Date of Completion
Maxim Volgushev, John Salamone, Mary Bruno
Field of Study
Master of Science
Adenosine (ADO) is an abundant endogenous neuromodulator, with a generally suppressive effect on excitatory synaptic transmission. Previous research has shown that in different brain structures adenosine may have heterogeneous effects on the balance of N-methyl-D-aspartate (NMDA) receptor-mediated and non-NMDA receptor-mediated currents. In hippocampal pyramids, adenosine proportionally reduced the NMDA and non-NMDA mediated excitatory currents, whereas dopaminergic neurons in rat midbrain, adenosine preferentially reduced NMDA currents. It is known that in layer 2/3 pyramidal neurons of rat visual cortex, adenosine suppresses excitatory synaptic transmission. However, it remains unknown whether adenosine has the same effect on NMDA and AMPA-mediated currents. Here we asked whether NMDA-mediated currents are suppressed by adenosine differentially from AMPA-mediated currents, or whether the NMDA/AMPA balance is maintained in synaptic responses of layer 2/3 pyramids during application of adenosine. To test this, we conducted in vitro whole-cell recordings from layer 2/3 pyramids in slices from rat visual cortex and, studied synaptic currents evoked with stimulating electrodes located in layer 4. Mixed excitatory postsynaptic currents composed of AMPA and NMDA-mediated components were recorded on the background of blockade of inhibition by 2-100µM picrotoxin (PTX). Application of adenosine (20µM) led to a proportional decrease of NMDA and AMPA mediated currents, so that their balance in compound responses was maintained. These results were confirmed with recording of isolated NMDA and AMPA currents, which showed a similar reduction in amplitude. Thus, in synaptic inputs to layer 2/3 pyramidal neurons of rat visual cortex, adenosine reduces the amplitude of NMDA and AMPA-mediated currents proportionally.
Ellenberg, Justin T., "Proportional Suppression of NMDA and AMPA Mediated Synaptic Responses in Layer 2/3 Pyramids from Rat Visual Cortex by Adenosine" (2017). Master's Theses. 1090.