An increase in dendritic plateau potentials is associated with experience-dependent cortical map reorganization

Abstract

The organization of sensory maps in the cerebral cortex depends on experience, which drives homeostatic and long-term synaptic plasticity of cortico-cortical circuits. In the mouse primary somatosensory cortex (S1) afferents from the higher-order, posterior medial thalamic nucleus (POm) gate synaptic plasticity in layer (L) 2/3 pyramidal neurons via disinhibition and the production of dendritic plateau potentials. Here we address whether these thalamocortically mediated responses play a role in whisker map plasticity in S1. We find that trimming all but two whiskers causes a partial fusion of the representations of the two spared whiskers, concomitantly with an increase in the occurrence of POm-driven, N-methyl-D-aspartate receptor (NMDAR)-dependent plateau potentials. Blocking the plateau potentials restores the archetypical organization of the sensory map. Our results reveal a novel mechanism for experience-dependent cortical map plasticity in which higher-order thalamocortically mediated plateau potentials facilitate the fusion of normally segregated cortical representations.

Deficits in integrative NMDA receptors caused byGrin1disruption can be rescued in adulthood

“…Such temporal and spatial integration is required to generate dendritic plateau potentials 2,7,18,19 . These NMDAR-mediated integration events trigger burst firing 7,19 , a robust neuronal response 32,33 , thought to be essential for behaviour-evoked network activity 4,20,43 . Our results indicate that developmental disorders with reduced NMDARs are likely to have compromised neurophysiological integration resulting from disrupted extrasynaptic NMDAR population.…”

“…However, this view is shifting as growing preclinical research demonstrates the physiological conditions under which extrasynaptic NMDARs are recruited [15][16][17] . This recent body of work points to their role in normal brain function via generation of dendritic plateau potentials 3,4,42 . Extrasynaptic receptors bind the small amount of glutamate that escapes the synapse, to become 'primed' and ready for rapid activation by subsequent depolarizing input(s).…”

“…Such temporal and spatial integration is required to generate dendritic plateau potentials 2,7,18,19 . These NMDAR-mediated integration events trigger burst firing 7,19 , a robust neuronal response 32,33 , thought to be essential for behaviour-evoked network activity 4,20,43 and NMDAR radioligand binding 23 (to ~60% of wild-type), restores the neurophysiological phenomenon of dendritic plateau potentials. This integrative recovery is consistent with the marked improvement of cognitive performance observed after treatment in adulthood 23 .…”

“…Glutamatergic N-methyl-D-aspartate receptors (NMDARs) are increasingly appreciated for their role in cognitive integration [1][2][3][4] . Mutations that reduce expression or function of NMDARs are a direct cause of intellectual disability 5,6 .…”