Уважаемые коллеги, 5 августа 2014 года (вторник) в 16:00 состоится семинар проф. А. С. Кузнецова, Университет Индианы (Индианаполис, США) на тему: "Dopamine signaling: recent advances and open questions". Семинар состоится в конференц-зале (3 этаж) в НИИ ИЖС (7 корпус).
Dopamine is a neurotransmitter that has been found to play a role in the motivation of animal and human behavior and psychiatric disorders. The release of dopamine is regulated by the firing patterns of midbrain dopaminergic (DA) neurons. The neurons display two distinct patterns of spiking: low frequency tonic spiking and burst-like episodes of short high-frequency spiking. In vivo, the high-frequency episodes are irregular events that can be observed upon exposure to unpredicted stimuli perceived as rewarding. How the stimuli evoke the bursts is not clear. In order to explore the mechanisms of bursting, we created a model that reproduces the major excitability properties of the DA neuron. First, the high frequency firing cannot be triggered by tonic applied depolarization, which evokes a blockade of oscillations instead. Second, two apparently similar inputs, tonic NMDA and AMPA receptor activation elicit distinct responses – a high frequency for the former, and a block for the latter. We reduce the model to 3-dimentional system of ODEs with a separation onto one fast and two slow variables. The system allows for further mathematical analysis of different firing patterns that should correspond to distinct DA release. Additionally, we build the DA release and reuptake subsystem and calibrate it according to experimental data on the blockade of the DA transporter by cocaine. Furthermore, we build local circuitry that include DA neurons and show how an inhibitory drive can promote bursting, and, thus, elevated DA release. The model explains recent experimental data on nicotine modulation of DA neuron firing and DA release.