Cofilin1 controls transcolumnar plasticity in dendritic spines in adult barrel cortex

PLoS Biol. 2015 Feb 27;13(2):e1002070. doi: 10.1371/journal.pbio.1002070. eCollection 2015 Feb.

Abstract

During sensory deprivation, the barrel cortex undergoes expansion of a functional column representing spared inputs (spared column), into the neighboring deprived columns (representing deprived inputs) which are in turn shrunk. As a result, the neurons in a deprived column simultaneously increase and decrease their responses to spared and deprived inputs, respectively. Previous studies revealed that dendritic spines are remodeled during this barrel map plasticity. Because cofilin1, a predominant regulator of actin filament turnover, governs both the expansion and shrinkage of the dendritic spine structure in vitro, it hypothetically regulates both responses in barrel map plasticity. However, this hypothesis remains untested. Using lentiviral vectors, we knocked down cofilin1 locally within layer 2/3 neurons in a deprived column. Cofilin1-knocked-down neurons were optogenetically labeled using channelrhodopsin-2, and electrophysiological recordings were targeted to these knocked-down neurons. We showed that cofilin1 knockdown impaired response increases to spared inputs but preserved response decreases to deprived inputs, indicating that cofilin1 dependency is dissociated in these two types of barrel map plasticity. To explore the structural basis of this dissociation, we then analyzed spine densities on deprived column dendritic branches, which were supposed to receive dense horizontal transcolumnar projections from the spared column. We found that spine number increased in a cofilin1-dependent manner selectively in the distal part of the supragranular layer, where most of the transcolumnar projections existed. Our findings suggest that cofilin1-mediated actin dynamics regulate functional map plasticity in an input-specific manner through the dendritic spine remodeling that occurs in the horizontal transcolumnar circuits. These new mechanistic insights into transcolumnar plasticity in adult rats may have a general significance for understanding reorganization of neocortical circuits that have more sophisticated columnar organization than the rodent neocortex, such as the primate neocortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry
  • Actins / genetics
  • Actins / metabolism
  • Action Potentials / physiology
  • Animals
  • Channelrhodopsins
  • Cofilin 1 / antagonists & inhibitors
  • Cofilin 1 / genetics*
  • Cofilin 1 / metabolism
  • Dendritic Spines / genetics
  • Dendritic Spines / metabolism*
  • Dendritic Spines / ultrastructure
  • Gene Expression
  • Gene Knockdown Techniques
  • Genetic Vectors
  • HEK293 Cells
  • Humans
  • Lentivirus / genetics
  • Lentivirus / metabolism
  • Male
  • Neocortex / metabolism*
  • Neocortex / ultrastructure
  • Neuronal Plasticity / physiology*
  • Optogenetics
  • PC12 Cells
  • Rats
  • Rats, Wistar
  • Sensory Deprivation / physiology
  • Somatosensory Cortex / metabolism*
  • Somatosensory Cortex / ultrastructure
  • Synapses / genetics
  • Synapses / metabolism*
  • Synapses / ultrastructure

Substances

  • Actins
  • Cfl1 protein, rat
  • Channelrhodopsins
  • Cofilin 1

Grants and funding

This work was supported by a grant from Core Research for Evolutional Science and Technology (CREST) program of the Japan Science and Technology Agency (KI, YM) (http://www.jst.go.jp/), a grant from Ministry of Education, Culture, Sports, Science, and Technology (MEXT) (http://www.mext.go.jp/) and JSPS (http://www.jsps.go.jp/) (grant number 23220009 to KI, 19002010 to YM, and 24220008 to YM), MEXT Grant-in-Aid Scientific Research on Innovative Areas (KI), a grant from Takeda Science Foundation (KI, YM) (http://www.takeda-sci.or.jp/), a Grant-in-Aid for Young Scientists from MEXT (grant number, 23700489; YO), Uehara Memorial Fund (YO) (http://www.ueharazaidan.or.jp/), and JSPS Research Fellowships for Young Scientists (grant number, 235569; TT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.