Journal Article

DZNE-2026-00303

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Distinct roles of cortical layer 5 subtypes in associative learning.

Moberg, S. ; Garibbo, M. ; Mazo, C. ; Gilad, A. ; Schmitz, D.DZNE* ; Costa, R. P. ; Larkum, M. E. ; Takahashi, N.

2026
Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41467-026-68307-5

Abstract: Adaptive behavior relies on associating sensory cues with rewarding or aversive outcomes. In mammals, the primary sensory cortex processes stimuli and distributes information to cortical and subcortical targets. Layer 5 (L5) contains two major projection neuron classes, intratelencephalic (IT) and extratelencephalic (ET); however, their roles in associative learning remain unclear. Using transgenic mice, we identified IT and ET neurons in primary somatosensory cortex and tracked their activity with longitudinal two-photon imaging during Pavlovian conditioning with whisker stimulation. IT neurons stably encoded stimulus identity across training, whereas ET neurons showed dynamic changes that paralleled the emergence of anticipatory licking. Chemogenetic silencing of each subtype impaired learning in distinct, phase-specific ways. A reinforcement-learning model reproduced these dynamics, suggesting that IT neurons provide stable sensory representations needed to form cue-reward associations, while ET neurons encode reward expectation to refine behavior. These findings reveal complementary, cell-type-specific contributions of L5 neurons to associative learning.

Keyword(s): Animals (MeSH) ; Somatosensory Cortex: physiology (MeSH) ; Somatosensory Cortex: cytology (MeSH) ; Mice (MeSH) ; Mice, Transgenic (MeSH) ; Neurons: physiology (MeSH) ; Conditioning, Classical: physiology (MeSH) ; Association Learning: physiology (MeSH) ; Vibrissae: physiology (MeSH) ; Reward (MeSH) ; Male (MeSH) ; Mice, Inbred C57BL (MeSH) ; Cues (MeSH) ; Female (MeSH)

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Contributing Institute(s):

1. Network Dysfunction (AG Schmitz)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2026

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