Nature - USA (2020-01-16)

388 | Nature | Vol 577 | 16 January 2020

Article

a b Neural trajectory, post-laser

reach vs no reach

Hand trajectory, post-laser

reach vs no reach

–500 ms Laser end +500

0 mm

20

40

–500 ms Laser end +500

0 AU

12

Laser Laser

Spatial distance from hand to target Neural distance to target

ReachNo reach ReachNo reach

c

Schematic: a post-laser difference between

reach and no reach activity implies a difference in input

d

e

–200 ms Laser end +200

Laser

PC 1

PC 2PC 3

0 AU

–100

100

Estimated difference in inputs,

reach – no reach

Motor cortex, dimension 2Motor cortex, dimension 1

u(t)

h(r(t))

Laser on

Reach

No reach

Dif

ference in inputs (AU)

PC 3PC 1

PC 2

Up (5 mm)ForwarRightd

Laser on

Reach

Lift No reach

Hand open

At mouthGrab Reach

No reach

Fig. 2 | Divergence of neural trajectories from the same initial state.
a, Average hand trajectory for trials with (blue) and without (red) post-laser
reaches in VGAT-ChR2-eYFP mice (n = 4 mice and n = 6 sessions). b, Neural
population activity aligned to the end of the laser for trials with (blue) and
without (red) a post-laser reach (n = 128 neurons). Time limits are 250 ms before
the end of the laser to 250 ms after the end of the laser. Black dot indicates
baseline activity before the start of the trial. c, Spatial (left) and neural (right)

distance to target, centred on the end of the laser, for trials with (blue) and

without (red) post-laser reaches. d, Schematic illustrating that a divergence in

neural trajectories from the same initial state implies a difference in external

inputs. e, Estimated difference in external inputs between reach and no-reach

conditions (see Methods). The divergence of the traces shortly before the end

of the laser is owing to smoothing (Extended Data Fig. 5a–d).

Prob. lift, 0–500 ms 0

(^1) Ctrl
Thal.
laser
a
Thal. Cortex
b
0 s2 4
Lift time pr
obability
0
0.4
Laser
(thal.)
c
Hand position (up)
10 mm
–0.5 sLift 123
Control
Laser (thal.)
Control
Lift time distribution,
control and thal. laser
Hand trajectories,
control and mid-reach thal. laser
PC 3PC
PC^21
Laser-end-aligned neural trajectories,
ctx laser vs ctx laser, then thal. laser
0 s2Laser 46
(thal.)
Laser
(ctx) Laser (thal.)
–2
6
Ctx
silenced
Laser (ctx) 500 ms
Firing rate (
z-score
)
Laser (ctx)
Lift time pr
obability
0
0.4
Lift time distribution, control,
ctx laser, and ctx, then thal. laser
500 ms
Firing rates, ctx laser Firing rates, ctx laser, then thal. laser
Schematic: a divergence between
release ctx and release ctx, silence thal.
implies a difference in inputs
Motor cortex, dimension 2Motor cortex, dimension 1
Release ctx,silence thal. Release ctx
u(t)
Cortex silenced
–200 ms Laser end +200
PC 1
PC 2PC 3
0
–150
150
Dif
ference in inputs (AU)
Estimated difference in inputs,
release ctx – release ctx, silence thal.
Laser (cortex)
de
f g h
h(r(t))
Release
thal. ( )
Release ctx ( )
Release ctx,
silence thal. ( )
Fig. 3 | External inputs are required for the motor cortical pattern during
reaching. a, Experimental schematic. Placement of fibres over motor cortex
and thalamus (thal). b, Distribution of lift times on control (yellow) and
thalamic inactivation (green) trials; n = 3 mice (VGAT-ChR2-eYFP) and n = 7
sessions. Right inset shows the probability of a lift within the first 500 ms
following the cue for control and thalamus inactivation trials. c, Hand position
in the upper direction centred on lift on control trials (light yellow) and mid-
reach thalamic inactivation trials (black; green indicates laser on) for a single
dataset. Dots indicate the start of the laser. Data from all mice (n = 4 mice and
n = 6 sessions) are shown in Extended Data Fig. 6. d, Lift times for control trials
(yellow), cortical inactivation (blue) and sequential inactivation of cortex
(ctx) and thalamus (green); n = 3 mice (VGAT-ChR2-eYFP) and n = 4 sessions.
e, Average firing rate z-scores for all recorded neurons under inactivation of
cortex alone (left) and sequential inactivation of cortex and thalamus (right);
n = 3 mice, n = 4 sessions and n = 127 neurons. f, Population activity following
the end of cortical inactivation for trials with cortical inactivation only (blue)
and inactivation of thalamus after cortex (green). Plotting limits start 500 ms
before the end of cortical inactivation and finish 500 ms after the cortical
inactivation (blue trace) and 500 ms after the thalamic inactivation (green
trace). The divergence of the trajectories shortly before the end of cortical
inactivation results from smoothing (Extended Data Fig. 5e–h), and inhibitory
interneurons were excluded. g, Schematic illustrating that the divergence from
the cortex-inactivated state reveals differences in input. h, Estimated
difference in external inputs following the end of cortical inactivation between
thalamus inactivated (u−th(t)) and not inactivated (u+th(t)) conditions. The
difference is given by u+th(t) – u−th(t).