It has long been appreciated that visual experience during an early critical period is essential for the normal maturation of visual cortex. Studies on animals reared in different environments have established that during this critical period, visual cortical connections can be modified in an activity dependent manner. Those studies have also shown that visual cortical plasticity depends on neuromodulary systems and on the strength of intracortical inhibition. The long-term goal of this project is to elucidate the cellular mechanisms by which age, neuromodulators and synaptic inhibition control synaptic modification in visual cortex. This proposal focuses on the regulation of two forms of synaptic modification that are believed to be involved in natural occurring plasticity: long-term potentiation (LTP) and long-term depression (LTD). The studies are aimed to test two hypotheses concerning how neuromodulators and synaptic inhibition might regulate the induction of these forms of plasticity. The first hypothesis states that specific neuromodulators are essential to selectively gate or prime the induction of LTP and LTD. The second hypothesis states that developmental increases in the strength of synaptic inhibition reduces or prevents the induction of LTP and LTD. The experiments will be performed in slices made from the visual cortex of rats and mice of different ages and raised in different environments. Changes in LTP and LTD will be compared with reported changes in naturally-occurring synaptic modifications. Understanding how LTP and LTD are regulated will yield insights into the mechanisms underlying the critical period and will provide a cellular understanding of the integrative aspects of cortical plasticity. Besides the obvious relevance of this neural plasticity to the development of visual capabilities, it seems likely that similar processes may form the basis for some forms of learning and memory in the adult brain.
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| Kirkwood, Alfredo (2015) Balancing excitation and inhibition. Neuron 86:348-50 |
| He, Kaiwen; Huertas, Marco; Hong, Su Z et al. (2015) Distinct Eligibility Traces for LTP and LTD in Cortical Synapses. Neuron 88:528-38 |
| Huang, Shiyong; Hokenson, Kristen; Bandyopadhyay, Sabita et al. (2015) Brief Dark Exposure Reduces Tonic Inhibition in Visual Cortex. J Neurosci 35:15916-20 |
| Huang, Shiyong; Rozas, Carlos; Treviño, Mario et al. (2014) Associative Hebbian synaptic plasticity in primate visual cortex. J Neurosci 34:7575-9 |
| Yang, Sungchil; Yang, Sunggu; Park, Jae-Sung et al. (2014) Failed stabilization for long-term potentiation in the auditory cortex of FMR1 knockout mice. PLoS One 9:e104691 |
| Huang, Shiyong; Huganir, Richard L; Kirkwood, Alfredo (2013) Adrenergic gating of Hebbian spike-timing-dependent plasticity in cortical interneurons. J Neurosci 33:13171-8 |
| Gu, Yu; Huang, Shiyong; Chang, Michael C et al. (2013) Obligatory role for the immediate early gene NARP in critical period plasticity. Neuron 79:335-46 |
| Guo, Yatu; Huang, Shiyong; de Pasquale, Roberto et al. (2012) Dark exposure extends the integration window for spike-timing-dependent plasticity. J Neurosci 32:15027-35 |
| Huang, ShiYong; Treviño, Mario; He, Kaiwen et al. (2012) Pull-push neuromodulation of LTP and LTD enables bidirectional experience-induced synaptic scaling in visual cortex. Neuron 73:497-510 |
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