Layer-specific cholinergic control of human and mouse cortical synaptic plasticity.
Individual cortical layers have distinct roles in information processing. All layers receive cholinergic inputs from the basal forebrain (BF), which is crucial for cognition. Acetylcholinergic receptors are differentially distributed across cortical layers, and recent evidence suggests that different populations of BF cholinergic neurons may target specific prefrontal cortical (PFC) layers, raising the question of whether cholinergic control of the PFC is layer dependent. Here we address this issue and reveal dendritic mechanisms by which endogenous cholinergic modulation of synaptic plasticity is opposite in superficial and deep layers of both mouse and human neocortex. Our results show that in different cortical layers, spike timing-dependent plasticity is oppositely regulated by the activation of nicotinic acetylcholine receptors (nAChRs) either located on dendrites of principal neurons or on GABAergic interneurons. Thus, layer-specific nAChR expression allows functional layer-specific control of cortical processing and plasticity by the BF cholinergic system, which is evolutionarily conserved from mice to humans.
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, De Boelelaan 1085, Amsterdam 1081 HV, The Netherlands.
Matthijs B
MB
Verhoog
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, De Boelelaan 1085, Amsterdam 1081 HV, The Netherlands.
Joshua
J
Obermayer
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, De Boelelaan 1085, Amsterdam 1081 HV, The Netherlands.
Christian A
CA
Kortleven
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, De Boelelaan 1085, Amsterdam 1081 HV, The Netherlands.
René
R
Wilbers
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, De Boelelaan 1085, Amsterdam 1081 HV, The Netherlands.
Jordi
J
Wester
Department of Neurosurgery, Neuroscience Campus Amsterdam, VU University Medical Center Amsterdam, De Boelelaan 1117, Amsterdam 1081 HV, The Netherlands.
Johannes C
JC
Baayen
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, De Boelelaan 1085, Amsterdam 1081 HV, The Netherlands.
Christiaan P J
CPJ
De Kock
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, De Boelelaan 1085, Amsterdam 1081 HV, The Netherlands.
Rhiannon M
RM
Meredith
Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, De Boelelaan 1085, Amsterdam 1081 HV, The Netherlands.
Huibert D
HD
Mansvelder
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D019579:Neocortex / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D011978:Receptors, Nicotinic / Q000502:physiology; D013569:Synapses
D011978:Receptors, Nicotinic; D009538:Nicotine; D000109:Acetylcholine