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:

Activity-dependent scaling of quantal amplitude in neocortical pyamidal neurons.Turrigiano, G.G., Leslie, K.R, Desai, N.S, Rutherford, L.C., and Nelson, S.B. (1998) Nature 391:892-895 (see also News and Views same issue) [abstract]

Opposite effects of BDNF on the quantal amplitude of pyramidal and interneuron excitatory synapses. Rutherford L.C., Nelson S.B., and Turrigiano, G.G. (1998) Neuron 21:521-530. [abstract]

Plasticity in the intrinsic excitability of neocortical pyramidal neurons. Desai, N.S., Rutherford, L.C., and Turrigiano, G.G. (1999). Nature Neuroscience 2:515-520 (see also News and Views same issue). [abstract]

Activity Co-regulated Quantal AMPA and NMDA Currents at Neocortical Synapses. Watt, A., van Rossum, M., MacLeod, K., Nelson, S.B., and Turrigiano, G.G. (2000) Neuron, 26:659-670 [abstract]

Stable Hebbian Learning from Spike-Timing Dependent Plasticity. Van Rossum, M.C., Bi, G., and Turrigiano, G.G. (2000) J. Neurosci. 20:8812-8821 [abstract]

Rate, timing, and cooperativity jointly determine cortical synaptic plasticity. Sjöström, P.J., Turrigiano, G.G. and Nelson, S.B. (2001) Neuron, 32:1149-1164 [abstract]

Activity Scales Inhibitory Synaptic strengths by Regulating the Number of Postsynaptic GABAa Receptors. Kilman, V, van Rossum, M.C., and Turrigiano, G.G. (2002) J. Neurosci, 22:1328-1337 [abstract]

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

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

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

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

Long-term Potentiation of Intrinsic Excitability in LV Visual Cortical Neurons. Cudmore RH, Turrigiano GG. (2004) J Neurophysiol. [abstract]

A proportional but slower NMDA potentiation follows AMPA potentiation in LTP. Watt AJ, Sjostrom PJ, Hausser M, Nelson SB, Turrigiano GG. (2004) Nat Neurosci. [abstract]

Endocannabinoid-dependent neocortical layer-5 LTD in the absence of postsynaptic spiking. Sjostrom PJ, Turrigiano GG, Nelson SB. (2004) J Neurophysiol. [abstract]

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

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

Temporal regulation of the expression locus of homeostatic plasticity. Wierenga CJ, Walsh MF, Turrigiano GG. (2006) J Neurophysiol. 2006 Oct;96(4):2127-33. Epub 2006 Jun 7. [abstract]

Potentiation of cortical inhibition by visual deprivation. Maffei A, Nataraj K, Nelson SB, Turrigiano GG. (2006) . Nature. 2006 Sep 7;443(7107):81-4. Epub 2006 Aug 23. [abstract]

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

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

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

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

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

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

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

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

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

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

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

Ten years of Nature Reviews Neuroscience: insights from the highly cited. 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. Nat Rev Neurosci. 2010 Oct;11(10):718-26. [abstract]

View Complete Publication List on PubMed: Gina Turrigiano

---

Last update: August 17, 2011.