WCU Publication

Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of hte perforant path

The after-effects of repetitive stimulation of the perforant path fibres to the dentate area of the hippocampal formation have been examined with extracellular micro-electrodes in rabbits anaesthetized with urethane.
In fifteen out of eighteen rabbits the population response recordedfrom granule cells in the dentate area to single perforant path volleys was potentiated for periods ranging from 30 min to 10 hr after one or more conditioning trains at 10-20/sec for 10-15 sec, or 100/sec for 3-4 sec.
The population response was analysed in terms of three parameters: the amplitude of the population excitatory post-synaptic potential (e.p.s.p.), signalling the depolarization of the granule cells, and the amplitude and latency of the population spike, signalling the discharge of the granule cells.
All three parameters were potentiated in 29% of the experiments; in other experiments in which long term changes occurred, potentiation was confined to one or two of the three parameters. A reduction in the latency of the population spike was the commonest sign of potentiation, occurring in 57 % of all experiments. The amplitude of the population e.p.s.p. was increased in 43 %, and of the population spike in 40 %, of all experiments.
During conditioning at 10-20/sec there was massive potentiation of the population spike ('frequency potentiation'). The spike was suppressed during stimulation at 100/sec. Both frequencies produced long-term potentiation.
The results suggest that two independent mechanisms are responsiblefor long-lasting potentiation: (a) an increase in the efficiency of synaptic transmission at the perforant path synapses; (b) an increase in the excitability of the granule cell population.

An Animal Model of a Behavioral Intervention for Depression

Although conditioned inhibition of fear (or learned safety) is a learning process critical for preventing chronic stress, a predisposing factor for depression and other psychopathologies, tittle is known about its functional purposes or molecular mechanisms. To obtain better insight into learned safety, we investigated its behavioral and molecular characteristics and found that it acts as a behavioral antidepressant in two animal models. Learned safety promotes the survival of newborn cells in the dentate gyrus of the hippocampus, while its antidepressant effect is abolished in mice with ablated hippocampal neurogenesis. Learned safety also increases the expression of BDNF in the hippocampus and leads to downregulation of genes involved in the dopaminergic and neuropeptidergic but not the serotonergic system in the basolateral amygdala. These data suggest that learned safety is an animal model of a behavioral antidepressant that shares some neuronal hallmarks of pharmacological antidepressants but is mediated by different molecular pathways.

Distinct Neural Bases of Route Following and Wayfinding in Humans An Animal Model of a Behavioral Intervention for Depression

Finding one's way in a large-scale environment may engage different cognitive processes than following a familiar route. The neural bases of these processes were investigated using functional MRI (fMRI). Subjects found their way in one virtual-reality town and followed a well-learned route in another. In a control condition, subjects followed a visible trail.Within subjects, accurate wayfinding activated the right posterior hippocampus. Between-subjects correlations with performance showed that good navigators (i.e., accurate wayfinders) activated the anterior hippocampus during wayfinding and head of caudate during route following. These results coincidewith neurophysiological evidence for distinct response (caudate) and place (hippocampal) representations supporting navigation. We argue that the type of representation used influences both performance and concomitant fMRI activation patterns.