Proceedings of The Physiological Society

Physiology 2014 (London, UK) (2014) Proc Physiol Soc 31, PCB059

Poster Communications

Calcium-permeable AMPA receptors and synapse-specific plasticity in the neocortical layer-5 microcircuit

L. Txomin1,3, O. Julia2, R. P. Costa4, A. J. Chung1, M. Farrant2, J. Sjöström1,2

1. Centre for Research in Neuroscience, Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada. 2. Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom. 3. Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada. 4. Neuroinformatics Doctoral Training Centre, Institute for Adaptive and Neural Computation, School of Informatics, University of Edinburgh, Edinburgh, United Kingdom.

Short and long-term plasticity are synapse specific and depend on differences in synaptic molecular machinery (Blackman et al 2013; Lamsa et al, 2007). Little is known about the plasticity of inhibitory neurons, as they are difficult to classify (Ascoli et al, 2008).We examined plasticity at pyramidal cell (PC) synapses onto basket (BCs) and Martinotti cells (MCs) in layer 5 of visual cortex acute slices from postnatal day 12-21 mice. Animals were anaesthetized with isoflurane. MCs were targeted with GIN mice; other neurons with Dodt contrast in C57/BL6 mice. Neurons were identified by morphology, and spiking pattern when possible. With a 50-Hz induction protocol that consistently potentiated PC-PC synapses (after/before ± SEM = 120% ± 7%, n = 10, p < 0.05, Student's t-test), we observed non-Hebbian depression of both PC-BC (74% ± 7%, n = 7, p < 0.05) and PC-MC connections (54% ± 10%, n = 5, p < 0.05). In hippocampus, calcium-permeable (CP-) AMPARs underlie non-Hebbian plasticity (Lamsa et al, 2007). We thus investigated the presence of CP-AMPARs at these three synapse types. With intracellular loading of the polyamine spermine to specifically block CP-AMPARs at positive voltages (Cull-Candy et al, 2006), spontaneous currents in BCs showed inward rectification (rectification index RI+60mV/-60mV = 0.40 ± 0.03, n = 6, vs without spermine 1.32 ± 0.15, n = 4, p < 0.001). Evoked currents in PC-BC pairs also rectified (RI+40/-40 = 0.104 ± 0.04, p < 0.001, n = 6), suggesting the presence of CP-AMPARs. In agreement, the CP-AMPAR blocker NASPM reduced both spontaneous (61 ± 5%, n = 5, p < 0.01) and evoked currents in BCs (44% ± 4%, n = 5, p < 0.001). In contrast, PC-MC connections did not rectify with spermine (RI+40/-40 = 1.41 ± 0.15, p = 0.12, n = 4), suggesting the absence of CP-AMPARs. To study the postsynaptic side in isolation, we uncaged NPEC-AMPA with a 405-nm laser. Uncaging-evoked currents were reduced by NASPM in BCs (61% ± 5%, n = 7, p < 0.001) but not MCs or PCs (99% ± 10%, n = 4, p = 0.96). In addition, uncaging-evoked currents rectified in BCs (RI+40/-40 = 0.10 ± 0.09, p < 0.001, n = 8) but not in MCs (RI+40/-40 = 0.97 ± 0.1, p = 0.8, n = 6). Finally, preliminary simulations using a computer network model tuned to our short-term plasticity data suggested that CP-AMPARs impact fast BC but not slow MC feedback inhibition onto PCs.In conclusion, CP-AMPARs are specifically expressed at PC-BC but not PC-MC connections, yet both connection types show non-Hebbian plasticity, which means CP-AMPARs do not alone determine non-Hebbian plasticity. However, synapse-specific CP-AMPAR expression may govern early BC and late MC feedback inhibition. Such synapse-specific plasticity may critically influence information processing in local networks (Blackman et al, 2013).

Where applicable, experiments conform with Society ethical requirements