TY - JOUR
T1 - Anterolateral motor cortex connects with a medial subdivision of ventromedial thalamus through cell type-specific circuits, forming an excitatory thalamo-cortico-thalamic loop via layer 1 apical tuft dendrites of layer 5B pyramidal tract type neurons
AU - Guo, Kuanghua
AU - Yamawaki, Naoki
AU - Svoboda, Karel
AU - Shepherd, Gordon M.G.
N1 - Funding Information:
This research was supported by National Institutes of Health Grants T32-MH-067564 (K.G.) and R01-NS-061963 (G.M.G.S.). We thank N. Bernstein and C. Maguire for technical assistance. We also thank L. Acsády for discussions and suggestions, and J. Barrett and H. Inagaki for comments on the manuscript. Correspondence should be addressed to Gordon M.G. Shepherd, Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611. E-mail: g-shepherd@northwestern.edu. DOI:10.1523/JNEUROSCI.1333-18.2018 Copyright © 2018 the authors 0270-6474/18/388787-11$15.00/0
PY - 2018/10/10
Y1 - 2018/10/10
N2 - The anterolateral motor cortex (ALM) and ventral medial (VM) thalamus are functionally linked to support persistent activity during motor planning. We analyzed the underlying synaptic interconnections using optogenetics and electrophysiology in mice (female/male). In cortex, thalamocortical (TC) axons from VM thalamus excited VM-projecting pyramidal tract (PT) neurons in layer 5B of ALM. These axons also strongly excited layer 2/3 neurons (which strongly excite PT neurons, as previously shown) but not VM-projecting corticothalamic (CT) neurons in layer 6. The strongest connections in the VM → PT circuit were localized to apical tuft dendrites of PT neurons, in layer 1. These tuft inputs were selectively augmented after blocking hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. In thalamus, axons from ALM PT neurons excited ALM-projecting VM neurons, located medially in VM. These axons provided weak input to neurons in mediodorsal nucleus, and little or no input either to neurons in the GABAergic reticular thalamic nucleus or to neurons in VM projecting to primary motor cortex (M1). Conversely, M1 PT axons excited M1-but not ALM-projecting VM neurons. Our findings indicate, first, a set of cell type-specific connections forming an excitatory thalamo-cortico-thalamic loop for ALM ↔ VM communication and a circuit-level substrate for supporting reverberant activity in this system. Second, a key feature of this loop is the prominent involvement of layer 1 synapses onto apical dendrites, a subcellular compartment with distinct signaling properties, including HCN-mediated gain control. Third, the segregation of the ALM ↔ VM loop from M1-related circuits of VM adds cellular-level support for the concept of parallel pathway organization in the motor system.
AB - The anterolateral motor cortex (ALM) and ventral medial (VM) thalamus are functionally linked to support persistent activity during motor planning. We analyzed the underlying synaptic interconnections using optogenetics and electrophysiology in mice (female/male). In cortex, thalamocortical (TC) axons from VM thalamus excited VM-projecting pyramidal tract (PT) neurons in layer 5B of ALM. These axons also strongly excited layer 2/3 neurons (which strongly excite PT neurons, as previously shown) but not VM-projecting corticothalamic (CT) neurons in layer 6. The strongest connections in the VM → PT circuit were localized to apical tuft dendrites of PT neurons, in layer 1. These tuft inputs were selectively augmented after blocking hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. In thalamus, axons from ALM PT neurons excited ALM-projecting VM neurons, located medially in VM. These axons provided weak input to neurons in mediodorsal nucleus, and little or no input either to neurons in the GABAergic reticular thalamic nucleus or to neurons in VM projecting to primary motor cortex (M1). Conversely, M1 PT axons excited M1-but not ALM-projecting VM neurons. Our findings indicate, first, a set of cell type-specific connections forming an excitatory thalamo-cortico-thalamic loop for ALM ↔ VM communication and a circuit-level substrate for supporting reverberant activity in this system. Second, a key feature of this loop is the prominent involvement of layer 1 synapses onto apical dendrites, a subcellular compartment with distinct signaling properties, including HCN-mediated gain control. Third, the segregation of the ALM ↔ VM loop from M1-related circuits of VM adds cellular-level support for the concept of parallel pathway organization in the motor system.
KW - Corticothalamic
KW - Layer 1
KW - Motor cortex
KW - Thalamocortical
KW - Ventromedial thalamus
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U2 - 10.1523/JNEUROSCI.1333-18.2018
DO - 10.1523/JNEUROSCI.1333-18.2018
M3 - Article
C2 - 30143573
AN - SCOPUS:85054740870
VL - 38
SP - 8787
EP - 8797
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 41
ER -