Abstract
The generation of a synaptic current at the postsynaptic element (PSCs) is the result of a dynamic sequence of events including the release of the neurotransmitter, its diffusion in the synaptic cleft, and the activation of neurotransmitter receptors located at the postsynaptic side. It is widely accepted that the amplitude and the duration of PSCs are largely dictated by the gating properties of postsynaptic receptors. However, the knowledge of the properties of postsynaptic receptors is mostly derived from steady-state analysis, a condition that is substantially different from the non-equilibrium activation of synaptic receptors imposed by submillisecond neurotransmitter exposures. Given the technical limitations to reproduce the brief “synaptic-like” agonist pulse durations, the functioning of postsynaptic receptors during synaptic transmission is not fully elucidated and the “on-demand” postsynaptic activation of synapses cannot be easily achieved. In this chapter, we review the diverse approaches to study receptor gating at times relevant for synaptic transmission and novel optical/optogenetic techniques for controlling synaptic activity at the postsynaptic level. In addition, we emphasize the role of non-equilibrium in unmasking specific features of synaptic receptor gating and the recent advances in photonics for the light-control of neuronal activity at the single-receptor level.
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References
Branco T, Hausser M (2010) The single dendritic branch as a fundamental functional unit in the nervous system. Curr Opin Neurobiol 20(4):494–502. doi:10.1016/j.conb.2010.07.009
Klausberger T, Somogyi P (2008) Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations. Science 321(5885):53–57. doi:10.1126/science.1149381, 321/5885/53 [pii]
Tang CM, Margulis M, Shi QY, Fielding A (1994) Saturation of postsynaptic glutamate receptors after quantal release of transmitter. Neuron 13(6):1385–1393
Barberis A, Petrini EM, Cherubini E, Mozrzymas JW (2002) Allosteric interaction of zinc with recombinant alpha(1)beta(2)gamma(2) and alpha(1)beta(2) GABA(A) receptors. Neuropharmacology 43(4):607–618, S0028390802001090 [pii]
Bowie D, Lange GD (2002) Functional stoichiometry of glutamate receptor desensitization. J Neurosci 22(9):3392–3403, 20026333
Dravid SM, Prakash A, Traynelis SF (2008) Activation of recombinant NR1/NR2C NMDA receptors. J Physiol 586(Pt 18):4425–4439. doi:10.1113/jphysiol.2008.158634
Pitt SJ, Sivilotti LG, Beato M (2008) High intracellular chloride slows the decay of glycinergic currents. J Neurosci 28(45):11454–11467. doi:10.1523/JNEUROSCI.3890-08.2008
Barberis A, Petrini EM, Mozrzymas JW (2011) Impact of synaptic neurotransmitter concentration time course on the kinetics and pharmacological modulation of inhibitory synaptic currents. Front Cell Neurosci 5:6. doi:10.3389/fncel.2011.00006
Barberis A (2012) Fast perfusion methods for the study of ligand-gated ion channels. In: Fellin THM (ed) Neuronal network analysis, vol 67. Springer, New York, NY, pp 173–187. doi:10.1007/7657_2011_20
Jonas P (1995) Fast application of agonist to isolated membrane patches. In: Sakmann B, Neher E (eds) Single channel recordings. Plenum Press, New York, NY
De Angelis F, Das G, Candeloro P et al (2010) Nanoscale chemical mapping using three-dimensional adiabatic compression of surface plasmon polaritons. Nat Nanotechnol 5(1):67–72. doi:10.1038/nnano.2009.348
Franke C, Hatt H, Dudel J (1987) Liquid filament switch for ultra-fast exchanges of solutions at excised patches of synaptic membrane of crayfish muscle. Neurosci Lett 77(2):199–204
Moffatt L, Hume RI (2007) Responses of rat P2X2 receptors to ultrashort pulses of ATP provide insights into ATP binding and channel gating. J Gen Physiol 130(2):183–201. doi:10.1085/jgp.200709779
Clements JD, Lester RA, Tong G et al (1992) The time course of glutamate in the synaptic cleft. Science 258(5087):1498–1501
Mozrzymas JW, Barberis A, Michalak K, Cherubini E (1999) Chlorpromazine inhibits miniature GABAergic currents by reducing the binding and by increasing the unbinding rate of GABAA receptors. J Neurosci 19(7):2474–2488
He L, Wu XS, Mohan R, Wu LG (2006) Two modes of fusion pore opening revealed by cell-attached recordings at a synapse. Nature 444(7115):102–105. doi:10.1038/nature05250
Popescu G, Robert A, Howe JR, Auerbach A (2004) Reaction mechanism determines NMDA receptor response to repetitive stimulation. Nature 430(7001):790–793. doi:10.1038/nature02775
Barberis A, Petrini EM, Cherubini E (2004) Presynaptic source of quantal size variability at GABAergic synapses in rat hippocampal neurons in culture. Eur J Neurosci 20(7):1803–1810. doi:10.1111/j.1460-9568.2004.03624.x, EJN3624 [pii]
Min MY, Rusakov DA, Kullmann DM (1998) Activation of AMPA, kainate, and metabotropic receptors at hippocampal mossy fiber synapses: role of glutamate diffusion. Neuron 21(3):561–570, S0896-6273(00)80566-8 [pii]
Perrais D, Ropert N (2000) Altering the concentration of GABA in the synaptic cleft potentiates miniature IPSCs in rat occipital cortex. Eur J Neurosci 12(1):400–404, ejn957 [pii]
Barberis A, Sachidhanandam S, Mulle C (2008) GluR6/KA2 kainate receptors mediate slow-deactivating currents. J Neurosci 28(25):6402–6406. doi:10.1523/JNEUROSCI.1204-08.2008, 28/25/6402 [pii]
Jones MV, Westbrook GL (1995) Desensitized states prolong GABAA channel responses to brief agonist pulses. Neuron 15(1):181–191, 0896-6273(95)90075-6 [pii]
Petrini EM, Nieus T, Ravasenga T et al (2011) Influence of GABAAR monoliganded states on GABAergic responses. J Neurosci 31(5):1752–1761. doi:10.1523/JNEUROSCI.1453-10.2011
Mozrzymas JW, Barberis A, Mercik K, Zarnowska ED (2003) Binding sites, singly bound states, and conformation coupling shape GABA-evoked currents. J Neurophysiol 89(2):871–883. doi:10.1152/jn.00951.2002
Lester RA, Jahr CE (1992) NMDA channel behavior depends on agonist affinity. J Neurosci 12(2):635–643
Barberis A, Mozrzymas JW, Ortinski PI, Vicini S (2007) Desensitization and binding properties determine distinct alpha1beta2gamma2 and alpha3beta2gamma2 GABA(A) receptor-channel kinetic behavior. Eur J Neurosci 25(9):2726–2740. doi:10.1111/j.1460-9568.2007.05530.x, EJN5530 [pii]
Bragina L, Marchionni I, Omrani A et al (2008) GAT-1 regulates both tonic and phasic GABA(A) receptor-mediated inhibition in the cerebral cortex. J Neurochem 105(5):1781–1793. doi:10.1111/j.1471-4159.2008.05273.x
Macdonald RL, Rogers CJ, Twyman RE (1989) Kinetic properties of the GABAA receptor main conductance state of mouse spinal cord neurones in culture. J Physiol 410:479–499
Sachidhanandam S, Blanchet C, Jeantet Y et al (2009) Kainate receptors act as conditional amplifiers of spike transmission at hippocampal mossy fiber synapses. J Neurosci 29(15):5000–5008. doi:10.1523/JNEUROSCI.5807-08.2009
Mott DD, Rojas A, Fisher JL, Dingledine RJ, Benveniste M (2010) Subunit-specific desensitization of heteromeric kainate receptors. J Physiol 588(Pt 4):683–700, jphysiol.2009.185207 [pii]
Mozrzymas JW, Barberis A, Vicini S (2007) GABAergic currents in RT and VB thalamic nuclei follow kinetic pattern of alpha3- and alpha1-subunit-containing GABAA receptors. Eur J Neurosci 26(3):657–665. doi:10.1111/j.1460-9568.2007.05693.x, EJN5693 [pii]
Seeman P (1980) Brain dopamine receptors. Pharmacol Rev 32(3):229–313
Toone BK, Fenton GW (1977) Epileptic seizures induced by psychotropic drugs. Psychol Med 7(2):265–270
Mozrzymas JW, Zarnowska ED, Pytel M, Mercik K (2003) Modulation of GABA(A) receptors by hydrogen ions reveals synaptic GABA transient and a crucial role of the desensitization process. J Neurosci 23(22):7981–7992, 23/22/7981 [pii]
DiGregorio DA, Rothman JS, Nielsen TA, Silver RA (2007) Desensitization properties of AMPA receptors at the cerebellar mossy fiber granule cell synapse. J Neurosci 27(31):8344–8357. doi:10.1523/JNEUROSCI.2399-07.2007
Matsuzaki M, Ellis-Davies GC, Nemoto T et al (2001) Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons. Nat Neurosci 4(11):1086–1092. doi:10.1038/nn736
Trigo FF, Papageorgiou G, Corrie JE, Ogden D (2009) Laser photolysis of DPNI-GABA, a tool for investigating the properties and distribution of GABA receptors and for silencing neurons in situ. J Neurosci Methods 181(2):159–169. doi:10.1016/j.jneumeth.2009.04.022
Patneau DK, Mayer ML (1990) Structure-activity relationships for amino acid transmitter candidates acting at N-methyl-D-aspartate and quisqualate receptors. J Neurosci 10(7):2385–2399
Glykys J, Mody I (2007) Activation of GABAA receptors: views from outside the synaptic cleft. Neuron 56(5):763–770. doi:10.1016/j.neuron.2007.11.002
Levi S, Triller A (2006) Neurotransmitter dynamics. In: Kittler JT, Moss SJ (eds) The dynamic synapse: molecular methods in ionotropic receptor biology, Frontiers in neuroscience. CRC Press, Boca Raton, FL
Fino E, Araya R, Peterka DS et al (2009) RuBi-glutamate: two-photon and visible-light photoactivation of neurons and dendritic spines. Front Neural Circ 3:2. doi:10.3389/neuro.04.002.2009
Fino E, Yuste R (2011) Dense inhibitory connectivity in neocortex. Neuron 69(6):1188–1203. doi:10.1016/j.neuron.2011.02.025
Hayama T, Noguchi J, Watanabe S et al (2013) GABA promotes the competitive selection of dendritic spines by controlling local Ca2+ signaling. Nat Neurosci 16(10):1409–1416. doi:10.1038/nn.3496
Gorostiza P, Isacoff EY (2008) Optical switches for remote and noninvasive control of cell signaling. Science 322(5900):395–399. doi:10.1126/science.1166022
Szobota S, Gorostiza P, Del Bene F et al (2007) Remote control of neuronal activity with a light-gated glutamate receptor. Neuron 54(4):535–545. doi:10.1016/j.neuron.2007.05.010
Fenno L, Yizhar O, Deisseroth K (2011) The development and application of optogenetics. Annu Rev Neurosci 34:389–412. doi:10.1146/annurev-neuro-061010-113817
Bartels E, Wassermann NH, Erlanger BF (1971) Photochromic activators of the acetylcholine receptor. Proc Natl Acad Sci U S A 68(8):1820–1823
Banghart M, Borges K, Isacoff E et al (2004) Light-activated ion channels for remote control of neuronal firing. Nat Neurosci 7(12):1381–1386. doi:10.1038/nn1356
Chambers JJ, Banghart MR, Trauner D, Kramer RH (2006) Light-induced depolarization of neurons using a modified Shaker K(+) channel and a molecular photoswitch. J Neurophysiol 96(5):2792–2796. doi:10.1152/jn.00318.2006
Mathur BN, Tanahira C, Tamamaki N, Lovinger DM (2013) Voltage drives diverse endocannabinoid signals to mediate striatal microcircuit-specific plasticity. Nat Neurosci 16(9):1275–1283. doi:10.1038/nn.3478
Tye KM, Deisseroth K (2012) Optogenetic investigation of neural circuits underlying brain disease in animal models. Nat Rev Neurosci 13(4):251–266. doi:10.1038/nrn3171
Specht CG, Izeddin I, Rodriguez PC et al (2013) Quantitative nanoscopy of inhibitory synapses: counting gephyrin molecules and receptor binding sites. Neuron 79(2):308–321. doi:10.1016/j.neuron.2013.05.013
MacGillavry HD, Song Y, Raghavachari S, Blanpied TA (2013) Nanoscale scaffolding domains within the postsynaptic density concentrate synaptic AMPA receptors. Neuron 78(4):615–622. doi:10.1016/j.neuron.2013.03.009
Nair D, Hosy E, Petersen JD et al (2013) Super-resolution imaging reveals that AMPA receptors inside synapses are dynamically organized in nanodomains regulated by PSD95. J Neurosci 33(32):13204–13224. doi:10.1523/JNEUROSCI.2381-12.2013
Deshpande VV, Bockrath M, Glazman LI, Yacoby A (2010) Electron liquids and solids in one dimension. Nature 464(7286):209–216. doi:10.1038/nature08918
De Angelis F, Patrini M, Das G et al (2008) A hybrid plasmonic-photonic nanodevice for label-free detection of a few molecules. Nano Lett 8(8):2321–2327. doi:10.1021/nl801112e
Raether H (1988) Surface plasmons. Springer, Berlin
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This work was supported by the Telethon grant GGP11043 to A.B.
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Petrini, E.M., Barberis, A. (2014). Methods for the Study of Synaptic Receptor Functional Properties. In: Martina, M., Taverna, S. (eds) Patch-Clamp Methods and Protocols. Methods in Molecular Biology, vol 1183. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1096-0_7
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