Sensory experience plays an important role in refining the connectivity of primary visual cortex, but the identity of the synaptic plasticity mechanisms that contribute to this refinement are still under debate. Most research has concentrated on the role of correlation-based plasticity mechanisms such as LTP and LTD, but these mechanisms are highly destabilizing and are unlikely to be sufficient to explain all of activity-dependent development. Using cultured cortical networks we identified a novel form of homeostatic synaptic plasticity that scales excitatory and inhibitory synaptic strengths up and down in the correct direction to stabilize the activity of cortical networks, and more recently we have demonstrated a similar phenomenon in vivo. Here we propose to examine the role of this homeostatic synaptic scaling in experience-dependent plasticity in vivo using a classic sensory deprivation paradigm, monocular deprivation (MD) and binocular deprivation (BD) using lid suture. MD and BD have been used extensively to study activity-dependent plasticity, but the effects of these manipulations on intracortical circuitry have never been probed in detail. We will approach this problem by manipulating activity in rodent visual cortex through MD and DR, then cutting slices of primary visual cortex and obtaining whole-cell recordings to measure quantal currents and paired synaptic transmission. We will ask whether the quantal currents for excitatory and inhibitory synapses are scaled in the opposite direction in response to altered visual input, whether this scaling displays critical periods as do other forms of activity-dependent plasticity, and whether the rules for synaptic scaling are specific for particular classes of excitatory and inhibitory inputs. These experiments will lay an important foundation for understanding the detailed changes in cortical circuitry that arise as a result of altered sensory experience, and will have important implications for the mechanisms of visual abnormalities such as amblyopia.

National Institute of Health (NIH)
National Eye Institute (NEI)
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Special Emphasis Panel (ZRG1-IFCN-4 (16))
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Oberdorfer, Michael
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Brandeis University
Schools of Arts and Sciences
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Turrigiano, Gina G (2017) The dialectic of Hebb and homeostasis. Philos Trans R Soc Lond B Biol Sci 372:
Hengen, Keith B; Torrado Pacheco, Alejandro; McGregor, James N et al. (2016) Neuronal Firing Rate Homeostasis Is Inhibited by Sleep and Promoted by Wake. Cell 165:180-191
Nahmani, Marc; Turrigiano, Gina G (2014) Deprivation-induced strengthening of presynaptic and postsynaptic inhibitory transmission in layer 4 of visual cortex during the critical period. J Neurosci 34:2571-82
Nahmani, M; Turrigiano, G G (2014) Adult cortical plasticity following injury: Recapitulation of critical period mechanisms? Neuroscience 283:4-16
Hengen, Keith B; Lambo, Mary E; Van Hooser, Stephen D et al. (2013) Firing rate homeostasis in visual cortex of freely behaving rodents. Neuron 80:335-42
Lefort, Sandrine; Gray, Annette C; Turrigiano, Gina G (2013) Long-term inhibitory plasticity in visual cortical layer 4 switches sign at the opening of the critical period. Proc Natl Acad Sci U S A 110:E4540-7
Nataraj, Kiran; Turrigiano, Gina (2011) Regional and temporal specificity of intrinsic plasticity mechanisms in rodent primary visual cortex. J Neurosci 31:17932-40
Turrigiano, Gina (2011) Too many cooks? Intrinsic and synaptic homeostatic mechanisms in cortical circuit refinement. Annu Rev Neurosci 34:89-103
Nataraj, Kiran; Le Roux, Nicolas; Nahmani, Marc et al. (2010) Visual deprivation suppresses L5 pyramidal neuron excitability by preventing the induction of intrinsic plasticity. Neuron 68:750-62
Maffei, Arianna; Lambo, Mary E; Turrigiano, Gina G (2010) Critical period for inhibitory plasticity in rodent binocular V1. J Neurosci 30:3304-9

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