The research in Dr. Kirkwood's lab elucidates the basic mechanisms by which visual experience can modify cortical connections in the visual cortex, and how those mechanisms are regulated.
Dr. Kirkwood and his team investigate two forms of activity-dependent synaptic plasticity in visual cortical slices: long-term potentiation (LTP) and long-term depression (LTD). These are currently the most comprehensive models of the elementary mechanisms underlying naturally occurring plasticity. Recent research has established that LTP and LTD have the appropriate properties to account for important features of naturally occurring synaptic modification in the visual cortex.
The lab is currently focused on how synaptic inhibition and the action of neuromodulators regulate the induction of LTP and LTD during development. The results of these investigations suggest two hypotheses: (1) the development of synaptic inhibition restricts the induction of LTP and LTD and, henceforth, the modification by experience to a short critical period, and (2) the action of neuromodulators released during arousal is to enhance the induction LTP and LTD by orders of magnitude, thus enabling experience to modify the visual cortex. By testing these specific hypotheses, they expect to gain a better understanding of how naturally occurring plasticity is regulated.
Ardiles AO, Ewer J, Acosta ML, Kirkwood A, Martinez AD, Ebensperger LA, Bozinovic F, Lee TM, Palacios AG. "Octodon degus (Molina 1782): a model in comparative biology and biomedicine." Cold Spring Harb Protoc. 2013 Apr 1;2013(4):312-8. doi: 10.1101/pdb.emo071357.
LeGates TA, Altimus CM, Wang H, Lee HK, Yang S, Zhao H, Kirkwood A, Weber ET, Hattar S. "Aberrant light directly impairs mood and learning through melanopsin-expressing neurons." Nature. 2012 Nov 22;491(7425):594-8. doi: 10.1038/nature11673. Epub 2012 Nov 14.
Guo Y, Huang S, de Pasquale R, McGehrin K, Lee HK, Zhao K, Kirkwood A. "Dark exposure extends the integration window for spike-timing-dependent plasticity." J Neurosci. 2012 Oct 24;32(43):15027-35. doi: 10.1523/JNEUROSCI.2545-12.2012.
Ardiles AO, Tapia-Rojas CC, Mandal M, Alexandre F, Kirkwood A, Inestrosa NC, Palacios AG. "Postsynaptic dysfunction is associated with spatial and object recognition memory loss in a natural model of Alzheimer's disease." Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13835-40. doi: 10.1073/pnas.1201209109. Epub 2012 Aug 6.
Huang S, Treviño M, He K, Ardiles A, Pasquale Rd, Guo Y, Palacios A, Huganir R, Kirkwood A. "Pull-push neuromodulation of LTP and LTD enables bidirectional experience-induced synaptic scaling in visual cortex." Neuron. 2012 Feb 9;73(3):497-510. doi: 10.1016/j.neuron.2011.11.023.