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.

Alterations in both structural and synaptic plasticity in the adult brain have been implicated in impaired learning and memory. In the present study, we investigated if hippocampal plasticity is affected in the transgenic YAC128 mouse model of Huntington disease (HD). Reductions in adult hippocampal neurogenesis were observed in the dentate gyrus (DG) of early symptomatic to end-stage mice compared with wild-type (WT) controls, however there were no changes in cell proliferation and differentiation in the subventricular zone. Early symptomatic mice also displayed attenuated paired-pulse plasticity and long-term depression in the DG, while long-term potentiation was found to be normal in YAC128 mice. The changes in hippocampal plasticity may contribute to the cognitive abnormalities observed in these animals. / Graduate / 0306

This thesis examined the effects of temporary inactivation of the dorsal or ventral hippocampus on unconditioned and conditioned fear, using the shock-probe test. Rats received either dorsal or ventral hippocampal infusions of Lidocaine, muscimol or saline, before or after exposure to an electrified shock-probe. A retention test in the same apparatus was given 24 hr later, at which time the hippocampus was no longer inactivated, and the probe was disconnected from the shock-source. We found that ventral hippocampal inactivation impaired fear behaviour during acquisition, and dorsal hippocampal inactivation impaired fear behaviour during retention. We conclude that the: 1) ventral hippocampus mediates unconditioned fear behaviour, 2) the dorsal hippocampus mediates fear memory and 3) afferent input from brain structures located outside of the hippocampus are not responsible for the differential effects of dorsal and ventral hippocampal inactivation on fear and memory. / Behaviour, Systems and Cognitive Neuroscience

Proefschr. Rijksuniversiteit Groningen. / Met bibliogr., lit.opg.-Met samenvatting in het Nederlands.

Proefschrift Universiteit van Amsterdam. / Met lit. opg., bibliogr. - Met samenvatting in het Nederlands.

Proefschrift Universiteit van Amsterdam. / Auteursnaam op omslag: Corette Wierenga. Met lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Universiteit van Amsterdam. / Auteursnaam op omslag: Aren Borgdorff. Met lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Universiteit van Amsterdam. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.