::: Current research in Stan Leung’s Laboratory :::

A general description of research is given in an interview in International Innovation

1. Generation and significance of neuronal oscillations in the hippocampus. Theta (4-10Hz) and gamma (30-100Hz) rhythms in the hippocampus are studied in behaving animals and in brain slices. Computational approach is used to elucidate the significance of extrinsic and intrinsic oscillations, which can explain theta-frequency spike precession in the place field. How theta phase shift within the hippocampus modulates synaptic transmission and plasticity is studied. 

2. Seizures and physiological and behavioral consequences. Various models of temporal lobe epilepsy (kindling, kainic acid, pilocarpine) and immature animal seizures (induced by hyperthermia or GABA-B receptor antagonist) are used. The physiological consequences of acute and chronic seizure activity are studied. Changes in neural circuits are studied in vivo using 16-channel electrodes, field potential recordings, and current source density analysis. Changes in synaptic properties are studied in vitro using intracellular and whole-cell recordings from brain slices. Behavioral consequences of experimental seizures are studied using a variety of cognitive (spatial maze) and motor (prepulse inhibition, behavioral activity) tasks. Our current emphasis is on psychiatric symptoms induced by animal models of temporal lobe epilepsy.

3. Long-term potentiation in the hippocampus and its cholinergic modulation. We showed the physiological release of endogenous acetylcholine, and its modulation by histamine, underlies the facilitation of long-term potentiation of the basal dendritic in the hippocampus of behaving rats.

4. Central mechanisms mediating general anesthesia. We reported that inactivation of the hippocampus, medial septum, nucleus accumbens, ventral pallidum and ventral tegmental area enhanced the potency of various anesthetics, suggesting the participation of the limbic system in mediating consciousness. Our studies on the participation of histaminergic tuberomammillary nucleus and nucleus basalis in general anesthesia, extend the concept that sleep and anesthesia share common mechanisms.

5. The septohippocampal system participates in schizophrenia. The symptoms induced by acute models of schizophrenia (induced by ketamine, MK-801) are partly mediated by the hippocampus, and alleviated by medial septal inactivation. The behavioral and electrophysiological assessments include sensorimotor gating (prepulse inhibition), auditory gating and locomotion.

6. Functional magnetic resonance imaging and EEG simultaneous recording during normal and seizure activity in animals are done in collaboration with Matt Hutchison, Seyed Mirsattari, Joe Gati and Ravi Menon. Recent studies showed a large number of independent components in the resting state BOLD signal in animals.