Personnel
Regina Maldve - Research Associate
Paula Guerrero - Laboratory Technician
Selena Schreiber - Undergraduate Student
Lupe Reyna - Undergraduate Student
Morrisett Lab
Research Projects
My research focuses on the alterations in synaptic transmission that are thought to underlie the development of neuroadaptive responses which may contribute to the rewarding effects of ethanol and other drugs of addiction. The neural changes that promote alcohol abuse are thought to involve synaptic events within regions associated with the brainís reward circuitry such as the nucleus accumbens and the ventral tegmental area. Two neurotransmitters within this reward system, dopamine and glutamate, are important in the intoxication and addiction to alcohol.
One of our current projects involves a particular signaling pathway that we believe is associated with the initiating events of ethanol addiction. We have recently identified DARPP-32 (dopamine-and-c-AMP-regulated phosphoprotein, 32 kD) as a key neuroprotein in the modulation of the post-synaptic effects of ethanol on glutamatergic transmission. DARPP-32 is highly concentrated in the medium-spiny neurons of the neostriatum in close association with D1 dopamine receptors. Dopamine D1 receptor activation increases protein kinase A (PKA) activity and subsequent phosphorylation of DARPP-32 at threonine-34. Phospho-thr34-DARPP-32 potently inhibits protein phosphatase 1 thereby regulating numerous physiological substrates including an increase in NMDAR activity. NMDA receptor activation and induction of long-term potentiation are inhibited by ethanol, however the exact mechanisms remained elusive. However, in our recent publication in Nature Neuroscience, we proposed that the sensitivity of the NMDAR1 to ethanol may be regulated by the phosphorylation of DARPP-32.
Additionally, we are currently funded by the Texas Commission on Alcohol and Drug Abuse (TCADA) to examine ethanol effects on pre-synaptic function. Using FM1-43 fluorescence we can monitor the synaptic dynamics associated with ethanol treatment in situ. Individual synaptic boutons can be imaged real-time using confocal microscopy to monitor destaining associated with voltage-gated calcium channel (VGCC) depolarization.
The major techniques in our lab are SDS-page electrophoresis and immunofluorescence using an Olympus Fluoview FV-300 confocal microscope.
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