ABSTRACT
Layer 2/3 pyramidal cells (L2/3 PCs) play a crucial role in cortical information transfer. Although the dendritic arbors of L2/3 PCs are impressive, they often lack the distinct anatomical compartments characteristic of deeper L5 PCs. For example, many L2/3 PCs do not display an apparent distal tuft region. However, L2/3 PCs receive inputs from both thalamic (bottom-up) and cortical (top-down) inputs, which preferentially synapse onto their proximal and distal dendrites, respectively. Nonuniform organization of channels and NMDA receptors in L2/3 dendrites could serve to independently modulate these information streams to affect learning and behavior, yet whether L2/3 PC dendrites possess this capability has not been established. Here we found a previously unappreciated, non-uniform HCN channel distribution in L2/3 PCs, allowing for pathway-specific gating of NMDA receptor recruitment at bottom-up (proximal) but not top-down (distal) synapses. HCN availability shifted depending on developmental stage and neuromodulation, suggesting that the gain of thalamic and cortical-cortical signals in L2/3 may be independently modified in vivo across different timescales.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Revisions for this version were made in response to peer review at eLife (96002v1).