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:

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

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

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

Varela, J.A., Song, S., Turrigiano, G.G., and Nelson, S.B. (1999) Differential depression at excitatory and inhibitory synapses in visual cortex. J. Neurosci. 19:4293-4304. [abstract]

Turrigiano, G.G. (1999) Homeostatic plasticity in neuronal networks: the more things change, the more they stay the same. Trends in Neuroscience 22:221-228. [abstract]

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

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

Turrigiano, G.G. (2000) AMPA receptors unbound: membrane cycling and synaptic plasticity. Neuron 26:5-8 [abstract]

Turrigiano, G.G. and Nelson, S.B. (2000) Hebb and Homeostasis in Neuronal Plasticity. Current Opinion in Neurobiology, 10:358-364. [abstract]

Leslie, K.R, Nelson, S.B., and Turrigiano, G.G. (2001) Postsynaptic Depolarization Scales Quantal Amplitude in Neocortical Pyramidal Neurons. J. Neurosci. 21: RC170 [abstract]

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

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

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

Turrigiano GG. (2002) A recipe for ridding synapses of the ubiquitous AMPA receptor. Trends Neurosci. 25:597-8. [abstract]

Nelson SB, Sjostrom PJ, Turrigiano GG. (2002) Rate and timing in cortical synaptic plasticity. Philos Trans R Soc Lond B Biol Sci. 357:1851-7. [abstract]

Myme CI, Sugino K, Turrigiano GG, Nelson SB. (2003) The NMDA-to-AMPA ratio at synapses onto layer 2/3 pyramidal neurons is conserved across prefrontal and visual cortices. J Neurophysiol. 90:771-9. [abstract]

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. [abstract]

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

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. [abstract]

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

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

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. [abstract]

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

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

Sjostrom PJ, Turrigiano GG, Nelson SB.(2006) Multiple forms of long-term plasticity at unitary neocortical layer 5 synapses. Neuropharmacology. 2006 Aug 6; [Epub ahead of print] [abstract]

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

 

View Complete Publication List on PubMed: Gina Turrigiano

 

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Last update: September 22, 2006.