Adenosine A1 receptor activation mediates the developmental shift at layer 5 pyramidal cell synapses and is a determinant of mature synaptic strength

• Published in: The Journal of physiology 2013-07, Vol.591 (13), p.3371-3380
• Main Authors: Kerr, Michael I., Wall, Mark J., Richardson, Magnus J. E.
• Format: Article
• Language: English
• Subjects: Adenosine; Adenosine - physiology; Aging - physiology; Animals; In Vitro Techniques; Male; Models, Biological; Neocortex - physiology; Neuronal Plasticity; Neuroscience: Development/Plasticity/Repair; Pyramidal Cells - physiology; Rats; Rats, Wistar; Receptor, Adenosine A1 - physiology; Rodents; Somatosensory Cortex - physiology; Synapses - physiology; Synaptic Transmission
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2012.244392

Key points •  Neocortical layer 5 pyramidal cell synapses exhibit a developmental reduction in neurotransmitter release probability. Mature synapses are weaker, less reliable and show greater facilitation than immature connections. •  Using paired intracellular recordings our study identifies the mechanism that mediates this developmental change as being due to an increased activation of presynaptic adenosine A1 receptors. •  Unlike immature connections, which showed little A1 receptor activation, mature connections demonstrated a broad range of activation that was inversely correlated to mature synaptic strength. •  We show that the functional efficacy of A1 receptors does not change over development and so our evidence points to concentrations of extracellular adenosine at synapses increasing locally over development. •  The increased adenosine levels significantly affect synaptic efficacy suggesting that the emplacement of adenosine sources and sinks might be a novel mechanism for long‐term plasticity at layer 5 pyramidal cell synapses.   During the first postnatal month glutamatergic synapses between layer 5 pyramidal cells in the rodent neocortex switch from an immature state exhibiting a high probability of neurotransmitter release, large unitary amplitude and synaptic depression to a mature state with decreased probability of release, smaller unitary amplitude and synaptic facilitation. Using paired recordings, we demonstrate that the developmental shift in release probability at synapses between rat somatosensory layer 5 thick‐tufted pyramidal cells is mediated by a higher and more heterogeneous activation of presynaptic adenosine A1 receptors. Immature synapses under control conditions exhibited distributions of coefficient of variation, failure rate and release probability that were almost coincident with the A1 receptor blocked condition; however, mature synapses under control conditions exhibited much broader distributions that spanned those of both the A1 receptor agonized and antagonized conditions. Immature and mature synapses expressed A1 receptors with no observable difference in functional efficacy and therefore the heterogeneous A1 receptor activation seen in the mature neocortex appears due to increased adenosine concentrations that vary between synapses. Given the central role demonstrated for A1 receptor activation in determining synaptic amplitude and the statistics of transmission between mature layer 5 pyramidal cells, the emplacem