 |
| 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. |
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.
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 GG. The self-tuning neuron: synaptic scaling of excitatory synapses. Cell. 2008;135(3):422-35.
Pratt KG, Taft CE, Burbea M, Turrigiano GG. Dynamics underlying synaptic gain between pairs of cortical pyramidal neurons. Dev Neurobiol. 2008;68(2):143-51.
Nelson SB, Turrigiano GG. Strength through diversity. Neuron. 2008;60(3):477-82.
Maffei A, Turrigiano GG. Multiple modes of network homeostasis in visual cortical layer 2/3. J Neurosci. 2008;28(17):4377-84.
Maffei A, Turrigiano G. Chapter 12 The age of plasticity: Developmental regulation of synaptic plasticity in neocortical microcircuits. Prog Brain Res. 2008;169:211-23.
Ibata K, Sun Q, Turrigiano GG. Rapid synaptic scaling induced by changes in postsynaptic firing. Neuron. 2008;57(6):819-26.
Turrigiano G. Homeostatic signaling: the positive side of negative feedback. Current Opinion in Neurobiology. 2007;17(3):318-24.
Sjostrom PJ, Turrigiano GG, Nelson SB. Multiple forms of long-term plasticity at unitary neocortical layer 5 synapses. Neuropharmacology. 2007;52(1):176-84.
Giorgi C, Yeo GW, Stone ME, Katz DB, Burge C, Turrigiano G, et al. The EJC factor eIF4AIII modulates synaptic strength and neuronal protein expression. Cell. 2007;130(1):179-91.
Wierenga CJ, Walsh MF, Turrigiano GG. Temporal regulation of the expression locus of homeostatic plasticity. J Neurophysiol. 2006;96(4):2127-33.
Turrigiano GG. More than a sidekick: glia and homeostatic synaptic plasticity. Trends Mol Med. 2006;12(10):458-60.
Turrigiano G. Maintaining your youthful spontaneity: microcircuit homeostasis in the embryonic spinal cord. Neuron. 2006;49(4):481-3.
Sjostrom PJ, Turrigiano GG, Nelson SB. Multiple forms of long-term plasticity at unitary neocortical layer 5 synapses. Neuropharmacology. 2006.
Maffei A, Nataraj K, Nelson SB, Turrigiano GG. Potentiation of cortical inhibition by visual deprivation. Nature. 2006;443(7107):81-4.
Wierenga CJ, Ibata K, Turrigiano GG. Postsynaptic expression of homeostatic plasticity at neocortical synapses. J Neurosci. 2005;25(11):2895-905.
Dani VS, Chang Q, Maffei A, Turrigiano GG, Jaenisch R, Nelson SB. Reduced cortical activity due to a shift in the balance between excitation and inhibition in a mouse model of Rett Syndrome. Proc Natl Acad Sci U S A. 2005;102(35):12560-5.
View Complete Publication List on PubMed:
Gina Turrigiano
Last update: Feb 5, 2009. E-mail comments
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