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

Abstract

Facial vibrissae, commonly known as whiskers, are the main sensitive tactile system in rodents. Whisker stimulation triggers neuronal activity that promotes neural plasticity in the barrel cortex (BC) and helps create spatial maps in the adult hippocampus. Moreover, activity-dependent inputs and calcium homeostasis modulate adult neurogenesis. Therefore, the neuronal activity of the BC possibly regulates hippocampal functions and neurogenesis. To assess whether tactile information from facial whiskers may modulate hippocampal functions and neurogenesis, we permanently eliminated whiskers in CD1 male mice and analyzed the effects in cellular composition, molecular expression and memory processing in the adult hippocampus. Our data indicated that the permanent deprivation of whiskers reduced in 4-fold the density of c-Fos+ cells (a calcium-dependent immediate early gene) in cornu ammonis subfields (CA1, CA2 and CA3) and 4.5-fold the dentate gyrus (DG). A significant reduction in the expression of calcium-binding proteincalbindin-D28k was also observed in granule cells of the DG. Notably, these changes coincided with an increase in apoptosis and a decrease in the proliferation of neural precursor cells in the DG, which ultimately reduced the number of Bromodeoxyuridine (BrdU)+NeuN+ mature neurons generated after whisker elimination. These abnormalities in the hippocampus were associated with a significant impairment of spatial memory and navigation skills. This is the first evidence indicating that tactile inputs from vibrissal follicles strongly modify the expression of c-Fos and calbindin in the DG, disrupt different aspects of hippocampal neurogenesis, and support the notion that spatial memory and navigation skills strongly require tactile information in the hippocampus.

Tactile modulation of memory and anxiety requires dentate granule cells along the dorsoventral axis

“…An increase in DG neuronal activation by multimodal enrichment implies the potential link of DG to such circuits. Indeed, somatosensory deprivation or stimulation decreases or increases neuronal activity in S1 respectively 24 , 40 , while a similar bidirectional, tactile input-dependent activation of dDG neurons has been reported 23 , 24 . Similar to multimodal enrichment, unimodal tactile enrichment increased neuronal activation in the barrel field and trunk regions, which occupy ~70% of the S1 41 , and in the vDG.…”

“…The LEC is reciprocally connected with the S1 19 – 21 , and its layer 2 reelin-expressing neurons relay processed sensory information to the dentate gyrus (DG) 22 . Notably, dentate granule cell activity can be altered by tactile stimulation 23 or deprivation 24 . Since memory and anxiety are differentially modulated by DG neurons along the hippocampal dorsoventral axis 25 , 26 , it is possible that tactile inputs converge on the DG via the LEC to shape cognitive and emotional processes.…”

Cytosolic Ca2+Buffers Are Inherently Ca2+Signal Modulators

“…In the brain, CB-D28 expression is regulated by neuronal activity. Consistent whisker removal in mice, resulting in the inactivation of the main sensitive tactile system in rodents leads to CB-D28k down-regulation in hippocampal DG GCs paralleled by a loss of cells positive for the activity-driven (and Ca 2+ -dependent) immediate early gene c-Fos (Gonzalez-Perez et al 2018). The changes coincide with an increase in apoptosis and a decrease in the proliferation of neural DG precursor cells, further indicating that CB-D28k has an antiapoptotic function.…”

Hypoxia-Ischemia During a Neonatal Sensitive Period Alters Purkinje Neuron Dendritic Complexity Differently in Male and Female Rats

“…In addition, CALB and GFAP relative amounts were analyzed by measuring the integrated optical density (OD) as described in 71,72 . In brief, bright eld images were converted to grayscale, and the Image J Optical Density calibration tool was used to determine the intensity of CALB immunostaining in the PL and GFAP immunostaining in the GL and PL.…”