Reduced Inhibition within Layer IV of Sert Knockout Rat Barrel Cortex is Associated with Faster Sensory Integration.
Neural activity is essential for the maturation of sensory systems. In the rodent primary somatosensory cortex (S1), high extracellular serotonin (5-HT) levels during development impair neural transmission between the thalamus and cortical input layer IV (LIV). Rodent models of impaired 5-HT transporter (SERT) function show disruption in their topological organization of S1 and in the expression of activity-regulated genes essential for inhibitory cortical network formation. It remains unclear how such alterations affect the sensory information processing within cortical LIV. Using serotonin transporter knockout (Sert-/-) rats, we demonstrate that high extracellular serotonin levels are associated with impaired feedforward inhibition (FFI), fewer perisomatic inhibitory synapses, a depolarized GABA reversal potential and reduced expression of KCC2 transporters in juvenile animals. At the neural population level, reduced FFI increases the excitatory drive originating from LIV, facilitating evoked representations in the supragranular layers II/III. The behavioral consequence of these changes in network excitability is faster integration of the sensory information during whisker-based tactile navigation, as Sert-/- rats require fewer whisker contacts with tactile targets and perform object localization with faster reaction times. These results highlight the association of serotonergic homeostasis with formation and excitability of sensory cortical networks, and consequently with sensory perception.
Department of Cognitive Neuroscience, Radboudumc, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.|Department of Neural Networks, Center of Advanced European Studies and Research (caesar), Max Planck Society, Germany.
Stéphanie
S
Miceli
Department of Cognitive Neuroscience, Radboudumc, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.|Department of Human Genetics, Radboudumc, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
Nael
N
Nadif Kasri
Department of Cognitive Neuroscience, Radboudumc, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
Joep
J
Joosten
Department of Neurophysiology, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
Chao
C
Huang
Department of Cognitive Neuroscience, Radboudumc, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
Lara
L
Kepser
Department of Neurophysiology, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
Rémi
R
Proville
Department of Cognitive Neuroscience, Radboudumc, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
Martijn M
MM
Selten
Department of Cognitive Neuroscience, Radboudumc, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
Fenneke
F
van Eijs
Department of Neurophysiology, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
Alireza
A
Azarfar
Department of Cognitive Neuroscience, Radboudumc, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
Judith R
JR
Homberg
Department of Neurophysiology, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
Tansu
T
Celikel
Department of Cognitive Neuroscience, Radboudumc, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.|Department of Neurophysiology, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
Dirk
D
Schubert
D000818:Animals; D005110:Extracellular Space / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000473:pathology / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D055647:Rats, Transgenic; D017208:Rats, Wistar; D011930:Reaction Time / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2 / Q000378:metabolism; D013003:Somatosensory Cortex / Q000473:pathology / Q000502:physiology*; D065854:Spatial Navigation / Q000502:physiology*; D027981:Symporters / Q000378:metabolism; D046509:Tissue Culture Techniques; D055698:Touch Perception / Q000502:physiology*; D014738:Vibrissae / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000096922:K Cl- Cotransporters
D016601:RNA-Binding Proteins; D012701:Serotonin; D064506:Solute Carrier Family 12, Member 2; D027981:Symporters; D005680:gamma-Aminobutyric Acid; D000096922:K Cl- Cotransporters; C482440:Sert1 protein, rat; C578879:Slc12a2 protein, rat
5-HT; 5-HTT; feedforward inhibition; serotonin; somatosensory