turrigianoGina Turrigiano, Ph.D.

Joseph Levitan Professor of Vision Science

Plasticity of the Synaptic and Intrinsic Properties of
Cortical Neurons and Circuits

Ph.D., University of California, San Diego

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Turrigiano Lab Home Page

During learning and development, the number and strength of synaptic inputs received by a neuron may change dramatically. While such changes are crucial in sculpting functional circuits and generating behavioral flexibility, they raise a compelling problem for the nervous system: that is, how do neurons and circuits maintain stability in their firing properties in the face of such dramatic synaptic reconfiguration? One possibility is that neuronal activity levels can homeostatically regulate the properties of neural circuits to maintain firing rates within certain boundaries. There are several possible targets for such activity-dependent regulation of firing rates. First, activity could modify intrinsic neuronal excitability by modifying the balance of conductances expressed by a neuron. Second, activity could globally scale synaptic strengths up or down. Third, activity could regulate the relative balance of excitation and inhibition received by a neuron. My lab is concerned with asking whether such homeostatic mechanisms operate in mammalian neocortical circuits, and determining how they interact to maintain both flexibility and stability in neural circuits function.

Measurement of miniature excitatory postsynaptic currents (mEPSCs)from cultured cortical pyramidal neurons grown under control conditions (Control), conditions of activity blockade (TTX), or conditions of activity enhancement (bicuculline). 48 hours of Activity blockade increases the amplitude of mEPSCs, whereas 48 hours of enhanced activity decreases mEPSC amplitude.

We use a combination of electrophysiological, biophysical, imaging, and computational techniques to address these issues. We have shown that activity can scale the strength of synaptic connections between pyramidal neurons in such a way as to maintain stability in firing rates; increased activity decreases synaptic strengths, and vice versa. Current research projects in our lab are designed to determine the mechanism of this synaptic scaling, to ask how different classes of synaptic connections are regulated by activity, and to ask whether synaptic scaling contributes to experience dependent plasticity of the visual system.

Selected Recent Publications:

Collingridge, G. L., D. Lodge, M. Mayer, G. Turrigiano and B. G. Frenguelli (2017). "Ionotropic glutamate receptors: Still exciting after all these years." Neuropharmacology 112(Pt A): 1-3.

Turrigiano, G. G. (2017). "The dialectic of Hebb and homeostasis." Philos Trans R Soc Lond B Biol Sci 372(1715).

Keck, T., T. Toyoizumi, L. Chen, B. Doiron, D. E. Feldman, K. Fox, W. Gerstner, P. G. Haydon, M. Hubener, H. K. Lee, J. E. Lisman, T. Rose, F. Sengpiel, D. Stellwagen, M. P. Stryker, G. G. Turrigiano and M. C. van Rossum (2017). "Integrating Hebbian and homeostatic plasticity: the current state of the field and future research directions." Philos Trans R Soc Lond B Biol Sci 372(1715).

Nahmani, M., C. Lanahan, D. DeRosier and G. G. Turrigiano (2017). "High-numerical-aperture cryogenic light microscopy for increased precision of superresolution reconstructions." Proc Natl Acad Sci U S A.

Steinmetz, C. C., V. Tatavarty, K. Sugino, Y. Shima, A. Joseph, H. Lin, M. Rutlin, M. Lambo, C. M. Hempel, B. W. Okaty, S. Paradis, S. B. Nelson and G. G. Turrigiano (2016). "Upregulation of mu3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway." Cell Rep 16(10): 2711-2722.

Hengen KB, Torrado Pacheco A, McGregor JN, Van Hooser SD and Turrigiano GG (2016). "Neuronal Firing Rate Homeostasis Is Inhibited by Sleep and Promoted by Wake." Cell 165(1): 180-191.

Adamantidis A, Arber S, Bains JS, Bamberg E, Bonci A, Buzsaki G, Cardin JA, Costa RM, Dan Y, Goda Y, Graybiel AM, Hausser M, Hegemann P, Huguenrd JR, Insel TR, Janak PH, Johnston D, Josselyn SA, Koch C, Kreitzer AC, Luscher C, Malenka RC, Miesenbock G, Nagel G, Roska B, Schnitzer MJ, Shenoy KV, Soltesz I, Sternson SM, Tsien RW, Tsien RY, Turrigiano GG, Tye KM and Wilson RI (2015). "Optogenetics: 10 years after ChR2 in neurons--views from the community." Nat Neurosci 18(9): 1202-1212.

Gainey MA, Tatavarty V, Nahmani M, Lin H and Turrigiano GG (2015). "Activity-dependent synaptic GRIP1 accumulation drives synaptic scaling up in response to action potential blockade." Proc Natl Acad Sci USA 112(27): E3590-3599.

Nahmani M and Turrigiano GG (2014). "Adult cortical plasticity following injury: Recapitulation of critical period mechanisms?" Neuroscience. 2014 Dec 26;283:4-16.

Nahmani M and Turrigiano GG (2014). "Deprivation-induced strengthening of presynaptic and postsynaptic inhibitory transmission in layer 4 of visual cortex during the critical period." J Neurosci. 2014 Feb 12;34(7):2571-82.

Taft CE and Turrigiano GG (2014). "PSD-95 promotes the stabilization of young synaptic contacts." Philos Trans R Soc Lond B Biol Sci. 2013 Dec 2;369(1633):20130134

Turrigiano G. (2014). "Neurobiology: Keeping a lid on it." Nature 511(7509): 297-298.

Hengen KB, Lambo ME, Van Hooser SD, Katz DB and Turrigiano GG (2013). "Firing rate homeostasis in visual cortex of freely behaving rodents." Neuron 80(2): 335-342.

Alivisatos AP, Andrews AM, Boyden ES, Chun M, Church GM, Deisseroth K, Donoghue JP, Fraser SE, Lippincott-Schwartz J, Looger LL, Masmanidis S, McEuen PL, Nurmikko AV, Park , Peterka DS, Reid C, Roukes ML, Scherer A, Schitzer M, Sejnowsk TJ, Shepard KL, Tsao D, Turrigiano G, Weiss PS, Xu C, Yuste R and Zhuang X (2013). "Nanotools for neuroscience and brain activity mapping." ACS Nano 7(3): 1850-1866.

Tatavarty V, Sun Q and Turrigiano GG (2013). "How to scale down postsynaptic strength." J Neurosci 33(32): 13179-13189.

Lambo ME and Turrigiano GG (2013). "Synaptic and intrinsic homeostatic mechanisms cooperate to increase L2/3 pyramidal neuron excitability during a late phase of critical period plasticity." J Neurosci33(20): 8810-8819.

Lefort S, Gray AC and Turrigiano GG (2013). "Long-term inhibitory plasticity in visual cortical layer 4 switches sign at the opening of the critical period." Proc Natl Acad Sci USA. 2013 Nov 19;110(47):E4540-7.

Loebrich S, Djukic B, Tong ZJ, Cottrell JR, Turrigiano GG and Nedivi E (2013). "Regulation of glutamate receptor internalization by the spine cytoskeleton is mediated by its PKA-dependent association with CPG2." Proc Natl Acad Sci USA 110(47): E4548-4556.

Blackman MP, Djukic B, Nelson SB and Turrigiano GG (2012). "A critical and cell-autonomous role for MeCP2 in synaptic scaling up." J Neurosci 32(39): 13529-13536.

Turrigiano G (2012). "Homeostatic synaptic plasticity: local and global mechanisms for stabilizing neuronal function." Cold Spring Harb Perspect Biol 4(1): a005736.

Nataraj K and Turrigiano GG (2011). "Regional and temporal specificity of intrinsic plasticity mechanisms in rodent primary visual cortex." J Neurosci 31(49): 17932-17940.

Sun Q and Turrigiano GG (2011). "PSD-95 and PSD-93 play critical but distinct roles in synaptic scaling up and down." J Neurosci 31(18): 6800-6808.

Turrigiano G (2011). "Too many cooks? Intrinsic and synaptic homeostatic mechanisms in cortical circuit refinement." Annu Rev Neurosci 34: 89-103.

Sun Q, Turrigiano GG (2011). "PSD-95 and PSD-93 play critical but distinct roles in synaptic scaling up and down." J Neurosci. 2011 May 4;31(18):6800-8.

Turrigiano G (2011). "Too many cooks? Intrinsic and synaptic homeostatic mechanisms in cortical circuit refinement." Annu Rev Neurosci. 2011;34:89-103.

Nataraj K, Le Roux N, Nahmani M, Lefort S, Turrigiano G (2010). "Visual deprivation suppresses L5 pyramidal neuron excitability by preventing the induction of intrinsic plasticity." Neuron. 2010 Nov 18;68(4):750-62.

Steinmetz CC, Turrigiano GG (2010). "Tumor necrosis factor-α signaling maintains the ability of cortical synapses to express synaptic scaling." J Neurosci. 2010 Nov 3;30(44):14685-90.

Luo L, Rodriguez E, Jerbi K, Lachaux JP, Martinerie J, Corbetta M, Shulman GL, Piomelli D, Turrigiano GG, Nelson SB, Joëls M, de Kloet ER, Holsboer F, Amodio DM, Frith CD, Block ML, Zecca L, Hong JS, Dantzer R, Kelley KW, Craig AD (2010). "Ten years of Nature Reviews Neuroscience: insights from the highly cited." Nat Rev Neurosci. 2010 Oct;11(10):718-26.

Maffei A, Lambo ME, Turrigiano GG (2010). "Critical period for inhibitory plasticity in rodent binocular V1." J Neurosci. 2010 Mar 3;30(9):3304-9

Gainey MA, Hurvitz-Wolff JR, Lambo ME, Turrigiano GG (2009). "Synaptic scaling requires the GluR2 subunit of the AMPA receptor." J Neurosci. 2009 May 20;29(20):6479-89.

Ibata K, Sun Q, Turrigiano GG (2008). "Rapid synaptic scaling induced by changes in postsynaptic firing." Neuron. 2008 Mar 27;57(6):819-26

Maffei A, Turrigiano GG (2008). "Multiple modes of network homeostasis in visual cortical layer 2/3." J Neurosci. 2008 Apr 23;28(17):4377-84.

Turrigiano GG (2008). "The self-tuning neuron: synaptic scaling of excitatory synapses." Cell. 2008 Oct 31;135(3):422-35.

Nelson SB, Turrigiano GG (2008). "Strength through diversity." Neuron. 2008 Nov 6;60(3):477-82.

Giorgi C, Yeo GW, Stone ME, Katz DB, Burge C, Turrigiano G, Moore MJ (2007). "The EJC factor eIF4AIII modulates synaptic strength and neuronal protein expression." Cell. 2007 Jul 13;130(1):179-91.

Wierenga CJ, Walsh MF, Turrigiano GG (2006). "Temporal regulation of the expression locus of homeostatic plasticity." J Neurophysiol. 2006 Oct;96(4):2127-33.

Maffei A, Nataraj K, Nelson SB, Turrigiano GG. (2006). "Potentiation of cortical inhibition by visual deprivation." Nature. 2006 Sep 7;443(7107):81-4.

Wierenga CJ, Ibata K, Turrigiano GG (2005). "Postsynaptic expression of homeostatic plasticity at neocortical synapses." J Neurosci. 2005 Mar 16;25(11):2895-905.

Maffei A, Nelson SB, Turrigiano GG. (2004). "Selective reconfiguration of layer 4 visual cortical circuitry by visual deprivation." Nat Neurosci. 2004 Dec;7(12):1353-9.

Turrigiano GG, Nelson SB (2004). "Homeostatic plasticity in the developing nervous system." Nat Rev Neurosci. 5:97-107.

Cudmore RH, Turrigiano GG. (2004). " Long-term Potentiation of Intrinsic Excitability in LV Visual Cortical Neurons." J Neurophysiol. 2004 Jul;92(1):341-8.

Watt AJ, Sjostrom PJ, Hausser M, Nelson SB, Turrigiano GG. (2004). "A proportional but slower NMDA potentiation follows AMPA potentiation in LTP." Nat Neurosci. 2004 May;7(5):518-24.

Sjostrom PJ, Turrigiano GG, Nelson SB. (2004). "Endocannabinoid-dependent neocortical layer-5 LTD in the absence of postsynaptic spiking." J Neurophysiol. 2004 Dec;92(6):3338-43.

Pratt KG, Watt AJ, Griffith LC, Nelson SB, Turrigiano GG (2003). "Activity-dependent remodeling of presynaptic inputs by postsynaptic expression of activated CaMKII." Neuron. 39:269-81.

Sjostrom PJ, Turrigiano GG, Nelson SB. (2003). "Neocortical LTD via coincident activation of presynaptic NMDA and cannabinoid receptors." Neuron. 39:641-54.

Kilman V, van Rossum MC and Turrigiano GG (2002). "Activity Scales Inhibitory Synaptic strengths by Regulating the Number of Postsynaptic GABAa Receptors." J. Neurosci, 22:1328-1337

Desai NS, Cudmore RH, Nelson SB and Turrigiano GG (2002). "Critical Periods for Experience-dependent synaptic scaling in visual cortex." Nature Neurosci. 5: 783-789

Sjöström PJ, Turrigiano GG and Nelson SB (2001) "Rate, timing, and cooperativity jointly determine cortical synaptic plasticity." Neuron, 32:1149-1164

Watt A, van Rossum M, MacLeod K, Nelson SB and Turrigiano GG (2000). "Activity Co-regulated Quantal AMPA and NMDA Currents at Neocortical Synapses." Neuron, 26:659-670

Van Rossum MC, Bi G, and Turrigiano GG (2000) "Stable Hebbian Learning from Spike-Timing Dependent Plasticity." J. Neurosci. 20:8812-8821

Desai NS, Rutherford LC and Turrigiano GG (1999). "Plasticity in the intrinsic excitability of neocortical pyramidal neurons." Nature Neuroscience 2:515-520 (see also News and Views same issue).

Turrigiano GG, Leslie KR, Desai NS, Rutherford LC and Nelson SB (1998). "Activity-dependent scaling of quantal amplitude in neocortical pyamidal neurons." Nature 391:892-895 (see also News and Views same issue)

Rutherford LC, Nelson SB and Turrigiano GG (1998) "Opposite effects of BDNF on the quantal amplitude of pyramidal and interneuron excitatory synapses." Neuron 21:521-530.

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Last update: April 3, 2017

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