title: Postsynaptic adenosine A2A receptors modulate intrinsic excitability of pyramidal cells in the rat basolateral amygdala.
abstract: BACKGROUND
  The basolateral amygdala plays a critical role in the etiology of anxiety disorders and addiction. Pyramidal neurons, the primary output cells of this region, display increased firing following exposure to stressors, and it is thought that this increase in excitability contributes to stress responsivity and the expression of anxiety-like behaviors. However, much remains unknown about the underlying mechanisms that regulate the intrinsic excitability of basolateral amygdala pyramidal neurons.
  
  
  METHODS
  Ex vivo gramicidin perforated patch recordings were conducted in current clamp mode where hyper- and depolarizing current steps were applied to basolateral amygdala pyramidal neurons to assess the effects of adenosine A(2A) receptor modulation on intrinsic excitability.
  
  
  RESULTS
  Activation of adenosine A(2A) receptors with the selective A(2A) receptor agonist CGS-21680 significantly increased the firing rate of basolateral amygdala pyramidal neurons in rat amygdala brain slices, likely via inhibition of the slow afterhyperpolarization potential. Both of these A(2A) receptor-mediated effects were blocked by preapplication of a selective A(2A) receptor antagonist (ZM-241385) or by intra-pipette infusion of a protein kinase A inhibitor, suggesting a postsynaptic locus of A(2A) receptors on basolateral amygdala pyramidal neurons. Interestingly, bath application of the A(2A) receptor antagonist alone significantly attenuated basolateral amygdala pyramidal cell firing, consistent with a role for tonic adenosine in the regulation of the intrinsic excitability of these neurons.
  
  
  CONCLUSIONS
  Collectively, these data suggest that adenosine, via activation of A(2A) receptors, may directly facilitate basolateral amygdala pyramidal cell output, providing a possible balance for the recently described inhibitory effects of adenosine A1 receptor activation on glutamatergic excitation of basolateral amygdala pyramidal cells.
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine (Mr Rau, Mr Ariwodola, and Dr Weiner), Neuroscience Graduate Program, Graduate School of Arts and Sciences (Mr Rau), Wake Forest University, Winston-Salem, North Carolina.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Rau
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine (Mr Rau, Mr Ariwodola, and Dr Weiner), Neuroscience Graduate Program, Graduate School of Arts and Sciences (Mr Rau), Wake Forest University, Winston-Salem, North Carolina.
authors.forename: Olusegun J
authors.initials: OJ
authors.lastname: Ariwodola
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine (Mr Rau, Mr Ariwodola, and Dr Weiner), Neuroscience Graduate Program, Graduate School of Arts and Sciences (Mr Rau), Wake Forest University, Winston-Salem, North Carolina. jweiner@wfubmc.edu.
authors.forename: Jeff L
authors.initials: JL
authors.lastname: Weiner
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D066272:Basolateral Nuclear Complex / Q000187:drug effects / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials; D066298:In Vitro Techniques; D008297:Male; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D020318:Rats, Long-Evans; D043705:Receptor, Adenosine A2A / Q000187:drug effects / Q000378:metabolism*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors
chemical_list: D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D047428:Protein Kinase Inhibitors; D043705:Receptor, Adenosine A2A; D017868:Cyclic AMP-Dependent Protein Kinases; D000241:Adenosine
keywords: A2A; AHP; adenosine; basolateral amygdala; intrinsic excitability