Coincidence detection in a neural correlate of classical conditioning is initiated by bidirectional 3‐phosphoinositide‐dependent kinase‐1 signalling and modulated by adenosine receptors

• Published in: The Journal of physiology 2015-04, Vol.593 (7), p.1581-1595
• Main Authors: Keifer, Joyce, Zheng, Zhaoqing
• Format: Article
• Language: English
• Subjects: 3-Phosphoinositide-Dependent Protein Kinases - physiology; Animals; Brain Stem - physiology; Conditioning, Classical - physiology; Cranial Nerves - physiology; Cyclic AMP-Dependent Protein Kinases - physiology; Neuroscience: Cellular/Molecular; Receptor, Adenosine A2A; Receptor, Nerve Growth Factor - physiology; Receptor, trkB - physiology; Turtles - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2014.282947

Key points Signalling mechanisms for coincidence detection of paired stimuli during classical conditioning are fundamental for understanding the mechanisms of associative learning. Bidirectional 3‐phosphoinositide‐dependent kinase‐1 (PDK1) activity is signalled by TrkB neurotrophin receptors for paired stimuli and p75NTR for unpaired stimuli. Adenosine 2A receptors modulate PDK1 responses directly as G proteins and by transactivation of TrkB. Convergence of protein kinase A and PDK1 activity initiates signalling of paired stimuli during classical conditioning. How the neural substrates for detection of paired stimuli are distinct from unpaired stimuli is poorly understood and a fundamental question for understanding the signalling mechanisms for coincidence detection during associative learning. To address this question, we used a neural correlate of eyeblink classical conditioning in an isolated brainstem from the turtle, in which the cranial nerves are directly stimulated in place of using a tone or airpuff. A bidirectional response is activated in