Cortical projections to the thalamus arise from corticothalamic (CT) neurons in layer 6 and pyramidal tract-type (PT) neurons in layer 5B. We dissected the excitatory synaptic connections in the somatosensory thalamus formed by CT and PT neurons of the primary somatosensory (S1) cortex, focusing on mouse forelimb S1. Mice of both sexes were studied. The CT neurons in S1 synaptically excited S1projecting thalamocortical (TC) neurons in subregions of both the ventral posterior lateral and posterior (PO) nuclei, forming a pair of recurrent cortico-thalamo-cortical (C-T-C) loops. The PT neurons in S1 also formed a recurrent loop with S1-projecting TC neurons in the same subregion of the PO. The PT neurons in the adjacent primary motor (M1) cortex formed a separate recurrent loop with M1projecting TC neurons in a nearby subregion of the PO. Collectively, our results reveal that C-T-C circuits of mouse forelimb S1 are primarily organized as multiple cortical cell-type-specific and thalamic subnucleus-specific recurrent loops, with both CT and PT neurons providing the strongest excitatory input to TC neurons that project back to S1. The findings, together with those of related studies of C-T-C circuits, thus suggest that recurrently projecting thalamocortical neurons are the principal targets of cortical excitatory input to the mouse somatosensory and motor thalamus.

Sensory-guided limb control relies on communication across sensorimotor loops. For active touch with the hand, the longest loop is the transcortical continuation of ascending pathways, particularly the lemnisco-cortical and corticocortical pathways carrying tactile signals via the cuneate nucleus, ventral posterior lateral (VPL) thalamus, and primary somatosensory (S1) and motor (M1) cortices to reach corticospinal neurons and influence descending activity. We characterized excitatory connectivity along this pathway in the mouse. In the lemnisco-cortical leg, disynaptic cuneate→VPL→S1 connections excited mainly layer (L) 4 neurons. In the corticocortical leg, S1→M1 connections from L2/3 and L5A neurons mainly excited downstream L2/3 neurons, which excite corticospinal neurons. The findings provide a detailed new wiring diagram for the hand/forelimb-related transcortical circuit, delineating a basic but complex set of cell-type-specific feedforward excitatory connections that selectively and extensively engage diverse intratelencephalic projection neurons, thereby polysynaptically linking subcortical somatosensory input to cortical motor output to spinal cord.

18The small first digit (D1) of the mouse's hand resembles a volar pad, but its thumb-like anatomy 19 suggests ethological importance for manipulating small objects. To explore this possibility, we 20 recorded high-speed close-up video of mice eating seeds and other food items. Analyses of 21 ethograms and automated tracking with DeepLabCut revealed multiple distinct microstructural 22 features of food-handling. First, we found that mice indeed made extensive use of D1 for 23 dexterous manipulations. In particular, mice used D1 to hold food with either of two grip types: a 24 pincer-type grasp, or a "thumb-hold" grip, pressing with D1 from the side. Thumb-holding was 25 preferentially used for handling smaller items, with the smallest items held between the two D1s 26 alone. Second, we observed that mice cycled rapidly between two postural modes while feeding, 27with the hands positioned either at the mouth (oromanual phase) or resting below (holding 28 phase). Third, we identified two highly stereotyped D1-related movements during feeding, 29including an extraordinarily fast (~20 ms) "regrip" maneuver, and a fast (~100 ms) "sniff" 30 maneuver. Lastly, in addition to these characteristic simpler movements and postures, we also 31 observed highly complex movements, including rapid D1-assisted rotations of food items and 32 dexterous simultaneous double-gripping of two food fragments. Manipulation behaviors were 33 generally conserved for different food types, and for head-fixed mice. Wild squirrels displayed a 34 similar repertoire of D1-related movements. Our results define, for the mouse, a set of kinematic 35 building-blocks of manual dexterity, and reveal an outsized role for D1 in these actions. 36 37 focused on observing food-handling by mice that were unrestrained, moving and feeding freely 61 within a small chamber. Because head-fixation is an important methodology that enables neural 62 recording and stimulation to elucidate mechanisms of forelimb motor control in mice (e.g. 63 [17,20,21]), in a subset of experiments we extended these studies to head-fixed mice. 64Additionally, because the findings suggested similarities as well as differences with the 65 previously reported thumb-holding behavior of squirrels [12], in a limited set of field studies we 66 analyzed videos of wild squirrels handling food. Overall, our results reveal extensive use of the 67 thumb and provide new insights into fundamental aspects of food-handling behavior by mice. 68 69 Results 70Mice use their thumbs to handle food 71 The C57BL/6 mouse possesses a pentadactyl manus with a small D1, longer D2-D5 72 digits, and multiple digital and volar pads, as observed by micro-CT and macroscopy (Fig 1). 73The D1 digital and thenar pads are close together, separated by a crease-like cleft, and D1 has a 74 flat nail (Fig 1C, inset). 75 76 (F) Fraction of grips that were thumb-holds for millet, couscous, and black-eyed peas, showing 129 the dependence of grip type on seed size. Gray lines: medians for each mouse (n = 7); purple: 130 median...

The small first digit (D1) of the mouse's hand resembles a volar pad, but its thumb-like anatomy suggests ethological importance for manipulating small objects. To explore this possibility, we recorded high-speed close-up video of mice eating seeds and other food items. Analyses of ethograms and automated tracking with DeepLabCut revealed multiple distinct microstructural features of food-handling. First, we found that mice indeed made extensive use of D1 for dexterous manipulations. In particular, mice used D1 to hold food with either of two grip types: a pincer-type grasp, or a "thumb-hold" grip, pressing with D1 from the side. Thumb-holding was preferentially used for handling smaller items, with the smallest items held between the two D1s alone. Second, we observed that mice cycled rapidly between two postural modes while feeding, with the hands positioned either at the mouth (oromanual phase) or resting below (holding phase). Third, we identified two highly stereotyped D1related movements during feeding, including an extraordinarily fast (~20 ms) "regrip" maneuver, and a fast (~100 ms) "sniff" maneuver. Lastly, in addition to these characteristic simpler movements and postures, we also observed highly complex movements, including rapid D1-assisted rotations of food items and dexterous simultaneous double-gripping of two food fragments. Manipulation behaviors were generally conserved for different food types, and for head-fixed mice. Wild squirrels displayed a similar repertoire of D1-related movements. Our results define, for the mouse, a set of kinematic building-blocks of manual dexterity, and reveal an outsized role for D1 in these actions. OPEN ACCESSCitation: Barrett JM, Raineri Tapies MG, Shepherd GMG (2020) Manual dexterity of mice during foodhandling involves the thumb and a set of fast basic movements. PLoS ONE 15(1): e0226774. https://

Sensory-guided limb control relies on communication across sensorimotor loops. For active touch with the hand, the longest loop is the transcortical continuation of ascending pathways, particularly the lemnisco-cortical and corticocortical pathways carrying tactile signals via the cuneate nucleus, ventral posterior lateral (VPL) thalamus, and primary somatosensory (S1) and motor (M1) cortices to reach corticospinal neurons and influence descending activity. We characterized excitatory connectivity along this pathway in the mouse. In the lemnisco-cortical leg, disynaptic cuneate→VPL→S1 connections excited mainly layer (L) 4 neurons. In the corticocortical leg, S1→M1 connections from L2/3 and L5A neurons mainly excited downstream L2/3 neurons, which excite corticospinal neurons. The findings provide a detailed new wiring diagram for the hand/forelimb-related transcortical circuit, delineating a basic but complex set of cell-type-specific feedforward excitatory connections that selectively and extensively engage diverse intratelencephalic projection neurons, thereby polysynaptically linking subcortical somatosensory input to cortical motor output to spinal cord.