Cofilin1 Controls Transcolumnar Plasticity in Dendritic Spines in Adult Barrel Cortex

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.

Sensory deprivation after focal ischemia in mice accelerates brain remapping and improves functional recovery through Arc-dependent synaptic plasticity

“…Similar to what is seen in perilesional cortex after ischemia, sensory deprivation results in increased spine turnover, implicating similar programs for structural and functional connectivity in deprived cortex (51). Arc is known to regulate dendritic spine dynamics through its interaction with actin-regulating proteins in dendritic spines (53)(54)(55). Thus, it is not surprising that post-ischemic spine density remains low in Arc-deficient mice.…”

Orofacial Neuropathic Pain Leads to a Hyporesponsive Barrel Cortex with Enhanced Structural Synaptic Plasticity

“…Indeed, ADF/Cofilin phosphorylation and dephosphorylation have been associated with spine growth and shrinkage during LTP and LTD, respectively [ 82 ]. Moreover, the number of p-Cofilin-positive puncta is dependent on excitatory transmission [ 83 , 84 ] and use of lentiviral vectors and optogenetically labelled cofilin1 knocked-down-neurons showed that cofilin-1 mediated actin dynamics regulates functional cortical map plasticity in an input-specific mechanism [ 85 ]. These data, combined with the upregulation of Piccolo and p-Cofilin observed in our model, suggest the presence of functional and structural plasticity induced by the neuropathic state in diverse cortical areas.…”

Off-Peak 594-nm Light Surpasses On-Peak 532-nm Light in Silencing Distant ArchT-Expressing Neurons In Vivo

“…We injected an adeno-associated virus vector encoding ArchT-GFP under the CaMKIIa promoter into the somatosensory area of rat cortex (Tsubota et al, 2015). Immunofluorescent double staining for GFP and a neuron-specific marker NeuN confirmed the selective expression with approximately 70% of ArchT-GFP in neurons (Figures 1C,D,and S1; see Transparent Methods ''Immunofluorescent analysis of ArchT-GFP expression in the rat cortex'' for details).…”

“…The pipette was left in place for 10 min before and 20 min after the injection. The scalp incision was carefully sutured, and the rat was returned to its home cage after recovering from anesthesia (Tsubota et al, 2015).…”