Presynaptic adenosine A1 receptors modulate excitatory transmission in the rat basolateral amygdala

Andrew R. Rau, Olusegun J. Ariwodola, Jeff L. Weiner

Research output: Contribution to journalArticlepeer-review

Abstract

The basolateral amygdala (BLA) plays an integral role in the etiology of anxiety disorders and alcoholism. Although much is known about the intrinsic circuitry that governs BLA excitability, our understanding of the neuromodulators that control BLA excitation is incomplete. In many brain regions, adenosine (ADO) regulates neuronal excitability, primarily via A 1 receptor inhibition of glutamate release, and basal adenosinergic tone is high enough to tonically inhibit neuronal excitation. Although ADO signaling modulates many anxiety- and alcohol-related behaviors, little is known about ADO regulation of BLA neurotransmission. To that end, we used patch clamp methods in rodent brain slices to characterize adenosinergic modulation of excitatory neurotransmission onto BLA pyramidal cells. ADO significantly inhibited EPSCs evoked by stimulation of either medial or external glutamatergic inputs into the BLA. This effect was mimicked by an A1, but not by an A2a, agonist. Paired-pulse ratio and miniature EPSC experiments revealed that A1 receptors reside at a presynaptic locus on BLA glutamatergic synapses. Moreover, bath application of an A1 receptor antagonist significantly enhanced EPSCs, providing evidence of tonic adenosinergic tone at BLA glutamatergic synapses. In addition, tonic ADO was regulated by adenosine kinase, but not adenosine deaminase. Finally, activation of A1 receptors had no direct effects on the intrinsic excitability of BLA pyramidal cells. Collectively, these data suggest that tonic A 1 receptor signaling may play an important role in regulating BLA excitability and suggest a possible neurobiological substrate through which ADO may contribute to the pathophysiology of anxiety disorders and alcohol addiction.

Original languageEnglish
Pages (from-to)465-474
Number of pages10
JournalNeuropharmacology
Volume77
DOIs
StatePublished - 2014

Keywords

  • Adenosine
  • Basolateral amygdala
  • Cyclopentyladenosine
  • EPSCs

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