Shifts in Developmental Timing, and Not Increased Levels of Experience-Dependent Neuronal Activity, Promote Barrel Expansion in the Primary Somatosensory Cortex of Rats Enucleated at Birth

Abstract

Birth-enucleated rodents display enlarged representations of whiskers (i.e., barrels of the posteromedial subfield) in the primary somatosensory cortex. Although the historical view maintains that barrel expansion is due to incremental increases in neuronal activity along the trigeminal pathway during postnatal development, recent evidence obtained in experimental models of intramodal plasticity challenges this view. Here, we re-evaluate the role of experience-dependent neuronal activity on barrel expansion in birth-enucleated rats by combining various anatomical methods and sensory deprivation paradigms. We show that barrels in birth-enucleated rats were already enlarged by the end of the first week of life and had levels of metabolic activity comparable to those in control rats at different ages. Dewhiskering after the postnatal period of barrel formation did not prevent barrel expansion in adult, birth-enucleated rats. Further, dark rearing and enucleation after barrel formation did not lead to expanded barrels in adult brains. Because incremental increases of somatosensory experience did not promote barrel expansion in birth-enucleated rats, we explored whether shifts of the developmental timing could better explain barrel expansion during the first week of life. Accordingly, birth-enucleated rats show earlier formation of barrels, accelerated growth of somatosensory thalamocortical afferents, and an earlier H4 deacetylation. Interestingly, when H4 deacetylation was prevented with a histone deacetylases inhibitor (valproic acid), barrel specification timing returned to normal and barrel expansion did not occur. Thus, we provide evidence supporting that shifts in developmental timing modulated through epigenetic mechanisms, and not increased levels of experience dependent neuronal activity, promote barrel expansion in the primary somatosensory cortex of rats enucleated at birth.

Prenatal thalamic waves regulate cortical area size prior to sensory processing

“…We found that the expansion of the PMBSF area and individual barrels in the adult embBE mouse is set during the first postnatal week, before the animal experiences any sensory input. These results are in line with recent observations in rodents enucleated at birth, where changes in gene expression and in the size of cortical areas were detected postnatally 23 44 . The fact that the enlargement of S1 and the reduction of A1 described in the MGv Kir mice are not correlated with a modification in the size of the respective thalamic nuclei supports a thalamo-cortical rather than a top-down 45 mechanism for plasticity.…”

“…Intriguingly, the plastic changes that occur in the cortex of sensory-deprived animals involve both the deprived and spared cortical areas. For example, removal of the eyes at birth leads to a reduction of the primary visual cortex and an expansion of the somatosensory cortical barrel-field in blind adult rodents 21 22 23 . Thus, there would appear to be some communication among distinct sensory systems and cortical areas, although the mechanisms that underlie such effects remain unexplored.…”

Permanent Whisker Removal Reduces the Density of c-Fos+ Cells and the Expression of Calbindin Protein, Disrupts Hippocampal Neurogenesis and Affects Spatial-Memory-Related Tasks

“…These tactile inputs are processed in the BC, at layer IV of the somatosensory cortex (Petersen, 2007 ). We produced a chronic tactile deprivation by fulgurating the vibrissal follicles as previously described (Fetter-Pruneda et al, 2013 ) and used the expression of cytochrome oxidase to label the BC (Wong-Riley and Welt, 1980 ). At day 30 after WD, the expression of cytochrome oxidase was not observed in the BC, indicating that tactile inputs were permanently disrupted by our method.…”

Visual system plasticity in mammals: the story of monocular enucleation-induced vision loss

“…These cross-modal alterations ultimately sharpen the tuning of barrel neurons in response to principal whisker stimulation (Jitsuki et al, 2011 ). Epigenetic changes, namely H4 deacetylation, are additional mechanisms that orchestrate the expansion of the barrel cortex following binocular enucleation in rats (Fetter-Pruneda et al, 2013 ). Together, these advances have led to subsequent whole cell recording experiments in juvenile mice with a different degree of visual deprivation (dark exposure, binocular enucleation and bilateral lid suturing) that confirmed distinct, independent functions and sensory requirements of unimodal vs. cross-modal synaptic plasticity.…”