Bio

Bio


I am interested in studying learning and memory in epilepsy, and how optogenetic suppression of seizures can affect the cognitive deficits found in a mouse model of epilepsy.

Publications

All Publications


  • Dentate gyrus mossy cells control spontaneous convulsive seizures and spatial memory Science Bui, A., et al 2018: 787–90

    Abstract

    Temporal lobe epilepsy (TLE) is characterized by debilitating, recurring seizures and an increased risk for cognitive deficits. Mossy cells (MCs) are key neurons in the hippocampal excitatory circuit, and the partial loss of MCs is a major hallmark of TLE. We investigated how MCs contribute to spontaneous ictal activity and to spatial contextual memory in a mouse model of TLE with hippocampal sclerosis, using a combination of optogenetic, electrophysiological, and behavioral approaches. In chronically epileptic mice, real-time optogenetic modulation of MCs during spontaneous hippocampal seizures controlled the progression of activity from an electrographic to convulsive seizure. Decreased MC activity is sufficient to impede encoding of spatial context, recapitulating observed cognitive deficits in chronically epileptic mice.

    View details for DOI 10.1126/science.aan4074

  • Cannabinoid Control of Learning and Memory through HCN Channels NEURON Maroso, M., Szabo, G. G., Kim, H. K., Alexander, A., Bui, A. D., Lee, S., Lutz, B., Soltesz, I. 2016; 89 (5): 1059-1073

    Abstract

    The mechanisms underlying the effects of cannabinoids on cognitive processes are not understood. Here we show that cannabinoid type-1 receptors (CB1Rs) control hippocampal synaptic plasticity and spatial memory through the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels that underlie the h-current (Ih), a key regulator of dendritic excitability. The CB1R-HCN pathway, involving c-Jun-N-terminal kinases (JNKs), nitric oxide synthase, and intracellular cGMP, exerts a tonic enhancement of Ih selectively in pyramidal cells located in the superficial portion of the CA1 pyramidal cell layer, whereas it is absent from deep-layer cells. Activation of the CB1R-HCN pathway impairs dendritic integration of excitatory inputs, long-term potentiation (LTP), and spatial memory formation. Strikingly, pharmacological inhibition of Ih or genetic deletion of HCN1 abolishes CB1R-induced deficits in LTP and memory. These results demonstrate that the CB1R-Ih pathway in the hippocampus is obligatory for the action of cannabinoids on LTP and spatial memory formation.

    View details for DOI 10.1016/j.neuron.2016.01.023

    View details for PubMedID 26898775