur through the strengthening of the connections between neurons if the strengthening were restricted to neurons that were co-active (Hebb, 1949). Second, Milner and Scoville (1957) showed that the hippocampus is required for the acquisition of new long-term memories for consciously accessible, or declarative, information. Third, Bliss and Lømo (1973) demonstrated that the synapses between neurons in the dentate gyrus of the hippocampus could indeed be potentiated in an activity-dependent manner. Long-term potentiation (LTP) of the glutamatergic synapses in area CA1, the primary output of the hippocampus, has since become the leading model of synaptic plasticity due to its dependence on NMDA receptors (NMDARs), required for spatial and temporal learning in intact animals, and its robust pathway specificity. Using whole-cell recording in hippocampal slices from adult rats, I find that the efficacy of synaptic transmission from CA3 to CA1 can in fact be enhanced without the induction of classic LTP at the glutamatergic inputs. Taking care not to directly stimulate inhibitory fibers, I show that the induction of GABAergic plasticity at feedforward inhibitory inputs in CA1 results in the reduced shunting of excitatory currents, producing a long-term increase in the amplitude of Schaffer collateral-mediated postsynaptic potentials which is dependent on NMDAR activation and is pathway specific. The sharing of these fundamental properties with classic LTP suggests the possibility of a previously unrecognized target for therapeutic intervention in disorders linked to memory deficits, as well as a potentially overlooked site of LTP expression in other areas of the brain.

Prior work has shown that spinal neurons are capable of discriminating between temporally regular and temporally irregular stimulation. These effects have been observed using an in vivo assay of spinal plasticity based on an instrumental learning task, in which response-contingent leg shock produces an increase in flexion duration. Exposure to temporally regular stimulation (fixed spaced stimulation; FT) promotes learning, and temporally irregular stimulation produces a learning deficit. The experiments in this dissertation were designed to test other properties of fixed spaced shock that promote spinal plasticity and the structure responsible for the FT effect. Experiment 1 focused on the minimum number of stimulations necessary to re-establish the capacity to learn (a component of the “FT effect”), finding that180-360 shocks produced a learning deficit and that additional training (540-900 shocks) allowed learning. Experiment 2 found that shock number, not duration of exposure determined whether the FT effect emerged. Experiment 3 investigated if the FT effect emerges after shock was presented in two sessions separated by 24 hrs, and showed that two bouts of 360 shocks yielded the FT effect. Further, the initial bout of fixed spaced shock had a long-term benefit (Experiment 4). The results of Experiment 5 suggested that omitting shocks from a train of FT stimulation has little effect on the benefit of fixed spaced shock treatment. Experiment 6 replicated this observation, showing that randomly deleting half of the shocks (from a 720 FT shock series) had no effect on learning. Further, this schedule also induces a lasting protective effect, blocking the learning deficit produced by variable spaced shock (Experiment 7). To explore whether a central system or a peripheral filter mediates the FT effect, Experiment 8 challenged spinal neurons by phase shifting the relation between fixed spaced stimulation applied to two dermatomes. The FT effect only emerged when stimuli occurred in an alternating pattern across dermatomes, implying regularity is abstracted by a central system. Experiment 9 surgically isolated central pattern generator (L1-L2) from the portion of the spinal cord that mediates instrumental learning (L4-S2), finding that disrupting the connections between these two regions eliminated the FT effect.

The hybridizing Daphnia mendotae and D. dentifera (Crustacea: Cladocera) are sympatric throughout much of North America, and are considered a cryptic species complex due to their lack of phylogenetically informative morphological characters. They appear to have no biological mating barriers: hybrids may dominate or coexist with either or both parental species, and are sexually competent, forming both F2 hybrids and back-crosses. Nevertheless, the two species remain distinct. There is observational evidence that separation may be enforced by adaptation to different predation regimes: D. mendotae, with its greater anti-predator morphological plasticity, may out-compete D. dentifera under intense invertebrate predation, while the smaller D. dentifera may be better adapted to avoid predation by visually feeding fish. We tested this idea by examining whether D. mendotae and D. dentifera differ in ecologically relevant life history and morphological traits. We performed a replicated life history experiment involving 6 replicates of 6 clones within each species, and measured time until first reproduction, fecundity, and juvenile and population growth rates. In parallel, we examined whether these species differed in morphological traits predicted to arise from adaptation to different predator types, and tested the ecological relevance of these traits by exposing Daphnia to predation by the invasive cladoceran Bythotrephes longimanus. Finally, we examined the plasticity of life history, morphology, and susceptibility to predation by rearing Daphnia under exposure to Bythotrephes chemical cues for two generations. D. mendotae and D. dentifera differed across almost all measured life history and morphological traits in directions that accord with our hypotheses, strongly suggesting that their species boundaries are maintained by adaptation to different predation regimes. Plastic reaction to Bythotrephes, however, was weak and inconsistent, suggesting that these species either do not detect or respond to this recent invader, or that their responses are manifested in other ways. / Thesis (Master, Biology) -- Queen's University, 2011-12-23 20:31:14.76

No description available.

One of the central questions of neuroscience research has been how the cellular and molecular components of the brain give rise to complex behaviours. Three major breakthroughs from the past sixty years have made the study of learning and memory central to our understanding of how the brain works. First, the psychologist Donald Hebb proposed that information storage in the brain could occur through the strengthening of the connections between neurons if the strengthening were restricted to neurons that were co-active (Hebb, 1949). Second, Milner and Scoville (1957) showed that the hippocampus is required for the acquisition of new long-term memories for consciously accessible, or declarative, information. Third, Bliss and Lømo (1973) demonstrated that the synapses between neurons in the dentate gyrus of the hippocampus could indeed be potentiated in an activity-dependent manner. Long-term potentiation (LTP) of the glutamatergic synapses in area CA1, the primary output of the hippocampus, has since become the leading model of synaptic plasticity due to its dependence on NMDA receptors (NMDARs), required for spatial and temporal learning in intact animals, and its robust pathway specificity. Using whole-cell recording in hippocampal slices from adult rats, I find that the efficacy of synaptic transmission from CA3 to CA1 can in fact be enhanced without the induction of classic LTP at the glutamatergic inputs. Taking care not to directly stimulate inhibitory fibers, I show that the induction of GABAergic plasticity at feedforward inhibitory inputs in CA1 results in the reduced shunting of excitatory currents, producing a long-term increase in the amplitude of Schaffer collateral-mediated postsynaptic potentials which is dependent on NMDAR activation and is pathway specific. The sharing of these fundamental properties with classic LTP suggests the possibility of a previously unrecognized target for therapeutic intervention in disorders linked to memory deficits, as well as a potentially overlooked site of LTP expression in other areas of the brain.

No description available.

No description available.

No description available.